Recurrent Moderate Hypoglycemia Suppresses Brain-Derived Neurotrophic Factor Expression in the Prefrontal Cortex and Impairs Sensorimotor Gating in the Post-Hypoglycemia Period in Young Rats

PubMed Central

Rao, Raghavendra; Ennis, Kathleen; Mitchell, Eugena P.; Tran, Phu V.; Gewirtz, Jonathan C.

2016-01-01

Recurrent hypoglycemia is common in infants and children. In developing rat models, recurrent moderate hypoglycemia leads to neuronal injury in the medial prefrontal cortex. To understand the effects beyond neuronal injury, three-week-old male rats were subjected to five episodes of moderate hypoglycemia (blood glucose concentration, approximately 30 mg/dl for 90 min) once daily from postnatal day 24 to 28. Neuronal injury was determined using Fluoro-jade B histochemistry on postnatal day 29. The effects on brain-derived neurotrophic factor (BDNF) and its cognate receptor, tyrosine kinase B (TrkB) expression, which is critical for prefrontal cortex development, were determined on postnatal day 29 and at adulthood. The effects on prefrontal cortex-mediated function were determined by assessing prepulse inhibition of the acoustic startle reflex on postnatal day 29 and two weeks later, and by testing for fear-potentiated startle at adulthood. Recurrent hypoglycemia led to neuronal injury confined primarily to the medial prefrontal cortex. BDNF and TrkB expression in the prefrontal cortex was suppressed on postnatal day 29 and was accompanied by lower prepulse inhibition, suggesting impaired sensorimotor gating. Following the cessation of recurrent hypoglycemia, prepulse inhibition had recovered at two weeks. BDNF/TrkB expression in the prefrontal cortex had normalized and fear-potentiated startle was intact at adulthood. Recurrent moderate hypoglycemia during development has significant adverse effects on the prefrontal cortex in the post-hypoglycemia period. PMID:26820887

Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers

PubMed Central

Quednow, Boris B; Kometer, Michael; Geyer, Mark A; Vollenweider, Franz X

2012-01-01

The serotonin-2A receptor (5-HT2AR) has been implicated in the pathogenesis of schizophrenia and related inhibitory gating and behavioral inhibition deficits of schizophrenia patients. The hallucinogen psilocybin disrupts automatic forms of sensorimotor gating and response inhibition in humans, but it is unclear so far whether the 5-HT2AR or 5-HT1AR agonist properties of its bioactive metabolite psilocin account for these effects. Thus, we investigated whether psilocybin-induced deficits in automatic and controlled inhibition in healthy humans could be attenuated by the 5-HT2A/2CR antagonist ketanserin. A total of 16 healthy participants received placebo, ketanserin (40 mg p.o.), psilocybin (260 μg/kg p.o.), or psilocybin plus ketanserin in a double-blind, randomized, and counterbalanced order. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response. The effects on psychopathological core dimensions and behavioral inhibition were assessed by the altered states of consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test. Psilocybin decreased PPI at short lead intervals (30 ms), increased all 5D-ASC scores, and selectively increased errors in the interference condition of the Stroop Test. Stroop interference and Stroop effect of the response latencies were increased under psilocybin as well. Psilocybin-induced alterations were attenuated by ketanserin pretreatment, whereas ketanserin alone had no significant effects. These findings suggest that the disrupting effects of psilocybin on automatic and controlled inhibition processes are attributable to 5-HT2AR stimulation. Sensorimotor gating and attentional control deficits of schizophrenia patients might be due to changes within the 5-HT2AR system. PMID:21956447

Psilocybin-induced deficits in automatic and controlled inhibition are attenuated by ketanserin in healthy human volunteers.

PubMed

Quednow, Boris B; Kometer, Michael; Geyer, Mark A; Vollenweider, Franz X

2012-02-01

The serotonin-2A receptor (5-HT(2A)R) has been implicated in the pathogenesis of schizophrenia and related inhibitory gating and behavioral inhibition deficits of schizophrenia patients. The hallucinogen psilocybin disrupts automatic forms of sensorimotor gating and response inhibition in humans, but it is unclear so far whether the 5-HT(2A)R or 5-HT(1A)R agonist properties of its bioactive metabolite psilocin account for these effects. Thus, we investigated whether psilocybin-induced deficits in automatic and controlled inhibition in healthy humans could be attenuated by the 5-HT(2A/2C)R antagonist ketanserin. A total of 16 healthy participants received placebo, ketanserin (40 mg p.o.), psilocybin (260 μg/kg p.o.), or psilocybin plus ketanserin in a double-blind, randomized, and counterbalanced order. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response. The effects on psychopathological core dimensions and behavioral inhibition were assessed by the altered states of consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test. Psilocybin decreased PPI at short lead intervals (30 ms), increased all 5D-ASC scores, and selectively increased errors in the interference condition of the Stroop Test. Stroop interference and Stroop effect of the response latencies were increased under psilocybin as well. Psilocybin-induced alterations were attenuated by ketanserin pretreatment, whereas ketanserin alone had no significant effects. These findings suggest that the disrupting effects of psilocybin on automatic and controlled inhibition processes are attributable to 5-HT(2A)R stimulation. Sensorimotor gating and attentional control deficits of schizophrenia patients might be due to changes within the 5-HT(2A)R system.

A predictive processing theory of sensorimotor contingencies: Explaining the puzzle of perceptual presence and its absence in synesthesia.

PubMed

Seth, Anil K

2014-01-01

Normal perception involves experiencing objects within perceptual scenes as real, as existing in the world. This property of "perceptual presence" has motivated "sensorimotor theories" which understand perception to involve the mastery of sensorimotor contingencies. However, the mechanistic basis of sensorimotor contingencies and their mastery has remained unclear. Sensorimotor theory also struggles to explain instances of perception, such as synesthesia, that appear to lack perceptual presence and for which relevant sensorimotor contingencies are difficult to identify. On alternative "predictive processing" theories, perceptual content emerges from probabilistic inference on the external causes of sensory signals, however, this view has addressed neither the problem of perceptual presence nor synesthesia. Here, I describe a theory of predictive perception of sensorimotor contingencies which (1) accounts for perceptual presence in normal perception, as well as its absence in synesthesia, and (2) operationalizes the notion of sensorimotor contingencies and their mastery. The core idea is that generative models underlying perception incorporate explicitly counterfactual elements related to how sensory inputs would change on the basis of a broad repertoire of possible actions, even if those actions are not performed. These "counterfactually-rich" generative models encode sensorimotor contingencies related to repertoires of sensorimotor dependencies, with counterfactual richness determining the degree of perceptual presence associated with a stimulus. While the generative models underlying normal perception are typically counterfactually rich (reflecting a large repertoire of possible sensorimotor dependencies), those underlying synesthetic concurrents are hypothesized to be counterfactually poor. In addition to accounting for the phenomenology of synesthesia, the theory naturally accommodates phenomenological differences between a range of experiential states including dreaming, hallucination, and the like. It may also lead to a new view of the (in)determinacy of normal perception.

A predictive processing theory of sensorimotor contingencies: Explaining the puzzle of perceptual presence and its absence in synesthesia

PubMed Central

Seth, Anil K.

2014-01-01

Normal perception involves experiencing objects within perceptual scenes as real, as existing in the world. This property of “perceptual presence” has motivated “sensorimotor theories” which understand perception to involve the mastery of sensorimotor contingencies. However, the mechanistic basis of sensorimotor contingencies and their mastery has remained unclear. Sensorimotor theory also struggles to explain instances of perception, such as synesthesia, that appear to lack perceptual presence and for which relevant sensorimotor contingencies are difficult to identify. On alternative “predictive processing” theories, perceptual content emerges from probabilistic inference on the external causes of sensory signals, however, this view has addressed neither the problem of perceptual presence nor synesthesia. Here, I describe a theory of predictive perception of sensorimotor contingencies which (1) accounts for perceptual presence in normal perception, as well as its absence in synesthesia, and (2) operationalizes the notion of sensorimotor contingencies and their mastery. The core idea is that generative models underlying perception incorporate explicitly counterfactual elements related to how sensory inputs would change on the basis of a broad repertoire of possible actions, even if those actions are not performed. These “counterfactually-rich” generative models encode sensorimotor contingencies related to repertoires of sensorimotor dependencies, with counterfactual richness determining the degree of perceptual presence associated with a stimulus. While the generative models underlying normal perception are typically counterfactually rich (reflecting a large repertoire of possible sensorimotor dependencies), those underlying synesthetic concurrents are hypothesized to be counterfactually poor. In addition to accounting for the phenomenology of synesthesia, the theory naturally accommodates phenomenological differences between a range of experiential states including dreaming, hallucination, and the like. It may also lead to a new view of the (in)determinacy of normal perception. PMID:24446823

Sensorimotor gating characteristics of violent men with comorbid psychosis and dissocial personality disorder: Relationship with antisocial traits and psychosocial deprivation.

PubMed

Sedgwick, Ottilie; Young, Susan; Greer, Ben; Arnold, Jack; Parsons, Aisling; Puzzo, Ignazio; Terracciano, Mariafatima; Das, Mrigendra; Kumari, Veena

2017-07-06

Evidence suggests violence amongst those with psychosis is not aetiologically homogeneous, and that a large proportion of those who engage in violent behaviour have a comorbid antisocial personality disorder. Initial investigations indicate that this subgroup has distinct historical and neuropsychological characteristics, which may indicate diverse treatment needs. This study investigated sensorimotor gating characteristics of violent men with diagnoses of both psychosis and dissocial personality disorder (DPD) (n=21) relative to violent men with psychosis alone (n=12), DPD alone (n=14) and healthy, non-violent male controls (n=27), using the prepulse inhibition (PPI) paradigm. The results indicated that, relative to the psychosis alone and healthy control groups, the comorbid group had lower PPI, especially at 60-ms prepulse-to-pulse interval. The DPD group took an intermediary position and did not differ from any group. Antisocial personality traits (factor two scores of the Psychopathy Checklist - Revised), and greater severity of childhood psychosocial deprivation (including physical and sexual abuse), were significantly correlated with poor PPI across the clinical sample. The findings suggest diverse sensorimotor gating profiles amongst subgroups of violent offenders, with comorbid psychosis and DPD showing most impairment. This is consistent with a 'double dose' of deficit explanation amongst those with both diagnoses, explained at least in part by presence of antisocial personality traits and childhood psychosocial deprivation. Copyright © 2017 Elsevier B.V. All rights reserved.

Knockdown of phospholipase C-β1 in the medial prefrontal cortex of male mice impairs working memory among multiple schizophrenia endophenotypes

PubMed Central

Kim, Seong-Wook; Seo, Misun; Kim, Duk-Soo; Kang, Moonkyung; Kim, Yeon-Soo; Koh, Hae-Young; Shin, Hee-Sup

2015-01-01

Background Decreased expression of phospholipase C-β1 (PLC-β1) has been observed in the brains of patients with schizophrenia, but, to our knowledge, no studies have shown a possible association between this altered PLC-β1 expression and the pathogenesis of schizophrenia. Although PLC-β1-null (PLC-β1−/−) mice exhibit multiple endophenotypes of schizophrenia, it remains unclear how regional decreases in PLC-β1 expression in the brain contribute to specific behavioural defects. Methods We selectively knocked down PLC-β1 in the medial prefrontal cortex (mPFC) using a small hairpin RNA strategy in mice. Results Silencing PLC-β1 in the mPFC resulted in working memory deficits, as assayed using the delayed non-match-to-sample T-maze task. Notably, however, other schizophrenia- related behaviours observed in PLC-β1−/− mice, including phenotypes related to locomotor activity, sociability and sensorimotor gating, were normal in PLC-β1 knockdown mice. Limitations Phenotypes of PLC-β1 knockdown mice, such as locomotion, anxiety and sensorimotor gating, have already been published in our previous studies. Further, the neural mechanisms underlying the working memory deficit in mice may be different from those in human schizophrenia. Conclusion These results indicate that PLC-β1 signalling in the mPFC is required for working memory. Importantly, these results support the notion that the decrease in PLC-β1 expression in the brains of patients with schizophrenia is a pathogenically relevant molecular marker of the disorder. PMID:25268789

Sensorimotor gating impairments induced by MK-801 treatment may be reduced by tolerance effect and by familiarization in monkeys

PubMed Central

Saletti, Patricia G.; Maior, Rafael S.; Hori, Etsuro; Nishijo, Hisao; Tomaz, Carlos

2015-01-01

Dizocilpine (MK-801) is a non-competitive NMDA antagonist that induces schizophreniclike effects. It is therefore widely used in experimental models of schizophrenia including prepulse inhibition (PPI) impairments in rodents. Nevertheless, MK-801 has never been tested in monkeys on a PPI paradigm. In order to evaluate MK-801 effects on monkeys’ PPI, we tested eight capuchin monkeys (Sapajus spp.) using three different doses of MK-801 (0.01; 0.02; 0.03 mg/kg). Results show PPI impairment in acute administration of the highest dose (0.03 mg/kg). PPI impairment induced by MK-801 was reversed by re-exposure to the PPI test throughout treatment trials, in contrast with rodent studies. These results indicate that tolerance effect and familiarization with PPI test may reduce the sensorimotor gating deficits induced by MK-801 in monkeys, suggesting a drug-training interaction. PMID:26441660

Prenatal Immune Challenge Is an Environmental Risk Factor for Brain and Behavior Change Relevant to Schizophrenia: Evidence from MRI in a Mouse Model

PubMed Central

Wei, Ran; Hui, Edward S.; Feldon, Joram; Meyer, Urs; Chung, Sookja; Chua, Siew E.; Sham, Pak C.; Wu, Ed X.; McAlonan, Grainne M.

2009-01-01

Objectives Maternal infection during pregnancy increases risk of severe neuropsychiatric disorders, including schizophrenia and autism, in the offspring. The most consistent brain structural abnormality in patients with schizophrenia is enlarged lateral ventricles. However, it is unknown whether the aetiology of ventriculomegaly in schizophrenia involves prenatal infectious processes. The present experiments tested the hypothesis that there is a causal relationship between prenatal immune challenge and emergence of ventricular abnormalities relevant to schizophrenia in adulthood. Method We used an established mouse model of maternal immune activation (MIA) by the viral mimic PolyI:C administered in early (day 9) or late (day 17) gestation. Automated voxel-based morphometry mapped cerebrospinal fluid across the whole brain of adult offspring and the results were validated by manual region-of-interest tracing of the lateral ventricles. Parallel behavioral testing determined the existence of schizophrenia-related sensorimotor gating abnormalities. Results PolyI:C-induced immune activation, in early but not late gestation, caused marked enlargement of lateral ventricles in adulthood, without affecting total white and grey matter volumes. This early exposure disrupted sensorimotor gating, in the form of prepulse inhibition. Identical immune challenge in late gestation resulted in significant expansion of 4th ventricle volume but did not disrupt sensorimotor gating. Conclusions Our results provide the first experimental evidence that prenatal immune activation is an environmental risk factor for adult ventricular enlargement relevant to schizophrenia. The data indicate immune-associated environmental insults targeting early foetal development may have more extensive neurodevelopmental impact than identical insults in late prenatal life. PMID:19629183

Memantine Effects On Sensorimotor Gating and Mismatch Negativity in Patients with Chronic Psychosis.

PubMed

Swerdlow, Neal R; Bhakta, Savita; Chou, Hsun-Hua; Talledo, Jo A; Balvaneda, Bryan; Light, Gregory A

2016-01-01

Patients with chronic psychotic disorders (CPD) exhibit deficient sensorimotor gating (measured by prepulse inhibition (PPI) of startle) and mismatch negativity (MMN). In healthy subjects (HS), N-methyl-D-aspartate (NMDA) antagonists like memantine and ketamine increase PPI, and under some conditions, memantine enhances MMN; these findings present a challenge to understanding the basis for deficient PPI and MMN in psychotic disorders, as reduced NMDA activity is implicated in the pathogenesis of these disorders. Here we assessed for the first time the effects of memantine on PPI and MMN in CPD subjects. Baseline PPI was measured in HS and patients with a diagnosis of schizophrenia or schizoaffective disorder, depressed type. Subjects (total n=84) were then tested twice, in a double-blind crossover design, comparing either: (1) placebo vs 10 mg of memantine or (2) placebo vs 20 mg memantine. Tests included measures of acoustic startle magnitude and habituation, PPI, MMN, autonomic indices, and subjective self-rating scales. Memantine (20 mg) significantly enhanced PPI in CPD subjects, and enhanced MMN across subject groups. These effects on PPI were age dependent and most evident in older CPD patients, whereas those on MMN were most evident in younger subjects. The lower dose (10 mg) either had no detectable effect or tended to degrade these measures. The NMDA antagonist, memantine, has dose-dependent effects on preconscious, automatic measures of sensorimotor gating and auditory sensory processing that are associated with enhanced cognition and function in CPD patients. Ongoing studies will determine whether these memantine-induced changes predict acute pro-cognitive or otherwise clinically beneficial effects in CPD patients.

Sensorimotor Gating in Depressed and Euthymic Patients with Bipolar Disorder: Analysis on Prepulse Inhibition of Acoustic Startle Response Stratified by Gender and State.

PubMed

Matsuo, Junko; Ota, Miho; Hidese, Shinsuke; Teraishi, Toshiya; Hori, Hiroaki; Ishida, Ikki; Hiraishi, Moeko; Kunugi, Hiroshi

2018-01-01

Prepulse inhibition (PPI) of the acoustic startle reflex is an operational measure of sensorimotor gating. The findings on PPI deficits in bipolar disorder (BD) are inconsistent among studies due to various confounding factors such as gender. This study aimed to assess sensorimotor gating deficits in patients with BD stratified by gender and state (depressed/euthymic), and to explore related clinical variables. Subjects were 106 non-manic BD patients (26 BD I and 80 BD II; 63 with depression and 43 euthymic) and 232 age-, gender-, and ethnicity-matched (Japanese) healthy controls. Depression severity was assessed using the Hamilton Depression Rating Scale-21. The electromyographic activity of the orbicularis oculi muscle was measured by a computerized startle reflex test unit. Startle magnitude, habituation, and PPI were compared among the three clinical groups: depressed BD, euthymic BD, and healthy controls. In a second analysis, patients were divided into four groups using the quartile PPI levels of controls of each gender, and a ratio of the low-PPI group (<1st quartile of controls) was compared. Effects of psychosis and medication status were examined by the Mann-Whitney U test. Clinical correlates such as medication dosage and depression severity with startle measurements were examined by Spearman's correlation. Male patients with depression, but not euthymic male patients, showed significantly lower PPI at a prepulse of 86 dB and 120 ms lead interval than did male controls. More than half of the male patients with depression showed low-PPI. In contrast, PPI in female patients did not differ from that in female controls in either the depressed or euthymic state. Female patients with active psychosis showed significantly lower PPI than those without psychosis. Female patients on typical antipsychotics had significantly lower PPI, than those without such medication. PPI showed a significant positive correlation with lamotrigine dosage in male patients and lithium dosage in female patients. These findings suggest that sensorimotor gating is impaired in male BD patients with depression. However, we obtained no evidence for such abnormalities in female BD patients except for those with current psychosis. The observed associations between medication and startle measurements warrant further investigation.

Reduced Structural Connectivity in Frontostriatal White Matter Tracts in the Associative Loop in Schizophrenia.

PubMed

Levitt, James J; Nestor, Paul G; Levin, Laura; Pelavin, Paula; Lin, Pan; Kubicki, Marek; McCarley, Robert W; Shenton, Martha E; Rathi, Yogesh

2017-11-01

The striatum receives segregated and integrative white matter tracts from the cortex facilitating information processing in the cortico-basal ganglia network. The authors examined both types of input tracts in the striatal associative loop in chronic schizophrenia patients and healthy control subjects. Structural and diffusion MRI scans were acquired on a 3-T system from 26 chronic schizophrenia patients and 26 matched healthy control subjects. Using FreeSurfer, the associative cortex was parcellated into ventrolateral prefrontal cortex and dorsolateral prefrontal cortex subregions. The striatum was manually parcellated into its associative and sensorimotor functional subregions. Fractional anisotropy and normalized streamlines, an estimate of fiber counts, were assessed in four frontostriatal tracts (dorsolateral prefrontal cortex-associative striatum, dorsolateral prefrontal cortex-sensorimotor striatum, ventrolateral prefrontal cortex-associative striatum, and ventrolateral prefrontal cortex-sensorimotor striatum). Furthermore, these measures were correlated with a measure of cognitive control, the Trail-Making Test, Part B. Results showed reduced fractional anisotropy and fewer streamlines in chronic schizophrenia patients for all four tracts, both segregated and integrative. Post hoc t tests showed reduced fractional anisotropy in the left ventrolateral prefrontal cortex-associative striatum and left ventrolateral prefrontal cortex-sensorimotor striatum and fewer normalized streamlines in the right dorsolateral prefrontal cortex-sensorimotor striatum and in the left and right ventrolateral prefrontal cortex-sensorimotor striatum in chronic schizophrenia patients. Furthermore, normalized streamlines in the right dorsolateral prefrontal cortex-sensorimotor striatum negatively correlated with Trail-Making Test, Part B, time spent in healthy control subjects but not in chronic schizophrenia patients. These findings demonstrated that structural connectivity is reduced in both segregated and integrative tracts in the striatal associative loop in chronic schizophrenia and that reduced normalized streamlines in the right-hemisphere dorsolateral prefrontal cortex-sensorimotor striatum predicted worse cognitive control in healthy control subjects but not in chronic schizophrenia patients, suggesting a loss of a "normal" brain-behavior correlation in chronic schizophrenia.

Assessment of Motor Function, Sensory Motor Gating and Recognition Memory in a Novel BACHD Transgenic Rat Model for Huntington Disease

PubMed Central

Abada, Yah-se K.; Nguyen, Huu Phuc; Schreiber, Rudy; Ellenbroek, Bart

2013-01-01

Rationale Huntington disease (HD) is frequently first diagnosed by the appearance of motor symptoms; the diagnosis is subsequently confirmed by the presence of expanded CAG repeats (> 35) in the HUNTINGTIN (HTT) gene. A BACHD rat model for HD carrying the human full length mutated HTT with 97 CAG-CAA repeats has been established recently. Behavioral phenotyping of BACHD rats will help to determine the validity of this model and its potential use in preclinical drug discovery studies. Objectives The present study seeks to characterize the progressive emergence of motor, sensorimotor and cognitive deficits in BACHD rats. Materials and Methods Wild type and transgenic rats were tested from 1 till 12 months of age. Motor tests were selected to measure spontaneous locomotor activity (open field) and gait coordination. Sensorimotor gating was assessed in acoustic startle response paradigms and recognition memory was evaluated in an object recognition test. Results Transgenic rats showed hyperactivity at 1 month and hypoactivity starting at 4 months of age. Motor coordination imbalance in a Rotarod test was present at 2 months and gait abnormalities were seen in a Catwalk test at 12 months. Subtle sensorimotor changes were observed, whereas object recognition was unimpaired in BACHD rats up to 12 months of age. Conclusion The current BACHD rat model recapitulates certain symptoms from HD patients, especially the marked motor deficits. A subtle neuropsychological phenotype was found and further studies are needed to fully address the sensorimotor phenotype and the potential use of BACHD rats for drug discovery purposes. PMID:23874679

Maslinic acid ameliorates NMDA receptor blockade-induced schizophrenia-like behaviors in mice.

PubMed

Jeon, Se Jin; Kim, Eunji; Lee, Jin Su; Oh, Hee Kyong; Zhang, Jiabao; Kwon, Yubeen; Jang, Dae Sik; Ryu, Jong Hoon

2017-11-01

Schizophrenia is a chronic psychotic disorder characterized by positive, negative, and cognitive symptoms. Primary treatments for schizophrenia relieve the positive symptoms but are less effective against the negative and cognitive symptoms. In the present study, we investigated whether maslinic acid, isolated from Syzygium aromaticum (clove), can ameliorate schizophrenia-like behaviors in mice induced by MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist. After maslinic acid treatment in the MK-801 model, we examined the behavioral alteration and signaling pathways in the prefrontal cortex. Mice were treated with maslinic acid (30 mg/kg), and their behaviors were evaluated through an array of behavioral tests. The effects of maslinic acid were also examined in the signaling pathways in the prefrontal cortex. A single administration of maslinic acid blocked the MK-801-induced hyperlocomotion and reversed the MK-801-induced sensorimotor gating deficit in the acoustic startle response test. In the social novelty preference test, maslinic acid ameliorated the social behavior deficits induced by MK-801. The MK-801-induced attention and recognition memory impairments were also alleviated by a single administration of maslinic acid. Furthermore, maslinic acid normalized the phosphorylation levels of Akt-GSK-3β and ERK-CREB in the prefrontal cortex. Overall, maslinic acid ameliorated the schizophrenia-like symptoms induced by MK-801, and these effects may be partly mediated through Akt-GSK-3β and ERK-CREB activation. These findings suggest that maslinic acid could be a candidate for the treatment of several symptoms of schizophrenia, including positive symptoms, sensorimotor gating disruption, social interaction deficits, and cognitive impairments. Copyright © 2017 Elsevier Ltd. All rights reserved.

THE REELIN RECEPTORS VLDLR AND ApoER2 REGULATE SENSORIMOTOR GATING IN MICE

PubMed Central

Barr, Alasdair M.; Fish, Kenneth N.; Markou, Athina

2007-01-01

Summary Postmortem brain loss of reelin is noted in schizophrenia patients. Accordingly, heterozygous reeler mutant mice have been proposed as a putative model of this disorder. Little is known, however, about the involvement of the two receptors for reelin, Very-Low-Density Lipoprotein Receptor (VLDLR) and Apolipoprotein E Receptor 2 (ApoER2), on pre-cognitive processes of relevance to deficits seen in schizophrenia. Thus, we evaluated sensorimotor gating in mutant mice heterozygous or homozygous for the two reelin receptors. Mutant mice lacking one of these reelin receptors were tested for prepulse inhibition (PPI) of the acoustic startle reflex prior to and following puberty, and on a crossmodal PPI task, involving the presentation of acoustic and tactile stimuli. Furthermore, because schizophrenia patients show increased sensitivity to N-methyl-D-aspartate (NMDA) receptor blockade, we assessed the sensitivity of these mice to the PPI-disruptive effects of the NMDA receptor antagonist phencyclidine. The results demonstrated that acoustic PPI did not differ between mutant and wildtype mice. However, VLDLR homozygous mice displayed significant deficits in crossmodal PPI, while ApoER2 heterozygous and homozygous mice displayed significantly increased crossmodal PPI. Both ApoER2 and VLDLR heterozygous and homozygous mice exhibited greater sensitivity to the PPI-disruptive effects of phencyclidine than wildtype mice. These results indicate that partial or complete loss of either one of the reelin receptors results in a complex pattern of alterations in PPI function that include alterations in crossmodal, but not acoustic, PPI and increased sensitivity to NMDA receptor blockade. Thus, reelin receptor function appears to be critically involved in crossmodal PPI and the modulation of the PPI response by NMDA receptors. These findings have relevance to a range of neuropsychiatric disorders that involve sensorimotor gating deficits, including schizophrenia.. PMID:17261317

Memantine Effects On Sensorimotor Gating and Mismatch Negativity in Patients with Chronic Psychosis

PubMed Central

Swerdlow, Neal R; Bhakta, Savita; Chou, Hsun-Hua; Talledo, Jo A; Balvaneda, Bryan; Light, Gregory A

2016-01-01

Patients with chronic psychotic disorders (CPD) exhibit deficient sensorimotor gating (measured by prepulse inhibition (PPI) of startle) and mismatch negativity (MMN). In healthy subjects (HS), N-methyl-D-aspartate (NMDA) antagonists like memantine and ketamine increase PPI, and under some conditions, memantine enhances MMN; these findings present a challenge to understanding the basis for deficient PPI and MMN in psychotic disorders, as reduced NMDA activity is implicated in the pathogenesis of these disorders. Here we assessed for the first time the effects of memantine on PPI and MMN in CPD subjects. Baseline PPI was measured in HS and patients with a diagnosis of schizophrenia or schizoaffective disorder, depressed type. Subjects (total n=84) were then tested twice, in a double-blind crossover design, comparing either: (1) placebo vs 10 mg of memantine or (2) placebo vs 20 mg memantine. Tests included measures of acoustic startle magnitude and habituation, PPI, MMN, autonomic indices, and subjective self-rating scales. Memantine (20 mg) significantly enhanced PPI in CPD subjects, and enhanced MMN across subject groups. These effects on PPI were age dependent and most evident in older CPD patients, whereas those on MMN were most evident in younger subjects. The lower dose (10 mg) either had no detectable effect or tended to degrade these measures. The NMDA antagonist, memantine, has dose-dependent effects on preconscious, automatic measures of sensorimotor gating and auditory sensory processing that are associated with enhanced cognition and function in CPD patients. Ongoing studies will determine whether these memantine-induced changes predict acute pro-cognitive or otherwise clinically beneficial effects in CPD patients. PMID:26062785

Ultrasonic vocalizations, predictability and sensorimotor gating in the rat

PubMed Central

Webber, Emily S.; Mankin, David E.; McGraw, Justin J.; Beckwith, Travis J.; Cromwell, Howard C.

2013-01-01

Prepulse inhibition (PPI) is a measure of sensorimotor gating in diverse groups of animals including humans. Emotional states can influence PPI in humans both in typical subjects and in individuals with mental illness. Little is known about emotional regulation during PPI in rodents. We used ultrasonic vocalization recording to monitor emotional states in rats during PPI testing. We altered the predictability of the PPI trials to examine any alterations in gating and emotional regulation. We also examined PPI in animals selectively bred for high or low levels of 50 kHz USV emission. Rats emitted high levels of 22 kHz calls consistently throughout the PPI session. USVs were sensitive to prepulses during the PPI session similar to startle. USV rate was sensitive to predictability among the different levels tested and across repeated experiences. Startle and inhibition of startle were not affected by predictability in a similar manner. No significant differences for PPI or startle were found related the different levels of predictability; however, there was a reduction in USV signals and an enhancement of PPI after repeated exposure. Animals selectively bred to emit high levels of USVs emitted significantly higher levels of USVs during the PPI session and a reduced ASR compared to the low and random selective lines. Overall, the results support the idea that PPI tests in rodents induce high levels of negative affect and that manipulating emotional styles of the animals alters the negative impact of the gating session as well as the intensity of the startle response. PMID:23850353

Pre-movement gating of somatosensory evoked potentials in Segawa disease.

PubMed

Kimura, Kazue; Nagao, Yuri; Hachimori, Kei; Hayashi, Masaharu; Nomura, Yoshiko; Segawa, Masaya

2016-01-01

Segawa disease (SD), an autosomal dominant dopa-responsive dystonia with marked diurnal fluctuation, can be clinically classified into the postural dystonia type (SD-P) and action dystonia type (SD-A). Compared to SD-A, SD-P has an earlier onset and is characterized by postural dystonia. In SD-A, along with postural dystonia, dystonic movements appear in late childhood. To evaluate the differences between these two types of SD, we studied the gating of SEPs, which is useful to investigate sensory-motor integration and might be one of the methods to detect the thalamo-cortical involvement. Fourteen patients with SD (11-63 years) and 18 age-matched normal subjects (11-51 years) were studied. Among the 14 patients with SD, 8 patients had SD-P and 6 had SD-A. Using median nerve stimulation at the wrist, the amplitude of the frontal N30 (FrN30) was compared between pre-movement and rest conditions. We found that the amplitude of the contralateral FrN30 was attenuated before movement in normal controls and in the majority of both SD types. On the other hand, the pre-movement-rest amplitude ratio in patients with SD-A was significantly larger than in patients with SD-P (P=0.0025). No significant differences were observed in the pre-movement-rest ratio between SD-P and normal subjects. The preservation or impairment of pre-movement gating shown here suggests a physiological difference between the two types of SD. More specifically, sensorimotor integration of the basal ganglia-thalamo-cortical circuits may be intact in SD-P, but are affected in SD-A. We discuss the different pathophysiology seen in the different phenotype of SD based on the different developmental involvement in the basal ganglia. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Ultrasonic vocalizations, predictability and sensorimotor gating in the rat.

PubMed

Webber, Emily S; Mankin, David E; McGraw, Justin J; Beckwith, Travis J; Cromwell, Howard C

2013-09-15

Prepulse inhibition (PPI) is a measure of sensorimotor gating in diverse groups of animals including humans. Emotional states can influence PPI in humans both in typical subjects and in individuals with mental illness. Little is known about emotional regulation during PPI in rodents. We used ultrasonic vocalization recording to monitor emotional states in rats during PPI testing. We altered the predictability of the PPI trials to examine any alterations in gating and emotional regulation. We also examined PPI in animals selectively bred for high or low levels of 50kHz USV emission. Rats emitted high levels of 22kHz calls consistently throughout the PPI session. USVs were sensitive to prepulses during the PPI session similar to startle. USV rate was sensitive to predictability among the different levels tested and across repeated experiences. Startle and inhibition of startle were not affected by predictability in a similar manner. No significant differences for PPI or startle were found related to the different levels of predictability; however, there was a reduction in USV signals and an enhancement of PPI after repeated exposure. Animals selectively bred to emit high levels of USVs emitted significantly higher levels of USVs during the PPI session and a reduced ASR compared to the low and random selective lines. Overall, the results support the idea that PPI tests in rodents induce high levels of negative affect and that manipulating emotional styles of the animals alters the negative impact of the gating session as well as the intensity of the startle response. Copyright © 2013 Elsevier B.V. All rights reserved.

Startle habituation, sensory, and sensorimotor gating in trauma-affected refugees with posttraumatic stress disorder.

PubMed

Meteran, Hanieh; Vindbjerg, Erik; Uldall, Sigurd Wiingaard; Glenthøj, Birte; Carlsson, Jessica; Oranje, Bob

2018-05-17

Impairments in mechanisms underlying early information processing have been reported in posttraumatic stress disorder (PTSD); however, findings in the existing literature are inconsistent. This current study capitalizes on technological advancements of research on electroencephalographic event-related potential and applies it to a novel PTSD population consisting of trauma-affected refugees. A total of 25 trauma-affected refugees with PTSD and 20 healthy refugee controls matched on age, gender, and country of origin completed the study. In two distinct auditory paradigms sensory gating, indexed as P50 suppression, and sensorimotor gating, indexed as prepulse inhibition (PPI), startle reactivity, and habituation of the eye-blink startle response were examined. Within the P50 paradigm, N100 and P200 amplitudes were also assessed. In addition, correlations between psychophysiological and clinical measures were investigated. PTSD patients demonstrated significantly elevated stimuli responses across the two paradigms, reflected in both increased amplitude of the eye-blink startle response, and increased N100 and P200 amplitudes relative to healthy refugee controls. We found a trend toward reduced habituation in the patients, while the groups did not differ in PPI and P50 suppression. Among correlations, we found that eye-blink startle responses were associated with higher overall illness severity and lower levels of functioning. Fundamental gating mechanisms appeared intact, while the pattern of deficits in trauma-affected refugees with PTSD point toward a different form of sensory overload, an overall neural hypersensitivity and disrupted the ability to down-regulate stimuli responses. This study represents an initial step toward elucidating sensory processing deficits in a PTSD subgroup.

Prolonged cortical silent period but normal sensorimotor plasticity in spinocerebellar ataxia 6.

PubMed

Teo, James T H; Schneider, Susanne A; Cheeran, Binith J; Fernandez-del-Olmo, Miguel; Giunti, Paola; Rothwell, John C; Bhatia, Kailash P

2008-02-15

Spinocerebellar ataxia 6 (SCA6) is a hereditary disease characterized by a trinucleotide repeat expansion in the CACNA1A gene and late-onset bilateral cerebellar atrophy. It is unclear if there is significant pathology outside of the cerebellum. We used transcranial magnetic stimulation to assess sensorimotor cortical circuits and cortical plasticity in 8 SCA6 patients and 8 age-matched controls. Behavioral performance was assessed using a rhythmic tapping task. Neurophysiological measures of SCA6 patients showed a prolonged cortical silent period (CSP) but normal MEP recruitment curve, short-latency afferent inhibition, long-latency afferent inhibition and ipsilateral silent period. Paired-associative stimulation induction also increased motor-evoked potentials normally. SCA6 patients had greater variability with cued rhythmic tapping than normals and deteriorated when the cue was removed; in comparison, normal subjects had similar variability between cued and uncued rhythmic tapping. Analysis using a Wing-Kristofferson timing model indicated that both clock variance and motor delay variance were abnormal. Conclusion. In SCA6, the circuits for sensorimotor integration and the mechanisms for LTP-like plasticity in the sensorimotor cortex are unimpaired. A prolonged CSP in SCA6 just like in other cerebellar atrophies would suggest that this neurophysiological change typifies cerebellar dysfunction. 2007 Movement Disorder Society

CPB-K mice a mouse model of schizophrenia? Differences in dopaminergic, serotonergic and behavioral markers compared to BALB/cJ mice.

PubMed

Panther, P; Nullmeier, S; Dobrowolny, H; Schwegler, H; Wolf, R

2012-04-21

Schizophrenia is characterized by disturbances in social behavior, sensorimotor gating and cognitive function, that are discussed to be caused by a termination of different transmitter systems. Beside morphological alterations in cortical and subcortical areas reduced AMPA- NMDA-, 5-HT2-receptor densities and increased 5-HT1-receptor densities are found in the hippocampus.The two inbred mouse strains CPB-K and BALB/cJ are known to display considerable differences in cognitive function and prepulse inhibition, a stable marker of sensorimotor gating. Furthermore, CPB-K mice exhibit lower NMDA-, AMPA- and increased 5-HT-receptor densities in the hippocampus as compared to BALB/cJ mice. We investigated both mouse strains in social interaction test for differences in social behavior and with immuncytochemical approaches for alterations of dopaminergic and serotonergic parameters. Our results can be summarized as follows: compared to BALB/cJ, CPB-K mice showed:(1) significantly reduced traveling distance and number of contacts in social interaction test, (2) differences in the number of serotonin transporter-immunoreactive neurons and volume of raphe nuclei and a lower serotonergic fiber density in the ventral and dorsal hippocampal subfields CA1 and CA3, (3) no alterations of dopaminergic markers like neuron number, neuron density and volume in subregions of substantia nigra and ventral tegmental area, but a significantly higher dopaminergic fiber density in the dorsal hippocampus, the ventral hippocampus of CA1 and gyrus dentatus, (4) no significant differences in serotonergic and dopaminergic fiber densities in the amygdala.Based on our results and previous studies, CPB-K mice compared to BALB/cJ may serve as an important model to understand the interaction of the serotonergic and dopaminergic system and their impact on sensorimotor gating and cognitive function as related to neuropsychiatric disorders like schizophrenia. 2012 Elsevier B.V. All rights reserved.

Evaluation of cortical plasticity in children with cerebral palsy undergoing constraint-induced movement therapy based on functional near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Cao, Jianwei; Khan, Bilal; Hervey, Nathan; Tian, Fenghua; Delgado, Mauricio R.; Clegg, Nancy J.; Smith, Linsley; Roberts, Heather; Tulchin-Francis, Kirsten; Shierk, Angela; Shagman, Laura; MacFarlane, Duncan; Liu, Hanli; Alexandrakis, George

2015-04-01

Sensorimotor cortex plasticity induced by constraint-induced movement therapy (CIMT) in six children (10.2±2.1 years old) with hemiplegic cerebral palsy was assessed by functional near-infrared spectroscopy (fNIRS). The activation laterality index and time-to-peak/duration during a finger-tapping task and the resting-state functional connectivity were quantified before, immediately after, and 6 months after CIMT. These fNIRS-based metrics were used to help explain changes in clinical scores of manual performance obtained concurrently with imaging time points. Five age-matched healthy children (9.8±1.3 years old) were also imaged to provide comparative activation metrics for normal controls. Interestingly, the activation time-to-peak/duration for all sensorimotor centers displayed significant normalization immediately after CIMT that persisted 6 months later. In contrast to this improved localized activation response, the laterality index and resting-state connectivity metrics that depended on communication between sensorimotor centers improved immediately after CIMT, but relapsed 6 months later. In addition, for the subjects measured in this work, there was either a trade-off between improving unimanual versus bimanual performance when sensorimotor activation patterns normalized after CIMT, or an improvement occurred in both unimanual and bimanual performance but at the cost of very abnormal plastic changes in sensorimotor activity.

Brief Report: Sensorimotor Gating in Idiopathic Autism and Autism Associated with Fragile X Syndrome

ERIC Educational Resources Information Center

Yuhas, Jennifer; Cordeiro, Lisa; Tassone, Flora; Ballinger, Elizabeth; Schneider, Andrea; Long, James M.; Ornitz, Edward M.; Hessl, David

2011-01-01

Prepulse inhibition (PPI) may useful for exploring the proposed shared neurobiology between idiopathic autism and autism caused by FXS. We compared PPI in four groups: typically developing controls (n = 18), FXS and autism (FXS+A; n = 15), FXS without autism spectrum disorder (FXS-A; n = 17), and idiopathic autism (IA; n = 15). Relative to…

Animal Models of Maladaptive Traits: Disorders in Sensorimotor Gating and Attentional Quantifiable Responses as Possible Endophenotypes

PubMed Central

Vargas, Juan P.; Díaz, Estrella; Portavella, Manuel; López, Juan C.

2016-01-01

Traditional diagnostic scales are based on a number of symptoms to evaluate and classify mental diseases. In many cases, this process becomes subjective, since the patient must calibrate the magnitude of his/her symptoms and therefore the severity of his/her disorder. A completely different approach is based on the study of the more vulnerable traits of cognitive disorders. In this regard, animal models of mental illness could be a useful tool to characterize indicators of possible cognitive dysfunctions in humans. Specifically, several cognitive disorders such as schizophrenia involve a dysfunction in the mesocorticolimbic dopaminergic system during development. These variations in dopamine levels or dopamine receptor sensibility correlate with many behavioral disturbances. These behaviors may be included in a specific phenotype and may be analyzed under controlled conditions in the laboratory. The present study provides an introductory overview of different quantitative traits that could be used as a possible risk indicator for different mental disorders, helping to define a specific endophenotype. Specifically, we examine different experimental procedures to measure impaired response in attention linked to sensorimotor gating as a possible personality trait involved in maladaptive behaviors. PMID:26925020

Behavioural and functional characterization of Kv10.1 (Eag1) knockout mice

PubMed Central

Ufartes, Roser; Schneider, Tomasz; Mortensen, Lena Sünke; de Juan Romero, Camino; Hentrich, Klaus; Knoetgen, Hendrik; Beilinson, Vadim; Moebius, Wiebke; Tarabykin, Victor; Alves, Frauke; Pardo, Luis A.; Rawlins, J. Nicholas P.; Stuehmer, Walter

2013-01-01

Kv10.1 (Eag1), member of the Kv10 family of voltage-gated potassium channels, is preferentially expressed in adult brain. The aim of the present study was to unravel the functional role of Kv10.1 in the brain by generating knockout mice, where the voltage sensor and pore region of Kv10.1 were removed to render non-functional proteins through deletion of exon 7 of the KCNH1 gene using the ‘3 Lox P strategy’. Kv10.1-deficient mice show no obvious alterations during embryogenesis and develop normally to adulthood; cortex, hippocampus and cerebellum appear anatomically normal. Other tests, including general health screen, sensorimotor functioning and gating, anxiety, social behaviour, learning and memory did not show any functional aberrations in Kv10.1 null mice. Kv10.1 null mice display mild hyperactivity and longer-lasting haloperidol-induced catalepsy, but there was no difference between genotypes in amphetamine sensitization and withdrawal, reactivity to apomorphine and haloperidol in the prepulse inhibition tests or to antidepressants in the haloperidol-induced catalepsy. Furthermore, electrical properties of Kv10.1 in cerebellar Purkinje cells did not show any difference between genotypes. Bearing in mind that Kv10.1 is overexpressed in over 70% of all human tumours and that its inhibition leads to a reduced tumour cell proliferation, the fact that deletion of Kv10.1 does not show a marked phenotype is a prerequisite for utilizing Kv10.1 blocking and/or reduction techniques, such as siRNA, to treat cancer. PMID:23424202

The D1CT-7 mouse model of Tourette syndrome displays sensorimotor gating deficits in response to spatial confinement.

PubMed

Godar, Sean C; Mosher, Laura J; Strathman, Hunter J; Gochi, Andrea M; Jones, Cori M; Fowler, Stephen C; Bortolato, Marco

2016-07-01

The D1CT-7 mouse is one of the best known animal models of Tourette syndrome (TS), featuring spontaneous tic-like behaviours sensitive to standard TS therapies; these characteristics ensure a high face and predictive validity of this model, yet its construct validity remains elusive. To address this issue, we studied the responses of D1CT-7 mice to two critical components of TS pathophysiology: the exacerbation of tic-like behaviours in response to stress and the presence of sensorimotor gating deficits, which are thought to reflect the perceptual alterations causing the tics. D1CT-7 and wild-type (WT) littermates were subjected to a 20 min session of spatial confinement (SC) within an inescapable, 10 cm wide cylindrical enclosure. Changes in plasma corticosterone levels, tic-like behaviours and other spontaneous responses were measured. SC-exposed mice were also tested for the prepulse inhibition (PPI) of the startle response (a sensorimotor gating index) and other TS-related behaviours, including open-field locomotion, novel object exploration and social interaction and compared with non-confined counterparts. SC produced a marked increase in corticosterone concentrations in both D1CT-7 and WT mice. In D1CT-7, but not WT mice, SC exacerbated tic-like and digging behaviours, and triggered PPI deficits and aggressive responses. Conversely, SC did not modify locomotor activity or novel object exploration in D1CT-7 mice. Both tic-like behaviours and PPI impairments in SC-exposed D1CT-7 mice were inhibited by standard TS therapies and D1 dopamine receptor antagonism. These findings collectively support the translational and construct validity of D1CT-7 mice with respect to TS. This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc. © 2015 The British Pharmacological Society.

Somatostatin-28 modulates prepulse inhibition of the acoustic startle response, reward processes and spontaneous locomotor activity in rats

PubMed Central

Semenova, Svetlana; Hoyer, Daniel; Geyer, Mark A.; Markou, Athina

2011-01-01

Somatostatins have been shown to be involved in the pathophysiology of motor and affective disorders, as well as psychiatry disorders, including schizophrenia. We hypothesized that in addition to motor function, somatostatin may be involved in somatosensory gating and reward processes that have been shown to be dysregulated in schizophrenia. Accordingly, we evaluated the effects of intracerebroventricular administration of somatostatin-28 on spontaneous locomotor and exploratory behavior measured in a behavioral pattern monitor, sensorimotor gating, prepulse inhibition (PPI) of the acoustic startle reflex, and brain reward function (measured in a discrete trial intracranial self-stimulation procedure) in rats. Somatostatin-28 decreased spontaneous locomotor activity during the first 10 min of a 60 min testing session with no apparent changes in the exploratory activity of rats. The highest somatostatin-28 dose (10 μg/5 μl/side) induced PPI deficits with no effect on the acoustic startle response or startle response habituation. The somatostatin-induced PPI deficit was partially reversed by administration of SRA-880, a selective somatostatin 1 (sst1) receptor antagonist. Somatostatin-28 also induced elevations in brain reward thresholds, reflecting an anhedonic-like state. SRA-880 had no effect on brain reward function under baseline conditions. Altogether these findings suggest that somatostatin-28 modulates PPI and brain reward function but does not have a robust effect on spontaneous exploratory activity. Thus, increases in somatostatin transmission may represent one of the neurochemical mechanisms underlying anhedonia, one of the negative symptoms of schizophrenia, and sensorimotor gating deficits associated with cognitive impairments in schizophrenia patients. PMID:20537385

Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon

PubMed Central

Macrì, Simone; Ceci, Chiara; Onori, Martina Proietti; Invernizzi, Roberto William; Bartolini, Erika; Altabella, Luisa; Canese, Rossella; Imperi, Monica; Orefici, Graziella; Creti, Roberta; Margarit, Immaculada; Magliozzi, Roberta; Laviola, Giovanni

2015-01-01

Repeated exposure to Group-A β-Haemolytic Streptococcus (GAS) may constitute a vulnerability factor in the onset and course of pediatric motor disturbances. GAS infections/colonization can stimulate the production of antibodies, which may cross the blood brain barrier, target selected brain areas (e.g. basal ganglia), and exacerbate motor alterations. Here, we exposed developing SJL male mice to four injections with a GAS homogenate and evaluated the following domains: motor coordination; general locomotion; repetitive behaviors; perseverative responses; and sensorimotor gating (pre-pulse inhibition, PPI). To demonstrate that behavioral changes were associated with immune-mediated brain alterations, we analyzed, in selected brain areas, the presence of infiltrates and microglial activation (immunohistochemistry), monoamines (HPLC), and brain metabolites (in vivo Magnetic Resonance Spectroscopy). GAS-exposed mice showed increased repetitive and perseverative behaviors, impaired PPI, and reduced concentrations of serotonin in prefrontal cortex, a brain area linked to the behavioral domains investigated, wherein they also showed remarkable elevations in lactate. Active inflammatory processes were substantiated by the observation of infiltrates and microglial activation in the white matter of the anterior diencephalon. These data support the hypothesis that repeated GAS exposure may elicit inflammatory responses in brain areas involved in motor control and perseverative behavior, and result in phenotypic abnormalities. PMID:26304458

Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon.

PubMed

Macrì, Simone; Ceci, Chiara; Onori, Martina Proietti; Invernizzi, Roberto William; Bartolini, Erika; Altabella, Luisa; Canese, Rossella; Imperi, Monica; Orefici, Graziella; Creti, Roberta; Margarit, Immaculada; Magliozzi, Roberta; Laviola, Giovanni

2015-08-25

Repeated exposure to Group-A β-Haemolytic Streptococcus (GAS) may constitute a vulnerability factor in the onset and course of pediatric motor disturbances. GAS infections/colonization can stimulate the production of antibodies, which may cross the blood brain barrier, target selected brain areas (e.g. basal ganglia), and exacerbate motor alterations. Here, we exposed developing SJL male mice to four injections with a GAS homogenate and evaluated the following domains: motor coordination; general locomotion; repetitive behaviors; perseverative responses; and sensorimotor gating (pre-pulse inhibition, PPI). To demonstrate that behavioral changes were associated with immune-mediated brain alterations, we analyzed, in selected brain areas, the presence of infiltrates and microglial activation (immunohistochemistry), monoamines (HPLC), and brain metabolites (in vivo Magnetic Resonance Spectroscopy). GAS-exposed mice showed increased repetitive and perseverative behaviors, impaired PPI, and reduced concentrations of serotonin in prefrontal cortex, a brain area linked to the behavioral domains investigated, wherein they also showed remarkable elevations in lactate. Active inflammatory processes were substantiated by the observation of infiltrates and microglial activation in the white matter of the anterior diencephalon. These data support the hypothesis that repeated GAS exposure may elicit inflammatory responses in brain areas involved in motor control and perseverative behavior, and result in phenotypic abnormalities.

Chrna7 deficient mice manifest no consistent neuropsychiatric and behavioral phenotypes.

PubMed

Yin, Jiani; Chen, Wu; Yang, Hongxing; Xue, Mingshan; Schaaf, Christian P

2017-01-03

The alpha7 nicotinic acetylcholine receptor, encoded by the CHRNA7 gene, has been implicated in various psychiatric and behavioral disorders, including schizophrenia, bipolar disorder, epilepsy, autism, Alzheimer's disease, and Parkinson's disease, and is considered a potential target for therapeutic intervention. 15q13.3 microdeletion syndrome is a rare genetic disorder, caused by submicroscopic deletions on chromosome 15q. CHRNA7 is the only gene in this locus that has been deleted entirely in cases involving the smallest microdeletions. Affected individuals manifest variable neurological and behavioral phenotypes, which commonly include developmental delay/intellectual disability, epilepsy, and autism spectrum disorder. Subsets of patients have short attention spans, aggressive behaviors, mood disorders, or schizophrenia. Previous behavioral studies suggested that Chrna7 deficient mice had attention deficits, but were normal in baseline behavioral responses, learning, memory, and sensorimotor gating. Given a growing interest in CHRNA7-related diseases and a better appreciation of its associated human phenotypes, an in-depth behavioral characterization of the Chrna7 deficient mouse model appeared prudent. This study was designed to investigate whether Chrna7 deficient mice manifest phenotypes related to those seen in human individuals, using an array of 12 behavioral assessments and electroencephalogram (EEG) recordings on freely-moving mice. Examined phenotypes included social interaction, compulsive behaviors, aggression, hyperactivity, anxiety, depression, and somatosensory gating. Our data suggests that mouse behavior and EEG recordings are not sensitive to decreased Chrna7 copy number.

Increased sensorimotor network activity in DYT1 dystonia: a functional imaging study

PubMed Central

Argyelan, Miklos; Habeck, Christian; Ghilardi, M. Felice; Fitzpatrick, Toni; Dhawan, Vijay; Pourfar, Michael; Bressman, Susan B.; Eidelberg, David

2010-01-01

Neurophysiological studies have provided evidence of primary motor cortex hyperexcitability in primary dystonia, but several functional imaging studies suggest otherwise. To address this issue, we measured sensorimotor activation at both the regional and network levels in carriers of the DYT1 dystonia mutation and in control subjects. We used 15Oxygen-labelled water and positron emission tomography to scan nine manifesting DYT1 carriers, 10 non-manifesting DYT1 carriers and 12 age-matched controls while they performed a kinematically controlled motor task; they were also scanned in a non-motor audio-visual control condition. Within- and between-group contrasts were analysed with statistical parametric mapping. For network analysis, we first identified a normal motor-related activation pattern in a set of 39 motor and audio-visual scans acquired in an independent cohort of 18 healthy volunteer subjects. The expression of this pattern was prospectively quantified in the motor and control scans acquired in each of the gene carriers and controls. Network values for the three groups were compared with ANOVA and post hoc contrasts. Voxel-wise comparison of DYT1 carriers and controls revealed abnormally increased motor activation responses in the former group (P < 0.05, corrected; statistical parametric mapping), localized to the sensorimotor cortex, dorsal premotor cortex, supplementary motor area and the inferior parietal cortex. Network analysis of the normative derivation cohort revealed a significant normal motor-related activation pattern topography (P < 0.0001) characterized by covarying neural activity in the sensorimotor cortex, dorsal premotor cortex, supplementary motor area and cerebellum. In the study cohort, normal motor-related activation pattern expression measured during movement was abnormally elevated in the manifesting gene carriers (P < 0.001) but not in their non-manifesting counterparts. In contrast, in the non-motor control condition, abnormal increases in network activity were present in both groups of gene carriers (P < 0.001). In this condition, normal motor-related activation pattern expression in non-manifesting carriers was greater than in controls, but lower than in affected carriers. In the latter group, measures of normal motor-related activation pattern expression in the audio-visual condition correlated with independent dystonia clinical ratings (r = 0.70, P = 0.04). These findings confirm that overexcitability of the sensorimotor system is a robust feature of dystonia. The presence of elevated normal motor-related activation pattern expression in the non-motor condition suggests that abnormal integration of audio-visual input with sensorimotor network activity is an important trait feature of this disorder. Lastly, quantification of normal motor-related activation pattern expression in individual cases may have utility as an objective descriptor of therapeutic response in trials of new treatments for dystonia and related disorders. PMID:20207699

Adaptation to Laterally Displacing Prisms in Anisometropic Amblyopia.

PubMed

Sklar, Jaime C; Goltz, Herbert C; Gane, Luke; Wong, Agnes M F

2015-06-01

Using visual feedback to modify sensorimotor output in response to changes in the external environment is essential for daily function. Prism adaptation is a well-established experimental paradigm to quantify sensorimotor adaptation; that is, how the sensorimotor system adapts to an optically-altered visuospatial environment. Amblyopia is a neurodevelopmental disorder characterized by spatiotemporal deficits in vision that impacts manual and oculomotor function. This study explored the effects of anisometropic amblyopia on prism adaptation. Eight participants with anisometropic amblyopia and 11 visually-normal adults, all right-handed, were tested. Participants pointed to visual targets and were presented with feedback of hand position near the terminus of limb movement in three blocks: baseline, adaptation, and deadaptation. Adaptation was induced by viewing with binocular 11.4° (20 prism diopter [PD]) left-shifting prisms. All tasks were performed during binocular viewing. Participants with anisometropic amblyopia required significantly more trials (i.e., increased time constant) to adapt to prismatic optical displacement than visually-normal controls. During the rapid error correction phase of adaptation, people with anisometropic amblyopia also exhibited greater variance in motor output than visually-normal controls. Amblyopia impacts on the ability to adapt the sensorimotor system to an optically-displaced visual environment. The increased time constant and greater variance in motor output during the rapid error correction phase of adaptation may indicate deficits in processing of visual information as a result of degraded spatiotemporal vision in amblyopia.

Normalization of sensorimotor integration by repetitive transcranial magnetic stimulation in cervical dystonia.

PubMed

Zittel, S; Helmich, R C; Demiralay, C; Münchau, A; Bäumer, T

2015-08-01

Previous studies indicated that sensorimotor integration and plasticity of the sensorimotor system are impaired in dystonia patients. We investigated motor evoked potential amplitudes and short latency afferent inhibition to examine corticospinal excitability and cortical sensorimotor integration, before and after inhibitory 1 Hz repetitive transcranial magnetic stimulation over primary sensory and primary motor cortex in patients with cervical dystonia (n = 12). Motor evoked potentials were recorded from the right first dorsal interosseous muscle after application of unconditioned transcranial magnetic test stimuli and after previous conditioning electrical stimulation of the right index finger at short interstimulus intervals of 25, 30 and 40 ms. Results were compared to a group of healthy age-matched controls. At baseline, motor evoked potential amplitudes did not differ between groups. Short latency afferent inhibition was reduced in cervical dystonia patients compared to healthy controls. Inhibitory 1 Hz sensory cortex repetitive transcranial magnetic stimulation but not motor cortex repetitive transcranial magnetic stimulation increased motor evoked potential amplitudes in cervical dystonia patients. Additionally, both 1 Hz repetitive transcranial magnetic stimulation over primary sensory and primary motor cortex normalized short latency afferent inhibition in these patients. In healthy subjects, sensory repetitive transcranial magnetic stimulation had no influence on motor evoked potential amplitudes and short latency afferent inhibition. Plasticity of sensorimotor circuits is altered in cervical dystonia patients.

FNIRS-based evaluation of cortical plasticity in children with cerebral palsy undergoing constraint-induced movement therapy

NASA Astrophysics Data System (ADS)

Cao, Jianwei; Khan, Bilal; Hervey, Nathan; Tian, Fenghua; Delgado, Mauricio R.; Clegg, Nancy J.; Smith, Linsley; Roberts, Heather; Tulchin-Francis, Kirsten; Shierk, Angela; Shagman, Laura; MacFarlane, Duncan; Liu, Hanli; Alexandrakis, George

2015-03-01

Sensorimotor cortex plasticity induced by constraint-induced movement therapy (CIMT) in six children (10.2 ± 2.1 years old) with hemiplegic cerebral palsy (CP) was assessed by functional near-infrared spectroscopy (fNIRS). The activation laterality index and time-to-peak/duration during a finger tapping task were quantified before, immediately after, and six months after CIMT. Five age-matched healthy children (9.8 ± 1.3 years old) were also imaged at the same time points to provide comparative activation metrics for normal controls. In children with CP the activation time-to-peak/duration for all sensorimotor centers displayed significant normalization immediately after CIMT that persisted six months later. In contrast to this longer term improvement in localized activation response, the laterality index that depended on communication between sensorimotor centers improved immediately after CIMT, but relapsed six months later.

Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome

PubMed Central

Xu, Meiyu; Kobets, Andrew; Du, Jung-Chieh; Lennington, Jessica; Li, Lina; Banasr, Mounira; Duman, Ronald S.; Vaccarino, Flora M.; DiLeone, Ralph J.; Pittenger, Christopher

2015-01-01

Gilles de la Tourette syndrome (TS) is characterized by tics, which are transiently worsened by stress, acute administration of dopaminergic drugs, and by subtle deficits in motor coordination and sensorimotor gating. It represents the most severe end of a spectrum of tic disorders that, in aggregate, affect ∼5% of the population. Available treatments are frequently inadequate, and the pathophysiology is poorly understood. Postmortem studies have revealed a reduction in specific striatal interneurons, including the large cholinergic interneurons, in severe disease. We tested the hypothesis that this deficit is sufficient to produce aspects of the phenomenology of TS, using a strategy for targeted, specific cell ablation in mice. We achieved ∼50% ablation of the cholinergic interneurons of the striatum, recapitulating the deficit observed in patients postmortem, without any effect on GABAergic markers or on parvalbumin-expressing fast-spiking interneurons. Interneuron ablation in the dorsolateral striatum (DLS), corresponding roughly to the human putamen, led to tic-like stereotypies after either acute stress or d-amphetamine challenge; ablation in the dorsomedial striatum, in contrast, did not. DLS interneuron ablation also led to a deficit in coordination on the rotorod, but not to any abnormalities in prepulse inhibition, a measure of sensorimotor gating. These results support the causal sufficiency of cholinergic interneuron deficits in the DLS to produce some, but not all, of the characteristic symptoms of TS. PMID:25561540

Ontogeny of sensorimotor gating and short-term memory processing throughout the adolescent period in rats.

PubMed

Goepfrich, Anja A; Friemel, Chris M; Pauen, Sabina; Schneider, Miriam

2017-06-01

Adolescence and puberty are highly susceptible developmental periods during which the neuronal organization and maturation of the brain is completed. The endocannabinoid (eCB) system, which is well known to modulate cognitive processing, undergoes profound and transient developmental changes during adolescence. With the present study we were aiming to examine the ontogeny of cognitive skills throughout adolescence in male rats and clarify the potential modulatory role of CB1 receptor signalling. Cognitive skills were assessed repeatedly every 10th day in rats throughout adolescence. All animals were tested for object recognition memory and prepulse inhibition of the acoustic startle reflex. Although cognitive performance in short-term memory as well as sensorimotor gating abilities were decreased during puberty compared to adulthood, both tasks were found to show different developmental trajectories throughout adolescence. A low dose of the CB1 receptor antagonist/inverse agonist SR141716 was found to improve recognition memory specifically in pubertal animals while not affecting behavioral performance at other ages tested. The present findings demonstrate that the developmental trajectory of cognitive abilities does not occur linearly for all cognitive processes and is strongly influenced by pubertal maturation. Developmental alterations within the eCB system at puberty onset may be involved in these changes in cognitive processing. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Sleep duration, depression, and oxytocinergic genotype influence prepulse inhibition of the startle reflex in postpartum women.

PubMed

Comasco, Erika; Gulinello, Maria; Hellgren, Charlotte; Skalkidou, Alkistis; Sylven, Sara; Sundström-Poromaa, Inger

2016-04-01

The postpartum period is characterized by a post-withdrawal hormonal status, sleep deprivation, and susceptibility to affective disorders. Postpartum mothering involves automatic and attentional processes to screen out new external as well as internal stimuli. The present study investigated sensorimotor gating in relation to sleep duration, depression, as well as catecholaminergic and oxytocinergic genotypes in postpartum women. Prepulse inhibition (PPI) of the startle reflex and startle reactivity were assessed two months postpartum in 141 healthy and 29 depressed women. The catechol-O-methyltransferase (COMT) Val158Met, and oxytocin receptor (OXTR) rs237885 and rs53576 polymorphisms were genotyped, and data on sleep duration were collected. Short sleep duration (less than four hours in the preceding night) and postpartum depression were independently associated with lower PPI. Also, women with postpartum depression had higher startle reactivity in comparison with controls. The OXTR rs237885 genotype was related to PPI in an allele dose-dependent mode, with T/T healthy postpartum women carriers displaying the lowest PPI. Reduced sensorimotor gating was associated with sleep deprivation and depressive symptoms during the postpartum period. Individual neurophysiological vulnerability might be mediated by oxytocinergic genotype which relates to bonding and stress response. These findings implicate the putative relevance of lower PPI of the startle response as an objective physiological correlate of liability to postpartum depression. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Normal sensorimotor plasticity in complex regional pain syndrome with fixed posture of the hand.

PubMed

Morgante, Francesca; Naro, Antonino; Terranova, Carmen; Russo, Margherita; Rizzo, Vincenzo; Risitano, Giovanni; Girlanda, Paolo; Quartarone, Angelo

2017-01-01

Movement disorders associated with complex regional pain syndrome type I have been a subject of controversy over the last 10 years regarding their nature and pathophysiology, with an intense debate about the functional (psychogenic) nature of this disorder. The aim of this study was to test sensorimotor plasticity and cortical excitability in patients with complex regional pain syndrome type I who developed a fixed posture of the hand. Ten patients with complex regional pain syndrome type I in the right upper limb and a fixed posture of the hand (disease duration less than 24 months) and 10 age-matched healthy subjects were enrolled. The following parameters of corticospinal excitability were recorded from the abductor pollicis brevis muscle of both hands by transcranial magnetic stimulation: resting and active motor thresholds, short-interval intracortical inhibition and facilitation, cortical silent period, and short- and long-latency afferent inhibition. Sensorimotor plasticity was tested using the paired associative stimulation protocol. Short-interval intracortical inhibition and long-latency afferent inhibition were reduced only in the affected right hand of patients compared with control subjects. Sensorimotor plasticity was comparable to normal subjects, with a preserved topographic specificity. Our data support the view that motor disorder in complex regional pain syndrome type I is not associated with abnormal sensorimotor plasticity, and it shares pathophysiological abnormalities with functional (psychogenic) dystonia rather than with idiopathic dystonia. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Docosahexaenoic acid augments hypothermic neuroprotection in a neonatal rat asphyxia model.

PubMed

Berman, Deborah R; Mozurkewich, Ellen; Liu, Yiqing; Shangguan, Yu; Barks, John D; Silverstein, Faye S

2013-01-01

In neonatal rats, early post-hypoxia-ischemia (HI) administration of the omega-3 fatty acid docosahexaenoic acid (DHA) improves sensorimotor function, but does not attenuate brain damage. To determine if DHA administration in addition to hypothermia, now standard care for neonatal asphyxial brain injury, attenuates post-HI damage and sensorimotor deficits. Seven-day-old (P7) rats underwent right carotid ligation followed by 90 min of 8% O2 exposure. Fifteen minutes later, pups received injections of DHA 2.5 mg/kg (complexed to 25% albumin) or equal volumes of albumin. After a 1-hour recovery, pups were cooled (3 h, 30°C). Sensorimotor and pathology outcomes were initially evaluated on P14. In subsequent experiments, sensorimotor function was evaluated on P14, P21, and P28; histopathology was assessed on P28. At P14, left forepaw function scores (normal: 20/20) were near normal in DHA + hypothermia-treated animals (mean ± SD 19.7 ± 0.7 DHA + hypothermia vs. 12.7 ± 3.5 albumin + hypothermia, p < 0.0001) and brain damage was reduced (mean ± SD right hemisphere damage 38 ± 17% with DHA + hypothermia vs. 56 ± 15% with albumin + hypothermia, p = 0.003). Substantial improvements on three sensorimotor function measures and reduced brain damage were evident up to P28. Unlike post-HI treatment with DHA alone, treatment with DHA + hypothermia produced both sustained functional improvement and reduced brain damage after neonatal HI. Copyright © 2013 S. Karger AG, Basel.

Another Way To View Child Development: An Interactive Approach to the Integration of the Sensorimotor System, Communication and Temperament. Project Ta-kos.

ERIC Educational Resources Information Center

Yoches, Betty; Luera, Margarita

The purpose of this training manual is to assist parents and professionals in understanding how a child's temperament, sensorimotor system, and communication system support each other in helping the child develop a solid foundation for normal growth and development. Training is based on the premise that awareness of the interaction and integration…

Swertisin ameliorates pre-pulse inhibition deficits and cognitive impairment induced by MK-801 in mice.

PubMed

Oh, Hee Kyong; Jeon, Se Jin; Lee, Sunhee; Lee, Hyung Eun; Kim, Eunji; Park, Se Jin; Kim, Ha Neul; Jung, Won Yong; Cheong, Jae Hoon; Jang, Dae Sik; Ryu, Jong Hoon

2017-02-01

Swertisin, a plant-derived C-glucosylflavone, is known to have antidiabetic, anti-inflammatory and antioxidant effects. In the present study, we investigated in mice the effects of swertisin on glutamatergic dysfunction induced by dizocilpine (MK-801), a non-competitive N-methyl-D-aspartate receptor antagonist. In the Acoustic Startle Response test, their MK-801-induced (given 0.2 mg/kg i.p.) pre-pulse inhibition deficit was significantly attenuated by the administration of swertisin (30 mg/kg p.o.). In the Novel Object Recognition Test, the recognition memory impairments that were induced by MK-801 (0.2 mg/kg, given i.p.) were also reversed by administration of swertisin (30 mg/kg p.o.). In addition, swertisin normalized the MK-801-induced elevation of phosphorylation levels of Akt and GSK-3β signaling molecules in the prefrontal cortex. These results indicated that swertisin may be useful in managing the symptoms of schizophrenia, including sensorimotor gating disruption and cognitive impairment, and that these behavioral outcomes may be related to Akt-GSK-3β signaling in the prefrontal cortex.

Assessment of sensorimotor control in adults with surgical correction for idiopathic scoliosis.

PubMed

Pialasse, Jean-Philippe; Mercier, Pierre; Descarreaux, Martin; Simoneau, Martin

2016-10-01

This study aims at verifying if impaired sensorimotor control observed in adolescents and young adults with scoliosis is also present in adult patients who underwent surgery to reduce their spine deformation. The study included ten healthy adults and ten adults with idiopathic scoliosis who underwent surgery to reduce their spine deformation. Galvanic vestibular stimulation was delivered to assess sensorimotor control. Vertical forces under each foot and horizontal displacement of the upper body were measured before, during and after stimulation. Balance control was assessed by calculating the root mean square values of kinematic and kinetic variables. The amplitude of the vestibular-evoked postural response was 3.4 % (0.8-6.0 %) and 4.5 % (-0.4 to 9.5 %) of the maximal range of motion. Therefore, spine surgery did not limit the postural response. Patients with idiopathic scoliosis exhibited larger body sway than the healthy controls during and immediately after vestibular stimulation. The maximal normalized lateral displacement of the body was 0.85 and 0.40 cm/m and maximal normalized vertical force was 0.78 vs. 0.39 N/kg, for idiopathic scoliosis and healthy groups, respectively. This result suggests that dysfunctional sensorimotor integration is still present even in adult idiopathic scoliosis that underwent spine deformation correction.

Interference and Shaping in Sensorimotor Adaptations with Rewards

PubMed Central

Darshan, Ran; Leblois, Arthur; Hansel, David

2014-01-01

When a perturbation is applied in a sensorimotor transformation task, subjects can adapt and maintain performance by either relying on sensory feedback, or, in the absence of such feedback, on information provided by rewards. For example, in a classical rotation task where movement endpoints must be rotated to reach a fixed target, human subjects can successfully adapt their reaching movements solely on the basis of binary rewards, although this proves much more difficult than with visual feedback. Here, we investigate such a reward-driven sensorimotor adaptation process in a minimal computational model of the task. The key assumption of the model is that synaptic plasticity is gated by the reward. We study how the learning dynamics depend on the target size, the movement variability, the rotation angle and the number of targets. We show that when the movement is perturbed for multiple targets, the adaptation process for the different targets can interfere destructively or constructively depending on the similarities between the sensory stimuli (the targets) and the overlap in their neuronal representations. Destructive interferences can result in a drastic slowdown of the adaptation. As a result of interference, the time to adapt varies non-linearly with the number of targets. Our analysis shows that these interferences are weaker if the reward varies smoothly with the subject's performance instead of being binary. We demonstrate how shaping the reward or shaping the task can accelerate the adaptation dramatically by reducing the destructive interferences. We argue that experimentally investigating the dynamics of reward-driven sensorimotor adaptation for more than one sensory stimulus can shed light on the underlying learning rules. PMID:24415925

Male rats with the testicular feminization mutation of the androgen receptor display elevated anxiety-related behavior and corticosterone response to mild stress

PubMed Central

Zuloaga, Damian G.; Poort, Jessica E.; Jordan, Cynthia L.; Breedlove, S. Marc

2011-01-01

Testosterone influences the hypothalamic-pituitary-adrenal axis, anxiety-related behavior, and sensorimotor gating in rodents, but little is known about the role of the androgen receptor (AR) in mediating these influences. We compared levels of the stress hormone corticosterone at baseline and following exposure to a novel object in an open field in wild type (wt) male and female rats, and male rats with the testicular feminization mutation (Tfm) of the AR, which disables its function. Basal corticosterone was equivalent in all groups, but exposure to a novel object in an open field elicited a greater increase in corticosterone in Tfm males and wt females than in wt males. Tfm males also showed increased behavioral indices of anxiety compared to wt males and females in the test. Analysis of the immediate early gene c-Fos expression after exposure to a novel object revealed greater activation in Tfm males than wt males in some regions (medial preoptic area) and lesser activation in others (dentate gyrus, posterodorsal medial amygdala). No differences were found in a measure of sensorimotor gating (prepulse inhibition of the acoustic startle response), although Tfm males had an increased acoustic startle response compared to wt males and females. These findings demonstrate that ARs play a role in regulating anxiety-related behaviors, as well as corticosterone responses and neural activation following exposure to a mild stressor in rats. PMID:21801726

OCD is associated with an altered association between sensorimotor gating and cortical and subcortical 5-HT1b receptor binding

PubMed Central

Pittenger, Christopher; Adams, Thomas. G.; Gallezot, Jean-Dominique; Crowley, Michael J.; Nabulsi, Nabeel; Ropchan, James; Gao, Hong; Kichuk, Stephen A.; Simpson, Ryan; Billingslea, Eileen; Hannestad, Jonas; Bloch, Michael; Mayes, Linda; Bhagwagar, Zubin; Carson, Richard E.

2016-01-01

Obsessive-compulsive disorder (OCD) is characterized by impaired sensorimotor gating, as measured using prepulse inhibition (PPI). This effect may be related to abnormalities in the serotonin (5-HT) system. 5-HT1B agonists can impair PPI, produce OCD-like behaviors in animals, and exacerbate OCD symptoms in humans. We measured 5-HT1B receptor availability using 11C-P943 positron emission tomography (PET) in unmedicated, non-depressed OCD patients (n = 12) and matched healthy controls (HC; n = 12). Usable PPI data were obtained from 20 of these subjects (10 from each group). There were no significant main effects of OCD diagnosis on 5-HT1B receptor availability (11C-P943 BPND); however, the relationship between PPI and 11C-P943 BPND differed dramatically and significantly between groups. 5-HT1B receptor availability in the basal ganglia and thalamus correlated positively with PPI in controls; these correlations were lost or even reversed in the OCD group. In cortical regions there were no significant correlations with PPI in controls, but widespread positive correlations in OCD patients. Positive correlations between 5-HT1B receptor availability and PPI were consistent across diagnostic groups only in two structures, the orbitofrontal cortex and the amygdala. Differential associations of 5-HT1B receptor availability with PPI in patients suggest functionally important alterations in the serotonergic regulation of cortical/subcortical balance in OCD. PMID:26919057

Discharge ratings for tainter gates and roller gates at Lock and Dam No. 7 on the Mississippi River, La Crescent, Minnesota

USGS Publications Warehouse

Corsi, Steven R.; Schuler, J.G.

1995-01-01

Coefficients of discharge (Cgs) ranged fron 0.126 (hg = 1 foot) to 1.089 (hg = 10 feet) for tainter gates and from 0.050 (hg = 1 foot) to 0.302 (hg = 14 feet) for roller gates. Disch^ge was measured at three different tainter gates with the gates closed (hg = 0) to evaluate tH tainter-gate leakage-discharge relations. No measurable leakage was observed. The resulting equations can be used to compute discharge at Lock and Dam No. 7 for the tainter and re Her gates under normal flow conditions. Discharge rating tables for the tainter and roller gates are given with a headwater elevation of 639.00 feet normal pool elevation for selected tailwate" elevations and gate openings.

Behavioral State Modulates the Activity of Brainstem Sensorimotor Neurons

PubMed Central

McArthur, Kimberly L.

2011-01-01

Sensorimotor processing must be modulated according to the animal's behavioral state. A previous study demonstrated that motion responses were strongly state dependent in birds. Vestibular eye and head responses were significantly larger and more compensatory during simulated flight, and a flight-specific vestibular tail response was also characterized. In the current study, we investigated the neural substrates for these state-dependent vestibular behaviors by recording extracellularly from neurons in the vestibular nuclear complex and comparing their spontaneous activity and sensory responses during default and simulated flight states. We show that motion-sensitive neurons in the lateral vestibular nucleus are state dependent. Some neurons increased their spontaneous firing rates during flight, though their increased excitability was not reflected in higher sensory gains. However, other neurons exhibited state-dependent gating of sensory inputs, responding to rotational stimuli only during flight. These results demonstrate that vestibular processing in the brainstem is state dependent and lay the foundation for future studies to investigate the synaptic mechanisms responsible for these modifications. PMID:22090497

Inhibition of 5a-reductase in the nucleus accumbens counters sensorimotor gating deficits induced by dopaminergic activation

PubMed Central

Devoto, Paola; Frau, Roberto; Bini, Valentina; Pillolla, Giuliano; Saba, Pierluigi; Flore, Giovanna; Corona, Marta; Marrosu, Francesco; Bortolato, Marco

2012-01-01

Summary Cogent evidence highlights a key role of neurosteroids and androgens in schizophrenia. We recently reported that inhibition of steroid 5α-reductase (5αR), the rate-limiting enzyme in neurosteroid synthesis and androgen metabolism, elicits antipsychotic-like effects in humans and animal models, without inducing extrapyramidal side effects. To elucidate the anatomical substrates mediating these effects, we investigated the contribution of peripheral and neural structures to the behavioral effects of the 5αR inhibitor finasteride (FIN) on the prepulse inhibition (PPI) of the acoustic startle reflex (ASR), a rat paradigm that dependably simulates the sensorimotor gating impairments observed in schizophrenia and other neuropsychiatric disorders. The potential effect of drug-induced ASR modifications on PPI was excluded by measuring this index both as percent (%PPI) and absolute values (ΔPPI). In both orchidectomized and sham-operated rats, FIN prevented the %PPI deficits induced by the dopamine (DA) receptor agonists apomorphine (APO, 0.25 mg/kg, SC) and d-amphetamine (AMPH, 2.5 mg/kg, SC), although the latter effect was not corroborated by ΔPPI analysis. Conversely, APO-induced PPI deficits were countered by FIN infusions in the brain ventricles (10 μg/1 μl) and in the nucleus accumbens (NAc) shell and core (0.5 μg/0.5 μl/side). No significant PPI-ameliorating effect was observed following FIN injections in other brain regions, including dorsal caudate, basolateral amygdala, ventral hippocampus and medial prefrontal cortex, although a statistical trend was observed for the latter region. The efflux of DA in NAc was increased by systemic, but not intracerebral FIN administration. Taken together, these findings suggest that the role of 5αR in gating regulation is based on post-synaptic mechanisms in the NAc, and is not directly related to alterations in DA efflux in this region. PMID:22029952

Electronical Stimulation of the Midbrain to Promote Recovery from Traumatic Forebrain Injury

DTIC Science & Technology

2010-05-01

learning in a water maze test and normalized sensorimotor performance (movements in a transparent cylinder ). Higher rates of stimulation (20 Hz) or...descending from the nucleus raphe magnus of the medulla could enhance anatomical and behavioral recovery from spinal cord injury in rats if started within...days 4 and 5) and in the cylinder sensorimotor test has been completed for groups A-D. f-h) Months 5-7. “Begin repeat behavioral testing in group

Sensorimotor Control of Tracking Movements at Various Speeds for Stroke Patients as Well as Age-Matched and Young Healthy Subjects

PubMed Central

Ao, Di; Song, Rong; Tong, Kai-yu

2015-01-01

There are aging- and stroke-induced changes on sensorimotor control in daily activities, but their mechanisms have not been well investigated. This study explored speed-, aging-, and stroke-induced changes on sensorimotor control. Eleven stroke patients (affected sides and unaffected sides) and 20 control subjects (10 young and 10 age-matched individuals) were enrolled to perform elbow tracking tasks using sinusoidal trajectories, which included 6 target speeds (15.7, 31.4, 47.1, 62.8, 78.5, and 94.2 deg/s). The actual elbow angle was recorded and displayed on a screen as visual feedback, and three indicators, the root mean square error (RMSE), normalized integrated jerk (NIJ) and integral of the power spectrum density of normalized speed (IPNS), were used to investigate the strategy of sensorimotor control. Both NIJ and IPNS had significant differences among the four groups (P<0.01), and the values were ranked in the following order: young controls < age-matched controls

The Functional Networks of Prepulse Inhibition: Neuronal Connectivity Analysis Based on FDG-PET in Awake and Unrestrained Rats.

PubMed

Rohleder, Cathrin; Wiedermann, Dirk; Neumaier, Bernd; Drzezga, Alexander; Timmermann, Lars; Graf, Rudolf; Leweke, F Markus; Endepols, Heike

2016-01-01

Prepulse inhibition (PPI) is a neuropsychological process during which a weak sensory stimulus ("prepulse") attenuates the motor response ("startle reaction") to a subsequent strong startling stimulus. It is measured as a surrogate marker of sensorimotor gating in patients suffering from neuropsychological diseases such as schizophrenia, as well as in corresponding animal models. A variety of studies has shown that PPI of the acoustical startle reaction comprises three brain circuitries for: (i) startle mediation, (ii) PPI mediation, and (iii) modulation of PPI mediation. While anatomical connections and information flow in the startle and PPI mediation pathways are well known, spatial and temporal interactions of the numerous regions involved in PPI modulation are incompletely understood. We therefore combined [(18)F]fluoro-2-deoxyglucose positron-emission-tomography (FDG-PET) with PPI and resting state control paradigms in awake rats. A battery of subtractive, correlative as well as seed-based functional connectivity analyses revealed a default mode-like network (DMN) active during resting state only. Furthermore, two functional networks were observed during PPI: Metabolic activity in the lateral circuitry was positively correlated with PPI effectiveness and involved the auditory system and emotional regions. The medial network was negatively correlated with PPI effectiveness, i.e., associated with startle, and recruited a spatial/cognitive network. Our study provides evidence for two distinct neuronal networks, whose continuous interplay determines PPI effectiveness in rats, probably by either protecting the prepulse or facilitating startle processing. Discovering similar networks affected in neuropsychological disorders may help to better understand mechanisms of sensorimotor gating deficits and provide new perspectives for therapeutic strategies.

Environmental enrichment reduces innate anxiety with no effect on depression-like behaviour in mice lacking the serotonin transporter.

PubMed

Rogers, Jake; Li, Shanshan; Lanfumey, Laurence; Hannan, Anthony J; Renoir, Thibault

2017-08-14

Along with being the main target of many antidepressant medications, the serotonin transporter (5-HTT) is known to be involved in the pathophysiology of depression and anxiety disorders. In line with this, mice with varying 5-HTT genotypes are invaluable tools to study depression- and anxiety-like behaviours as well as the mechanisms mediating potential therapeutics. There is clear evidence that both genetic and environmental factors play a role in the aetiology of psychiatric disorders. In that regard, housing paradigms which seek to enhance cognitive stimulation and physical activity have been shown to exert beneficial effects in animal models of neuropsychiatric disorders. In the present study, we examined the effects of environmental enrichment on affective-like behaviours and sensorimotor gating function of 5-HTT knock-out (KO) mice. Using the elevated-plus maze and the light-dark box, we found that environmental enrichment ameliorated the abnormal innate anxiety of 5-HTT KO mice on both tests. In contrast, environmental enrichment did not rescue the depression-like behaviour displayed by 5-HTT KO mice in the forced-swim test. Finally, measuring pre-pulse inhibition, we found no effect of genotype or treatment on sensorimotor gating. In conclusion, our data suggest that environmental enrichment specifically reduces innate anxiety of 5-HTT KO mice with no amelioration of the depression-like behaviour. This has implications for the current use of clinical interventions for patients with symptoms of both anxiety and depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Iron Deficiency with or without Anemia Impairs Prepulse Inhibition of the Startle Reflex

PubMed Central

Pisansky, Marc T.; Wickham, Robert J.; Su, Jianjun; Fretham, Stephanie; Yuan, Li-Lian; Sun, Mu; Gewirtz, Jonathan C.; Georgieff, Michael K.

2013-01-01

Iron deficiency (ID) during early life causes long-lasting detrimental cognitive sequelae, many of which are linked to alterations in hippocampus function, dopamine synthesis, and the modulation of dopaminergic circuitry by the hippocampus. These same features have been implicated in the origins of schizophrenia, a neuropsychiatric disorder with significant cognitive impairments. Deficits in sensorimotor gating represent a reliable endophenotype of schizophrenia that can be measured by prepulse inhibition (PPI) of the acoustic startle reflex. Using two rodent model systems, we investigated the influence of early-life ID on PPI in adulthood. To isolate the role of hippocampal iron in PPI, our mouse model utilized a timed (embryonic day 18.5), hippocampus-specific knockout of Slc11a2, a gene coding an important regulator of cellular iron uptake, the divalent metal transport type 1 protein (DMT-1). Our second model used a classic rat dietary-based global ID during gestation, a condition that closely mimics human gestational ID anemia (IDA). Both models exhibited impaired PPI in adulthood. Furthermore, our DMT-1 knockout model displayed reduced long-term potentiation (LTP) and elevated paired pulse facilitation (PPF), electrophysiological results consistent with previous findings in the IDA rat model. These results, in combination with previous findings demonstrating impaired hippocampus functioning and altered dopaminergic and glutamatergic neurotransmission, suggest that iron availability within the hippocampus is critical for the neurodevelopmental processes underlying sensorimotor gating. Ultimately, evidence of reduced PPI in both of our models may offer insights into the roles of fetal ID and the hippocampus in the pathophysiology of schizophrenia. PMID:23733517

Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain.

PubMed

Levin, Raquel; Peres, Fernanda F; Almeida, Valéria; Calzavara, Mariana B; Zuardi, Antonio W; Hallak, Jaime E C; Crippa, José Alexandre S; Abílio, Vanessa C

2014-01-01

Clinical and neurobiological findings suggest that the cannabinoids and the endocannabinoid system may be implicated in the pathophysiology and treatment of schizophrenia. We described that the spontaneously hypertensive rats (SHR) strain presents a schizophrenia behavioral phenotype that is specifically attenuated by antipsychotic drugs, and potentiated by proschizophrenia manipulations. Based on these findings, we have suggested this strain as an animal model of schizophrenia. The aim of this study was to evaluate the effects of cannabinoid drugs on the deficit of prepulse inhibition (PPI) of startle, the main paradigm used to study sensorimotor gating impairment related to schizophrenia, presented by the SHR strain. The following drugs were used: (1) WIN55212,2 (cannabinoid agonist), (2) rimonabant (CB1 antagonist), (3) AM404 (anandamide uptake inhibitor), and (4) cannabidiol (CBD; indirect CB1/CB2 receptor antagonist, among other effects). Wistar rats (WRs) and SHRs were treated with vehicle (VEH) or different doses of WIN55212 (0.3, 1, or 3 mg/kg), rimonabant (0.75, 1.5, or 3 mg/kg), AM404 (1, 5, or 10 mg/kg), or CBD (15, 30, or 60 mg/kg). VEH-treated SHRs showed a decreased PPI when compared to WRs. This PPI deficit was reversed by 1 mg/kg WIN and 30 mg/kg CBD. Conversely, 0.75 mg/kg rimonabant decreased PPI in SHR strain, whereas AM404 did not modify it. Our results reinforce the role of the endocannabinoid system in the sensorimotor gating impairment related to schizophrenia, and point to cannabinoid drugs as potential therapeutic strategies.

Sensorimotor Learning in a Computerized Athletic Training Battery.

PubMed

Krasich, Kristina; Ramger, Ben; Holton, Laura; Wang, Lingling; Mitroff, Stephen R; Gregory Appelbaum, L

2016-01-01

Sensorimotor abilities are crucial for performance in athletic, military, and other occupational activities, and there is great interest in understanding learning in these skills. Here, behavioral performance was measured over three days as twenty-seven participants practiced multiple sessions on the Nike SPARQ Sensory Station (Nike, Inc., Beaverton, Oregon), a computerized visual and motor assessment battery. Wrist-worn actigraphy was recorded to monitor sleep-wake cycles. Significant learning was observed in tasks with high visuomotor control demands but not in tasks of visual sensitivity. Learning was primarily linear, with up to 60% improvement, but did not relate to sleep quality in this normal-sleeping population. These results demonstrate differences in the rate and capacity for learning across perceptual and motor domains, indicating potential targets for sensorimotor training interventions.

Effect of respiratory and cardiac gating on the major diffusion-imaging metrics

PubMed Central

Hamaguchi, Hiroyuki; Sugimori, Hiroyuki; Nakanishi, Mitsuhiro; Nakagawa, Shin; Fujiwara, Taro; Yoshida, Hirokazu; Takamori, Sayaka; Shirato, Hiroki

2016-01-01

The effect of respiratory gating on the major diffusion-imaging metrics and that of cardiac gating on mean kurtosis (MK) are not known. For evaluation of whether the major diffusion-imaging metrics—MK, fractional anisotropy (FA), and mean diffusivity (MD) of the brain—varied between gated and non-gated acquisitions, respiratory-gated, cardiac-gated, and non-gated diffusion-imaging of the brain were performed in 10 healthy volunteers. MK, FA, and MD maps were constructed for all acquisitions, and the histograms were constructed. The normalized peak height and location of the histograms were compared among the acquisitions by use of Friedman and post hoc Wilcoxon tests. The effect of the repetition time (TR) on the diffusion-imaging metrics was also tested, and we corrected for its variation among acquisitions, if necessary. The results showed a shift in the peak location of the MK and MD histograms to the right with an increase in TR (p ≤ 0.01). The corrected peak location of the MK histograms, the normalized peak height of the FA histograms, the normalized peak height and the corrected peak location of the MD histograms varied significantly between the gated and non-gated acquisitions (p < 0.05). These results imply an influence of respiration and cardiac pulsation on the major diffusion-imaging metrics. The gating conditions must be kept identical if reproducible results are to be achieved. PMID:27073115

HMB attenuates muscle loss during sustained energy deficit induced by calorie restriction and endurance exercise.

PubMed

Park, Bong-Sup; Henning, Paul C; Grant, Samuel C; Lee, Won Jun; Lee, Sang-Rok; Arjmandi, Bahram H; Kim, Jeong-Su

2013-12-01

To investigate the efficacy and underlying mechanisms of β-hydroxy-β-methylbutyrate (HMB) on body composition, muscle mass and physical performance under catabolic versus normal training conditions. Mice were divided into four groups (n=10/group): (1) ALT=ad libitum+trained (1 h/d for 3 d/wk); (2) ALTH=ALT+HMB (0.5 g/kg BW/d); (3) C=calorie restricted (-30%)+trained (6 h/d, 6 d/wk); and (4) CH=C+HMB. Repeated in vivo assessments included body composition, grip strength and sensorimotor coordination before and after the experimental protocol, while in vitro analyses included muscle wet weights, expression of selected genes and proteins regulating muscle mass, and myofiber cross-sectional area. ANOVAs were used with significance set at p<0.05. ALTH had greater lean mass than ALT and sensorimotor function increased in ALTH, but decreased in ALT under normal training conditions. Grip strength decreased only in C, but was maintained in CH. Gastrocnemius mass and myofiber CSA were greater in CH than C following catabolic conditions. Gastrocnemius atrogin-1 mRNA expression was elevated in C but not in CH compared to all other groups whereas atrogin-1 protein levels showed no significant changes. HMB improves body composition and sensorimotor function during normal training and attenuates muscle mass and strength loss during catabolic conditions. © 2013.

Effect of long-term stress on H3Ser10 histone phosphorylation in neuronal nuclei of the sensorimotor cortex and midbrain reticular formation in rats with different nervous system excitability.

PubMed

Pavlova, M B; Dyuzhikova, N A; Shiryaeva, N V; Savenko, Yu N; Vaido, A I

2013-07-01

The effects of long-term mental and pain stress on H3Ser10 histone phosphorylation in neurons of the the sensorimotor corex and midbrain reticular formation were studied 24 h, 2 weeks, and 2 months after exposure of rats differing by the nervous system excitability. Rats with high excitability threshold exhibited higher basal level of H3Ser10 histone phosphorylation in the midbrain reticular formation neurons than rats with low excitability threshold. The sensorimotor cortical neurons of the two strains did not differ by this parameter. Stress led to a significant increase in the counts of immunopositive neuronal nuclei in rats with low excitability threshold: the parameter increased significantly in the sensorimotor cortex 24 h after exposure and normalized in 2 weeks after neurotization. In the midbrain reticular formation of this rat strain stress stimulated H3Ser10 histone phosphorylation after 24 h and after 2 weeks; the parameter normalized after neurotization in 2 months. Hence, genetically determined level of the nervous system excitability was essential for the basal level of neuron phosphorylation and for the time course of this process after long-term exposure to mental and pain stress, depending on the brain structure. A probable relationship between H3Ser10 histone phosphorylation process and liability to obsessive compulsive mental disorders in humans was discussed.

Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function.

PubMed

Piwecka, Monika; Glažar, Petar; Hernandez-Miranda, Luis R; Memczak, Sebastian; Wolf, Susanne A; Rybak-Wolf, Agnieszka; Filipchyk, Andrei; Klironomos, Filippos; Cerda Jara, Cledi Alicia; Fenske, Pascal; Trimbuch, Thorsten; Zywitza, Vera; Plass, Mireya; Schreyer, Luisa; Ayoub, Salah; Kocks, Christine; Kühn, Ralf; Rosenmund, Christian; Birchmeier, Carmen; Rajewsky, Nikolaus

2017-09-22

Hundreds of circular RNAs (circRNAs) are highly abundant in the mammalian brain, often with conserved expression. Here we show that the circRNA Cdr1as is massively bound by the microRNAs (miRNAs) miR-7 and miR-671 in human and mouse brains. When the Cdr1as locus was removed from the mouse genome, knockout animals displayed impaired sensorimotor gating-a deficit in the ability to filter out unnecessary information-which is associated with neuropsychiatric disorders. Electrophysiological recordings revealed dysfunctional synaptic transmission. Expression of miR-7 and miR-671 was specifically and posttranscriptionally misregulated in all brain regions analyzed. Expression of immediate early genes such as Fos , a direct miR-7 target, was enhanced in Cdr1as -deficient brains, providing a possible molecular link to the behavioral phenotype. Our data indicate an in vivo loss-of-function circRNA phenotype and suggest that interactions between Cdr1as and miRNAs are important for normal brain function. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

NOTE: A feasibility study of markerless fluoroscopic gating for lung cancer radiotherapy using 4DCT templates

NASA Astrophysics Data System (ADS)

Li, Ruijiang; Lewis, John H.; Cerviño, Laura I.; Jiang, Steve B.

2009-10-01

A major difficulty in conformal lung cancer radiotherapy is respiratory organ motion, which may cause clinically significant targeting errors. Respiratory-gated radiotherapy allows for more precise delivery of prescribed radiation dose to the tumor, while minimizing normal tissue complications. Gating based on external surrogates is limited by its lack of accuracy, while gating based on implanted fiducial markers is limited primarily by the risk of pneumothorax due to marker implantation. Techniques for fluoroscopic gating without implanted fiducial markers (markerless gating) have been developed. These techniques usually require a training fluoroscopic image dataset with marked tumor positions in the images, which limits their clinical implementation. To remove this requirement, this study presents a markerless fluoroscopic gating algorithm based on 4DCT templates. To generate gating signals, we explored the application of three similarity measures or scores between fluoroscopic images and the reference 4DCT template: un-normalized cross-correlation (CC), normalized cross-correlation (NCC) and normalized mutual information (NMI), as well as average intensity (AI) of the region of interest (ROI) in the fluoroscopic images. Performance was evaluated using fluoroscopic and 4DCT data from three lung cancer patients. On average, gating based on CC achieves the highest treatment accuracy given the same efficiency, with a high target coverage (average between 91.9% and 98.6%) for a wide range of nominal duty cycles (20-50%). AI works well for two patients out of three, but failed for the third patient due to interference from the heart. Gating based on NCC and NMI usually failed below 50% nominal duty cycle. Based on this preliminary study with three patients, we found that the proposed CC-based gating algorithm can generate accurate and robust gating signals when using 4DCT reference template. However, this observation is based on results obtained from a very limited dataset, and further investigation on a larger patient population has to be done before its clinical implementation.

Time-frequency analysis of the EEG mu rhythm as a measure of sensorimotor integration in the later stages of swallowing.

PubMed

Cuellar, M; Harkrider, A W; Jenson, D; Thornton, D; Bowers, A; Saltuklaroglu, T

2016-07-01

Electroencephalography (EEG) was used to map the temporal dynamics of sensorimotor integration relative to the strength and timing of muscular activity during swallowing. 64-channel EEG data and surface electromyographic (sEMG) data were recorded from 25 neurologically-healthy adults during swallowing and tongue-tapping. Events were demarcated so that sensorimotor activity primarily from the pharyngeal and esophageal phases of swallowing could be compared to activity resulting from tongue tapping. Independent component analysis identified bilateral clusters of sensorimotor mu components localized to the premotor and primary motor cortices as well as an infrahyoid myogenic cluster. Subsequent event-related spectral perturbations (ERSP) analyses showed event-related desynchronization (ERD) in the spectral power in the alpha (8-13Hz) and beta (15-25Hz) frequency bands of the mu clusters in both tasks. Mu ERD was stronger during swallowing when compared to tongue tapping (pFDR<.05) and the differences in sensorimotor processing between conditions was greater in the right hemisphere than the left, suggesting stronger right hemisphere lateralization for swallowing than tongue-tapping. Mu activity was interpreted as representing a normal feed forward and feedback driven sensorimotor loop during the later stages of swallowing. Results support further use of this novel neuroimaging technique to concurrently map neural and muscle activity during swallowing in clinical populations using EEG. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Influence of Aripiprazole, Risperidone, and Amisulpride on Sensory and Sensorimotor Gating in Healthy ‘Low and High Gating' Humans and Relation to Psychometry

PubMed Central

Csomor, Philipp A; Preller, Katrin H; Geyer, Mark A; Studerus, Erich; Huber, Theodor; Vollenweider, Franz X

2014-01-01

Despite advances in the treatment of schizophrenia spectrum disorders with atypical antipsychotics (AAPs), there is still need for compounds with improved efficacy/side-effect ratios. Evidence from challenge studies suggests that the assessment of gating functions in humans and rodents with naturally low-gating levels might be a useful model to screen for novel compounds with antipsychotic properties. To further evaluate and extend this translational approach, three AAPs were examined. Compounds without antipsychotic properties served as negative control treatments. In a placebo-controlled, within-subject design, healthy males received either single doses of aripiprazole and risperidone (n=28), amisulpride and lorazepam (n=30), or modafinil and valproate (n=30), and placebo. Prepulse inhibiton (PPI) and P50 suppression were assessed. Clinically associated symptoms were evaluated using the SCL-90-R. Aripiprazole, risperidone, and amisulpride increased P50 suppression in low P50 gaters. Lorazepam, modafinil, and valproate did not influence P50 suppression in low gaters. Furthermore, low P50 gaters scored significantly higher on the SCL-90-R than high P50 gaters. Aripiprazole increased PPI in low PPI gaters, whereas modafinil and lorazepam attenuated PPI in both groups. Risperidone, amisulpride, and valproate did not influence PPI. P50 suppression in low gaters appears to be an antipsychotic-sensitive neurophysiologic marker. This conclusion is supported by the association of low P50 suppression and higher clinically associated scores. Furthermore, PPI might be sensitive for atypical mechanisms of antipsychotic medication. The translational model investigating differential effects of AAPs on gating in healthy subjects with naturally low gating can be beneficial for phase II/III development plans by providing additional information for critical decision making. PMID:24801767

Effect of respiratory and cardiac gating on the major diffusion-imaging metrics.

PubMed

Hamaguchi, Hiroyuki; Tha, Khin Khin; Sugimori, Hiroyuki; Nakanishi, Mitsuhiro; Nakagawa, Shin; Fujiwara, Taro; Yoshida, Hirokazu; Takamori, Sayaka; Shirato, Hiroki

2016-08-01

The effect of respiratory gating on the major diffusion-imaging metrics and that of cardiac gating on mean kurtosis (MK) are not known. For evaluation of whether the major diffusion-imaging metrics-MK, fractional anisotropy (FA), and mean diffusivity (MD) of the brain-varied between gated and non-gated acquisitions, respiratory-gated, cardiac-gated, and non-gated diffusion-imaging of the brain were performed in 10 healthy volunteers. MK, FA, and MD maps were constructed for all acquisitions, and the histograms were constructed. The normalized peak height and location of the histograms were compared among the acquisitions by use of Friedman and post hoc Wilcoxon tests. The effect of the repetition time (TR) on the diffusion-imaging metrics was also tested, and we corrected for its variation among acquisitions, if necessary. The results showed a shift in the peak location of the MK and MD histograms to the right with an increase in TR (p ≤ 0.01). The corrected peak location of the MK histograms, the normalized peak height of the FA histograms, the normalized peak height and the corrected peak location of the MD histograms varied significantly between the gated and non-gated acquisitions (p < 0.05). These results imply an influence of respiration and cardiac pulsation on the major diffusion-imaging metrics. The gating conditions must be kept identical if reproducible results are to be achieved. © The Author(s) 2016.

Facilitation of information processing in the primary somatosensory area in the ball rotation task.

PubMed

Wasaka, Toshiaki; Kida, Tetsuo; Kakigi, Ryusuke

2017-11-14

Somatosensory input to the brain is known to be modulated during voluntary movement. It has been demonstrated that the response in the primary somatosensory cortex (SI) is generally gated during simple movement of the corresponding body part. This study investigated sensorimotor integration in the SI during manual movement using a motor task combining movement complexity and object manipulation. While the amplitude of M20 and M30 generated in the SI showed a significant reduction during manual movement, the subsequent component (M38) was significantly higher in the motor task than in the stationary condition. Especially, that in the ball rotation task showed a significant enhancement compared with those in the ball grasping and stone and paper tasks. Although sensorimotor integration in the SI generally has an inhibitory effect on information processing, here we found facilitation. Since the ball rotation task seems to be increasing the demand for somatosensory information to control the complex movements and operate two balls in the palm, it may have resulted in an enhancement of M38 generated in the SI.

Cannabidiol Affects MK-801-Induced Changes in the PPI Learned Response of Capuchin Monkeys (Sapajus spp.).

PubMed

Saletti, Patricia G; Maior, Rafael S; Barros, Marilia; Nishijo, Hisao; Tomaz, Carlos

2017-01-01

There are several lines of evidence indicating a possible therapeutic action of cannabidiol (CBD) in schizophrenia treatment. Studies with rodents have demonstrated that CBD reverses MK-801 effects in prepulse inhibition (PPI) disruption, which may indicate that CBD acts by improving sensorimotor gating deficits. In the present study, we investigated the effects of CBD on a PPI learned response of capuchin monkeys ( Sapajus spp.). A total of seven monkeys were employed in this study. In Experiment 1, we evaluated the CBD (doses of 15, 30, 60 mg/kg, i.p.) effects on PPI. In Experiment 2, the effects of sub-chronic MK-801 (0.02 mg/kg, i.m.) on PPI were challenged by a CBD pre-treatment. No changes in PPI response were observed after CBD-alone administration. However, MK-801 increased the PPI response of our animals. CBD pre-treatment blocked the PPI increase induced by MK-801. Our findings suggest that CBD's reversal of the MK-801 effects on PPI is unlikely to stem from a direct involvement on sensorimotor mechanisms, but may possibly reflect its anxiolytic properties.

Accelerated recovery of sensorimotor function in a dog submitted to quasi-total transection of the cervical spinal cord and treated with PEG.

PubMed

Kim, C-Yoon; Hwang, In-Kyu; Kim, Hana; Jang, Se-Woong; Kim, Hong Seog; Lee, Won-Young

2016-01-01

A case report on observing the recovery of sensory-motor function after cervical spinal cord transection. Laminectomy and transection of cervical spinal cord (C5) was performed on a male beagle weighing 3.5 kg. After applying polyethylene glycol (PEG) on the severed part, reconstruction of cervical spinal cord was confirmed by the restoration of sensorimotor function. Tetraplegia was observed immediately after operation, however, the dog showed stable respiration and survival without any complication. The dog showed fast recovery after 1 week, and recovered approximately 90% of normal sensorimotor function 3 weeks after the operation, although urinary disorder was still present. All recovery stages were recorded by video camera twice a week for behavioral analysis. While current belief holds that functional recovery is impossible after a section greater than 50% at C5-6 in the canine model, this case study shows the possibility of cervical spinal cord reconstruction after near-total transection. Furthermore, this case study also confirms that PEG can truly expedite the recovery of sensorimotor function after cervical spinal cord sections in dogs.

Brain-computer interface signal processing at the Wadsworth Center: mu and sensorimotor beta rhythms.

PubMed

McFarland, Dennis J; Krusienski, Dean J; Wolpaw, Jonathan R

2006-01-01

The Wadsworth brain-computer interface (BCI), based on mu and beta sensorimotor rhythms, uses one- and two-dimensional cursor movement tasks and relies on user training. This is a real-time closed-loop system. Signal processing consists of channel selection, spatial filtering, and spectral analysis. Feature translation uses a regression approach and normalization. Adaptation occurs at several points in this process on the basis of different criteria and methods. It can use either feedforward (e.g., estimating the signal mean for normalization) or feedback control (e.g., estimating feature weights for the prediction equation). We view this process as the interaction between a dynamic user and a dynamic system that coadapt over time. Understanding the dynamics of this interaction and optimizing its performance represent a major challenge for BCI research.

Localized N20 Component of Somatosensory Evoked Magnetic Fields in Frontoparietal Brain Tumor Patients Using Noise-Normalized Approaches.

PubMed

Elaina, Nor Safira; Malik, Aamir Saeed; Shams, Wafaa Khazaal; Badruddin, Nasreen; Abdullah, Jafri Malin; Reza, Mohammad Faruque

2018-06-01

To localize sensorimotor cortical activation in 10 patients with frontoparietal tumors using quantitative magnetoencephalography (MEG) with noise-normalized approaches. Somatosensory evoked magnetic fields (SEFs) were elicited in 10 patients with somatosensory tumors and in 10 control participants using electrical stimulation of the median nerve via the right and left wrists. We localized the N20m component of the SEFs using dynamic statistical parametric mapping (dSPM) and standardized low-resolution brain electromagnetic tomography (sLORETA) combined with 3D magnetic resonance imaging (MRI). The obtained coordinates were compared between groups. Finally, we statistically evaluated the N20m parameters across hemispheres using non-parametric statistical tests. The N20m sources were accurately localized to Brodmann area 3b in all members of the control group and in seven of the patients; however, the sources were shifted in three patients relative to locations outside the primary somatosensory cortex (SI). Compared with the affected (tumor) hemispheres in the patient group, N20m amplitudes and the strengths of the current sources were significantly lower in the unaffected hemispheres and in both hemispheres of the control group. These results were consistent for both dSPM and sLORETA approaches. Tumors in the sensorimotor cortex lead to cortical functional reorganization and an increase in N20m amplitude and current-source strengths. Noise-normalized approaches for MEG analysis that are integrated with MRI show accurate and reliable localization of sensorimotor function.

The Association of Schizophrenia Risk -Amino Acid Oxidase Polymorphisms With Sensorimotor Gating, Working Memory and Personality in Healthy Males

PubMed Central

Roussos, Panos; Giakoumaki, Stella G; Adamaki, Eva; Anastasios, Georgakopoulos; Nikos, Robakis K; Bitsios, Panos

2011-01-01

There is evidence supporting a role for the -amino acid oxidase (DAO) locus in schizophrenia. This study aimed to determine the relationship of five single-nucleotide polymorphisms (SNPs) within the DAO gene identified as promising schizophrenia risk genes (rs4623951, rs2111902, rs3918346, rs3741775, and rs3825251) to acoustic startle, prepulse inhibition (PPI), working memory, and personality dimensions. A highly homogeneous study entry cohort (n=530) of healthy, young male army conscripts (n=703) originating from the Greek LOGOS project (Learning On Genetics Of Schizophrenia Spectrum) underwent PPI of the acoustic startle reflex, working memory, and personality assessment. The QTPHASE from the UNPHASED package was used for the association analysis of each SNP or haplotype data, with p-values corrected for multiple testing by running 10 000 permutations of the data. The rs4623951_T-rs3741775_G and rs4623951_T-rs2111902_T diplotypes were associated with reduced PPI and worse performance in working memory tasks and a personality pattern characterized by attenuated anxiety. Median stratification analysis of the risk diplotype group (ie, those individuals homozygous for the T and G alleles (TG+)) showed reduced PPI and working memory performance only in TG+ individuals with high trait anxiety. The rs4623951_T allele, which is the DAO polymorphism most strongly associated with schizophrenia, might tag a haplotype that affects PPI, cognition, and personality traits in general population. Our findings suggest an influence of the gene in the neural substrate mediating sensorimotor gating and working memory, especially when combined with high anxiety and further validate DAO as a candidate gene for schizophrenia and spectrum disorders. PMID:21471957

Increased sensorimotor gating in recreational and dependent cocaine users is modulated by craving and attention-deficit/hyperactivity disorder symptoms.

PubMed

Preller, Katrin H; Ingold, Nina; Hulka, Lea M; Vonmoos, Matthias; Jenni, Daniela; Baumgartner, Markus R; Vollenweider, Franz X; Quednow, Boris B

2013-02-01

Cocaine dependence has been associated with blunted dopamine and norepinephrine signaling, but it is unknown if recreational cocaine use is also associated with alterations of catecholamine systems. Prepulse inhibition (PPI) of the acoustic startle response-a measure of sensorimotor gating-is highly sensitive for manipulations of the catecholamine system. Therefore, we investigated whether relatively pure recreational users (RCU) and dependent cocaine users (DCU) display alterations of PPI, startle reactivity, and habituation. Moreover, the influences of methylenedioxymethamphetamine and cannabis co-use, craving, and attention-deficit/hyperactivity disorder (ADHD) symptoms on startle measures were examined. In 64 RCU, 29 DCU, and 66 stimulant-naïve control subjects, PPI of acoustic startle response, startle reactivity, habituation, ADHD symptoms, and cocaine craving were assessed. Drug use of all participants was controlled by hair and urine toxicologies. Both RCU and DCU showed increased PPI in comparison with control participants (Cohen's d=.38 and d=.67, respectively), while RCU and DCU did not differ in PPI measures (d=.12). No significant group differences were found in startle reactivity or habituation measures. In cocaine users, PPI was positively correlated with cumulative cocaine dose used, craving for cocaine, and ADHD symptoms. Users with a diagnosis of ADHD and strong craving symptoms displayed the highest PPI levels compared with control subjects (d=.78). The augmented PPI in RCU and DCU suggests that recreational use of cocaine is associated with altered catecholamine signaling, in particular if ADHD or craving symptoms are present. Finally, ADHD might be a critical risk factor for cocaine-induced changes of the catecholamine system. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Interactions between cannabidiol and Δ9-THC following acute and repeated dosing: Rebound hyperactivity, sensorimotor gating and epigenetic and neuroadaptive changes in the mesolimbic pathway.

PubMed

Todd, Stephanie M; Zhou, Cilla; Clarke, David J; Chohan, Tariq W; Bahceci, Dilara; Arnold, Jonathon C

2017-02-01

The evidence base for the use of medical cannabis preparations containing specific ratios of cannabidiol (CBD) and Δ 9 -tetrahydrocannabinol (THC) is limited. While there is abundant data on acute interactions between CBD and THC, few studies have assessed the impact of their repeated co-administration. We previously reported that CBD inhibited or potentiated the acute effects of THC dependent on the measure being examined at a 1:1 CBD:THC dose ratio. Further, CBD decreased THC effects on brain regions involved in memory, anxiety and body temperature regulation. Here we extend on these finding by examining over 15 days of treatment whether CBD modulated the repeated effects of THC on behaviour and neuroadaption markers in the mesolimbic dopamine pathway. After acute locomotor suppression, repeated THC caused rebound locomotor hyperactivity that was modestly inhibited by CBD. CBD also slightly reduced the acute effects of THC on sensorimotor gating. These subtle effects were found at a 1:1 CBD:THC dose ratio but were not accentuated by a 5:1 dose ratio. CBD did not alter the trajectory of enduring THC-induced anxiety nor tolerance to the pharmacological effects of THC. There was no evidence of CBD potentiating the behavioural effects of THC. However we demonstrated for the first time that repeated co-administration of CBD and THC increased histone 3 acetylation (H3K9/14ac) in the VTA and ΔFosB expression in the nucleus accumbens. These changes suggest that while CBD may have protective effects acutely, its long-term molecular actions on the brain are more complex and may be supradditive. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Hearing Loss in a Mouse Model of 22q11.2 Deletion Syndrome

PubMed Central

Fuchs, Jennifer C.; Zinnamon, Fhatarah A.; Taylor, Ruth R.; Ivins, Sarah; Scambler, Peter J.; Forge, Andrew; Tucker, Abigail S.; Linden, Jennifer F.

2013-01-01

22q11.2 Deletion Syndrome (22q11DS) arises from an interstitial chromosomal microdeletion encompassing at least 30 genes. This disorder is one of the most significant known cytogenetic risk factors for schizophrenia, and can also cause heart abnormalities, cognitive deficits, hearing difficulties, and a variety of other medical problems. The Df1/+ hemizygous knockout mouse, a model for human 22q11DS, recapitulates many of the deficits observed in the human syndrome including heart defects, impaired memory, and abnormal auditory sensorimotor gating. Here we show that Df1/+ mice, like human 22q11DS patients, have substantial rates of hearing loss arising from chronic middle ear infection. Auditory brainstem response (ABR) measurements revealed significant elevation of click-response thresholds in 48% of Df1/+ mice, often in only one ear. Anatomical and histological analysis of the middle ear demonstrated no gross structural abnormalities, but frequent signs of otitis media (OM, chronic inflammation of the middle ear), including excessive effusion and thickened mucosa. In mice for which both in vivo ABR thresholds and post mortem middle-ear histology were obtained, the severity of signs of OM correlated directly with the level of hearing impairment. These results suggest that abnormal auditory sensorimotor gating previously reported in mouse models of 22q11DS could arise from abnormalities in auditory processing. Furthermore, the findings indicate that Df1/+ mice are an excellent model for increased risk of OM in human 22q11DS patients. Given the frequently monaural nature of OM in Df1/+ mice, these animals could also be a powerful tool for investigating the interplay between genetic and environmental causes of OM. PMID:24244619

Hearing loss in a mouse model of 22q11.2 Deletion Syndrome.

PubMed

Fuchs, Jennifer C; Zinnamon, Fhatarah A; Taylor, Ruth R; Ivins, Sarah; Scambler, Peter J; Forge, Andrew; Tucker, Abigail S; Linden, Jennifer F

2013-01-01

22q11.2 Deletion Syndrome (22q11DS) arises from an interstitial chromosomal microdeletion encompassing at least 30 genes. This disorder is one of the most significant known cytogenetic risk factors for schizophrenia, and can also cause heart abnormalities, cognitive deficits, hearing difficulties, and a variety of other medical problems. The Df1/+ hemizygous knockout mouse, a model for human 22q11DS, recapitulates many of the deficits observed in the human syndrome including heart defects, impaired memory, and abnormal auditory sensorimotor gating. Here we show that Df1/+ mice, like human 22q11DS patients, have substantial rates of hearing loss arising from chronic middle ear infection. Auditory brainstem response (ABR) measurements revealed significant elevation of click-response thresholds in 48% of Df1/+ mice, often in only one ear. Anatomical and histological analysis of the middle ear demonstrated no gross structural abnormalities, but frequent signs of otitis media (OM, chronic inflammation of the middle ear), including excessive effusion and thickened mucosa. In mice for which both in vivo ABR thresholds and post mortem middle-ear histology were obtained, the severity of signs of OM correlated directly with the level of hearing impairment. These results suggest that abnormal auditory sensorimotor gating previously reported in mouse models of 22q11DS could arise from abnormalities in auditory processing. Furthermore, the findings indicate that Df1/+ mice are an excellent model for increased risk of OM in human 22q11DS patients. Given the frequently monaural nature of OM in Df1/+ mice, these animals could also be a powerful tool for investigating the interplay between genetic and environmental causes of OM.

Psychotomimetic effects of different doses of MK-801 and the underlying mechanisms in a selective memory impairment model.

PubMed

Liu, Weiqing; Wang, Dong; Hong, Wenjuan; Yu, Yi; Tang, Jinsong; Wang, Jicai; Liu, Fang; Xu, Xiufeng; Tan, Liwen; Chen, Xiaogang

2017-03-01

Although N-methyl-d-aspartate receptor antagonists-induced hypoglutamate rodent models are the most well-established models for preclinical studies of schizophrenia-related deficits, they also evoke a wide spectrum of psychotomimetic side effects. It is significant to increase the specificity of hypoglutamate rodent models. In this study, the recognition memory was evaluated in rats by object recognition test (ORT), sensorimotor gating was evaluated by prepulse inhibition of the startle reflex (PPI), and locomotor activity was measured using open field test. High-performance liquid chromatography was used to measure neurotransmitters content in the medial prefrontal cortex (mPFC) and thalamus (THA). Total Akt and phospho-Akt protein was measured by Western blots. Results showed that 0.3mg/kg of MK-801 was most effective in inducing locomotion. 0.3mg/kg of MK-801 was most effective in decreasing PPI. 0.03mg/kg of MK-801 was most effective in decreasing object memory while not affecting exploration manners in the training session. 0.03mg/kg of MK-801 significantly increased HVA and Glu content in the mPFC. 0.1mg/kg of MK-801 significantly decreased GABA content in the THA. 0.03mg/kg of MK-801 significantly decreased Akt phosphorylation in the mPFC, which was related to the ORT index. In conclusion, a dose of 0.03mg/kg MK-801 can establish a "pure" memory impairment model without contaminations of sensorimotor gating and locomotor activity. MK-801-induced cognitive deficits is associated with increased DA metabolites and glutamate content in the mPFC and decreased GABA content in the THA as well as decrease in Akt phosphorylation in the mPFC. Copyright © 2016. Published by Elsevier B.V.

Effects of aberrant gamma frequency oscillations on prepulse inhibition.

PubMed

Jones, Nigel C; Anderson, Paul; Rind, Gil; Sullivan, Caley; van den Buuse, Maarten; O'Brien, Terence J

2014-10-01

Emerging literature implicates abnormalities in gamma frequency oscillations in the pathophysiology of schizophrenia, with hypofunction of N-methyl-D-aspartate (NMDA) receptors implicated as a key factor. Prepulse inhibition (PPI) is a behavioural measure of sensorimotor gating, which is disrupted in schizophrenia. We studied relationships between ongoing and sensory-evoked gamma oscillations and PPI using pharmacological interventions designed to increase gamma oscillations (ketamine, MK-801); reduce gamma oscillations (LY379268); or disrupt PPI (amphetamine). We predicted that elevating ongoing gamma power would lead to increased 'neural noise' in cortical circuits, dampened sensory-evoked gamma responses and disrupted behaviour. Wistar rats were implanted with EEG recording electrodes. They received ketamine (5 mg/kg), MK-801 (0.16 mg/kg), amphetamine (0.5 mg/kg), LY379268 (3 mg/kg) or vehicle and underwent PPI sessions with concurrent EEG recording. Ketamine and MK-801 increased the power of ongoing gamma oscillations and caused time-matched disruptions of PPI, while amphetamine marginally affected ongoing gamma power. In contrast, LY379268 reduced ongoing gamma power, but had no effect on PPI. The sensory gamma response evoked by the prepulse was reduced following treatment with all psychotomimetics, associating with disruptions in PPI. This was most noticeable following treatment with NMDA receptor antagonists. We found that ketamine and MK-801 increase ongoing gamma power and reduce evoked gamma power, both of which are related to disruptions in sensorimotor gating. This appears to be due to antagonism of NMDA receptors, since amphetamine and LY379268 differentially impacted these outcomes and possess different neuropharmacological substrates. Aberrant gamma frequency oscillations caused by NMDA receptor hypofunction may mediate the sensory processing deficits observed in schizophrenia.

Step buffer layer of Al0.25Ga0.75N/Al0.08Ga0.92N on P-InAlN gate normally-off high electron mobility transistors

NASA Astrophysics Data System (ADS)

Shrestha, Niraj M.; Li, Yiming; Chang, E. Y.

2016-07-01

Normally-off AlGaN/GaN high electron mobility transistors (HEMTs) are indispensable devices for power electronics as they can greatly simplify circuit designs in a cost-effective way. In this work, the electrical characteristics of p-type InAlN gate normally-off AlGaN/GaN HEMTs with a step buffer layer of Al0.25Ga0.75N/Al0.1Ga0.9N is studied numerically. Our device simulation shows that a p-InAlN gate with a step buffer layer allows the transistor to possess normally-off behavior with high drain current and high breakdown voltage simultaneously. The gate modulation by the p-InAlN gate and the induced holes appearing beneath the gate at the GaN/Al0.25Ga0.75N interface is because a hole appearing in the p-InAlN layer can effectively vary the threshold voltage positively. The estimated threshold voltage of the normally-off HEMTs explored is 2.5 V at a drain bias of 25 V, which is 220% higher than the conventional p-AlGaN normally-off AlGaN/GaN gate injection transistor (GIT). Concurrently, the maximum current density of the explored HEMT at a drain bias of 10 V slightly decreases by about 7% (from 240 to 223 mA mm-1). At a drain bias of 15 V, the current density reached 263 mA mm-1. The explored structure is promising owing to tunable positive threshold voltage and the maintenance of similar current density; notably, its breakdown voltage significantly increases by 36% (from 800 V, GIT, to 1086 V). The engineering findings of this study indicate that novel p-InAlN for both the gate and the step buffer layer can feature a high threshold voltage, large current density and high operating voltage for advanced AlGaN/GaN HEMT devices.

Evaluation of normal lung tissue complication probability in gated and conventional radiotherapy using the 4D XCAT digital phantom.

PubMed

Shahzadeh, Sara; Gholami, Somayeh; Aghamiri, Seyed Mahmood Reza; Mahani, Hojjat; Nabavi, Mansoure; Kalantari, Faraz

2018-06-01

The present study was conducted to investigate normal lung tissue complication probability in gated and conventional radiotherapy (RT) as a function of diaphragm motion, lesion size, and its location using 4D-XCAT digital phantom in a simulation study. Different time series of 3D-CT images were generated using the 4D-XCAT digital phantom. The binary data obtained from this phantom were then converted to the digital imaging and communication in medicine (DICOM) format using an in-house MATLAB-based program to be compatible with our treatment planning system (TPS). The 3D-TPS with superposition computational algorithm was used to generate conventional and gated plans. Treatment plans were generated for 36 different XCAT phantom configurations. These included four diaphragm motions of 20, 25, 30 and 35 mm, three lesion sizes of 3, 4, and 5 cm in diameter and each tumor was placed in four different lung locations (right lower lobe, right upper lobe, left lower lobe and left upper lobe). The complication of normal lung tissue was assessed in terms of mean lung dose (MLD), the lung volume receiving ≥20 Gy (V20), and normal tissue complication probability (NTCP). The results showed that the gated RT yields superior outcomes in terms of normal tissue complication compared to the conventional RT. For all cases, the gated radiation therapy technique reduced the mean dose, V20, and NTCP of lung tissue by up to 5.53 Gy, 13.38%, and 23.89%, respectively. The results of this study showed that the gated RT provides significant advantages in terms of the normal lung tissue complication, compared to the conventional RT, especially for the lesions near the diaphragm. Copyright © 2018 Elsevier Ltd. All rights reserved.

The effect of rTMS over the inferior parietal lobule on EEG sensorimotor reactivity differs according to self-reported traits of autism in typically developing individuals.

PubMed

Puzzo, Ignazio; Cooper, Nicholas R; Cantarella, Simona; Fitzgerald, Paul B; Russo, Riccardo

2013-12-06

Previous research suggested that EEG markers of mirror neuron system activation may differ, in the normal population as a function of different levels of the autistic spectrum quotient; (AQ). The present study aimed at modulating the EEG sensorimotor reactivity induced by hand movement observation by means of repetitive transcranial magnetic stimulation (rTMS) applied to the inferior parietal lobule. We examined how the resulting rTMS modulation differed in relation to the self-reported autistic traits in the typically developing population. Results showed that during sham stimulation, all participants had significantly greater sensorimotor alpha reactivity (motor cortex-C electrodes) when observing hand movements compared to static hands. This sensorimotor alpha reactivity difference was reduced during active rTMS stimulation. Results also revealed that in the average AQ group at sham there was a significant increase in low beta during hand movement than static hand observation (pre-motor areas-FC electrodes) and that (like alpha over the C electrodes) this difference is abolished when active rTMS is delivered. Participants with high AQ scores showed no significant difference in low beta sensorimotor reactivity between active and sham rTMS during static hand or hand movement observation. These findings suggest that unlike sham, active rTMS over the IPL modulates the oscillatory activity of the low beta frequency of a distal area, namely the anterior sector of the sensorimotor cortex, when participants observe videos of static hand. Importantly, this modulation differs according to the degree of self-reported traits of autism in a typically developing population. © 2013 Elsevier B.V. All rights reserved.

The Effects of Fluency Enhancing Conditions on Sensorimotor Control of Speech in Typically Fluent Speakers: An EEG Mu Rhythm Study

PubMed Central

Kittilstved, Tiffani; Reilly, Kevin J.; Harkrider, Ashley W.; Casenhiser, Devin; Thornton, David; Jenson, David E.; Hedinger, Tricia; Bowers, Andrew L.; Saltuklaroglu, Tim

2018-01-01

Objective: To determine whether changes in sensorimotor control resulting from speaking conditions that induce fluency in people who stutter (PWS) can be measured using electroencephalographic (EEG) mu rhythms in neurotypical speakers. Methods: Non-stuttering (NS) adults spoke in one control condition (solo speaking) and four experimental conditions (choral speech, delayed auditory feedback (DAF), prolonged speech and pseudostuttering). Independent component analysis (ICA) was used to identify sensorimotor μ components from EEG recordings. Time-frequency analyses measured μ-alpha (8–13 Hz) and μ-beta (15–25 Hz) event-related synchronization (ERS) and desynchronization (ERD) during each speech condition. Results: 19/24 participants contributed μ components. Relative to the control condition, the choral and DAF conditions elicited increases in μ-alpha ERD in the right hemisphere. In the pseudostuttering condition, increases in μ-beta ERD were observed in the left hemisphere. No differences were present between the prolonged speech and control conditions. Conclusions: Differences observed in the experimental conditions are thought to reflect sensorimotor control changes. Increases in right hemisphere μ-alpha ERD likely reflect increased reliance on auditory information, including auditory feedback, during the choral and DAF conditions. In the left hemisphere, increases in μ-beta ERD during pseudostuttering may have resulted from the different movement characteristics of this task compared with the solo speaking task. Relationships to findings in stuttering are discussed. Significance: Changes in sensorimotor control related feedforward and feedback control in fluency-enhancing speech manipulations can be measured using time-frequency decompositions of EEG μ rhythms in neurotypical speakers. This quiet, non-invasive, and temporally sensitive technique may be applied to learn more about normal sensorimotor control and fluency enhancement in PWS. PMID:29670516

Targeting Dyrk1A with AAVshRNA Attenuates Motor Alterations in TgDyrk1A, a Mouse Model of Down Syndrome

PubMed Central

Ortiz-Abalia, Jon; Sahún, Ignasi; Altafaj, Xavier; Andreu, Núria; Estivill, Xavier; Dierssen, Mara; Fillat, Cristina

2008-01-01

Genetic-dissection studies carried out with Down syndrome (DS) murine models point to the critical contribution of Dyrk1A overexpression to the motor abnormalities and cognitive deficits displayed in DS individuals. In the present study we have used a murine model overexpressing Dyrk1A (TgDyrk1A mice) to evaluate whether functional CNS defects could be corrected with an inhibitory RNA against Dyrk1A, delivered by bilateral intrastriatal injections of adeno-associated virus type 2 (AAVshDyrk1A). We report that AAVshDyrk1A efficiently transduced HEK293 cells and primary neuronal cultures, triggering the specific inhibition of Dyrk1A expression. Injecting the vector into the striata of TgDyrk1A mice resulted in a restricted, long-term transduction of the striatum. This gene therapy was found to be devoid of toxicity and succeeded in normalizing Dyrk1A protein levels in TgDyrk1A mice. Importantly, the behavioral studies of the adult TgDyrk1A mice treated showed a reversal of corticostriatal-dependent phenotypes, as revealed by the attenuation of their hyperactive behavior, the restoration of motor-coordination defects, and an improvement in sensorimotor gating. Taken together, the data demonstrate that normalizing Dyrk1A gene expression in the striatum of adult TgDyrk1A mice, by means of AAVshRNA, clearly reverses motor impairment. Furthermore, these results identify Dyrk1A as a potential target for therapy in DS. PMID:18940310

Changes in sensorimotor-related thalamic diffusion properties and cerebrospinal fluid hydrodynamics predict gait responses to tap test in idiopathic normal-pressure hydrocephalus.

PubMed

Tsai, Ping-Huei; Chen, Yung-Chieh; Chiang, Shih-Wei; Huang, Teng-Yi; Chou, Ming-Chung; Liu, Hua-Shan; Chung, Hsiao-Wen; Peng, Giia-Sheun; Ma, Hsin-I; Kao, Hung-Wen; Chen, Cheng-Yu

2018-05-07

To compare diffusion tensor (DT)-derived indices from the thalamic nuclei and cerebrospinal fluid (CSF) hydrodynamic parameters for the prediction of gait responsiveness to the CSF tap test in early iNPH patients. In this study, 22 patients with iNPH and 16 normal controls were enrolled with the approval of an institutional review board. DT imaging and phase-contrast magnetic resonance imaging were performed in patients and controls to determine DT-related indices of the sensorimotor-related thalamic nuclei and CSF hydrodynamics. Gait performance was assessed in patients using gait scale before and after the tap test. The Mann-Whitney U test and receiver operating characteristic (ROC) curve analysis were applied to compare group differences between patients and controls and assess the predictive performance of gait responsiveness to the tap test in the patients. Fractional anisotropy (FA) and axial diffusivity showed significant increases in the ventrolateral (VL) and ventroposterolateral (VPL) nuclei of the iNPH group compared with those of the control group (p < 0.05). The predictions of gait responsiveness of ventral thalamic FA alone (area under the ROC curve [AUC] < 0.8) significantly outperformed those of CSF hydrodynamics alone (AUC < 0.6). The AUC curve was elevated to 0.812 when the CSF peak systolic velocity and FA value were combined for the VPL nucleus, yielding the highest sensitivity (0.769) and specificity (0.778) to predict gait responses. Combined measurements of sensorimotor-related thalamic FA and CSF hydrodynamics can provide potential biomarkers for gait response to the CSF tap test in patients with iNPH. • Ventrolateral and ventroposterolateral thalamic FA may predict gait responsiveness to tap test. • Thalamic neuroplasticity can be assessed through DTI in idiopathic normal-pressure hydrocephalus. • Changes in the CST associated with gait control could trigger thalamic neuroplasticity. • Activities of sensorimotor-related circuits could alter in patients with gait disturbance. • Management of patients with iNPH could be more appropriate.

Normal and abnormal human vestibular ocular function

NASA Technical Reports Server (NTRS)

Peterka, R. J.; Black, F. O.

1986-01-01

The major motivation of this research is to understand the role the vestibular system plays in sensorimotor interactions which result in spatial disorientation and motion sickness. A second goal was to explore the range of abnormality as it is reflected in quantitative measures of vestibular reflex responses. The results of a study of vestibular reflex measurements in normal subjects and preliminary results in abnormal subjects are presented in this report. Statistical methods were used to define the range of normal responses, and determine age related changes in function.

Auditory word identification in dyslexic and normally achieving readers.

PubMed

Bruno, Jennifer L; Manis, Franklin R; Keating, Patricia; Sperling, Anne J; Nakamoto, Jonathan; Seidenberg, Mark S

2007-07-01

The integrity of phonological representation/processing in dyslexic children was explored with a gating task in which children listened to successively longer segments (gates) of a word. At each gate, the task was to decide what the entire word was. Responses were scored for overall accuracy as well as the children's sensitivity to coarticulation from the final consonant. As a group, dyslexic children were less able than normally achieving readers to detect coarticulation present in the vowel portion of the word, particularly on the most difficult items, namely those ending in a nasal sound. Hierarchical regression and path analyses indicated that phonological awareness mediated the relation of gating and general language ability to word and pseudoword reading ability.

In vivo magnetic resonance spectroscopy measurement of gray-matter and white-matter gamma-aminobutyric acid concentration in sensorimotor cortex using a motion-controlled MEGA point-resolved spectroscopy sequence.

PubMed

Bhattacharyya, Pallab K; Phillips, Micheal D; Stone, Lael A; Lowe, Mark J

2011-04-01

Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the brain. Understanding the GABA concentration, in vivo, is important to understand normal brain function. Using MEGA point-resolved spectroscopy sequence with interleaved water scans to detect subject motion, GABA level of sensorimotor cortex was measured using a voxel identified from a functional magnetic resonance imaging scan. The GABA level in a 20×20×20-mm(3) voxel consisting of 37%±7% gray matter, 52%±12% white matter and 11%±8% cerebrospinal fluid in the sensorimotor region was measured to be 1.43±0.48 mM. In addition, using linear regression analysis, GABA concentrations within gray and white matter were calculated to be 2.87±0.61 and 0.33±0.11 mM, respectively. Copyright © 2011 Elsevier Inc. All rights reserved.

An “ohmic-first” self-terminating gate-recess technique for normally-off Al2O3/GaN MOSFET

NASA Astrophysics Data System (ADS)

Wang, Hongyue; Wang, Jinyan; Li, Mengjun; He, Yandong; Wang, Maojun; Yu, Min; Wu, Wengang; Zhou, Yang; Dai, Gang

2018-04-01

In this article, an ohmic-first AlGaN/GaN self-terminating gate-recess etching technique was demonstrated where ohmic contact formation is ahead of gate-recess-etching/gate-dielectric-deposition (GRE/GDD) process. The ohmic contact exhibits few degradations after the self-terminating gate-recess process. Besides, when comparing with that using the conventional fabrication process, the fabricated device using the ohmic-first fabrication process shows a better gate dielectric quality in terms of more than 3 orders lower forward gate leakage current, more than twice higher reverse breakdown voltage as well as better stability. Based on this proposed technique, the normally-off Al2O3/GaN MOSFET exhibits a threshold voltage (V th) of ˜1.8 V, a maximum drain current of ˜328 mA/mm, a forward gate leakage current of ˜10-6 A/mm and an off-state breakdown voltage of 218 V at room temperature. Meanwhile, high temperature characteristics of the device was also evaluated and small variations (˜7.6%) of the threshold voltage was confirmed up to 300 °C.

Measurement and modification of the EEG and related behavior

NASA Technical Reports Server (NTRS)

Sterman, M. B.

1991-01-01

Electrophysiological changes in the sensorimotor pathways were found to accompany the effect of rhythmic EEG patterns in the sensorimotor cortex. Additionally, several striking behavioral changes were seen, including in particular an enhancement of sleep and an elevation of seizure threshold to epileptogenic agents. This raised the possibility that human seizure disorders might be influenced therapeutically by similar training. Our objective in human EEG feedback training became not only the facilitation of normal rhythmic patterns, but also the suppression of abnormal activity, thus requiring complex contingencies directed to the normalization of the sensorimotor EEG. To achieve this, a multicomponent frequency analysis was developed to extract and separate normal and abnormal elements of the EEG signal. Each of these elements was transduced to a specific component of a visual display system, and these were combined through logic circuits to present the subject with a symbolic display. Variable criteria provided for the gradual shaping of EEG elements towards the desired normal pattern. Some 50-70% of patients with poorly controlled seizure disorders experienced therapeutic benefits from this approach in our laboratory, and subsequently in many others. A more recent application of this approach to the modification of human brain function in our lab has been directed to the dichotomous problems of task overload and underload in the contemporary aviation environment. At least 70% of all aviation accidents have been attributed to the impact of these kinds of problems on crew performance. The use of EEG in this context has required many technical innovations and the application of the latest advances in EEG signal analysis. Our first goal has been the identification of relevant EEG characteristics. Additionally, we have developed a portable recording and analysis system for application in this context. Findings from laboratory and in-flight studies suggest that we will be able to detect appropriate changes in brain function, and feed this information to on-board computers for modification of mission requirements and/or crew status.

Human Subthalamic Nucleus in Movement Error Detection and Its Evaluation during Visuomotor Adaptation

PubMed Central

Zavala, Baltazar; Pogosyan, Alek; Ashkan, Keyoumars; Zrinzo, Ludvic; Foltynie, Thomas; Limousin, Patricia; Brown, Peter

2014-01-01

Monitoring and evaluating movement errors to guide subsequent movements is a critical feature of normal motor control. Previously, we showed that the postmovement increase in electroencephalographic (EEG) beta power over the sensorimotor cortex reflects neural processes that evaluate motor errors consistent with Bayesian inference (Tan et al., 2014). Whether such neural processes are limited to this cortical region or involve the basal ganglia is unclear. Here, we recorded EEG over the cortex and local field potential (LFP) activity in the subthalamic nucleus (STN) from electrodes implanted in patients with Parkinson's disease, while they moved a joystick-controlled cursor to visual targets displayed on a computer screen. After movement offsets, we found increased beta activity in both local STN LFP and sensorimotor cortical EEG and in the coupling between the two, which was affected by both error magnitude and its contextual saliency. The postmovement increase in the coupling between STN and cortex was dominated by information flow from sensorimotor cortex to STN. However, an information drive appeared from STN to sensorimotor cortex in the first phase of the adaptation, when a constant rotation was applied between joystick inputs and cursor outputs. The strength of the STN to cortex drive correlated with the degree of adaption achieved across subjects. These results suggest that oscillatory activity in the beta band may dynamically couple the sensorimotor cortex and basal ganglia after movements. In particular, beta activity driven from the STN to cortex indicates task-relevant movement errors, information that may be important in modifying subsequent motor responses. PMID:25505327

Emergence of Functional Hierarchy in a Multiple Timescale Neural Network Model: A Humanoid Robot Experiment

PubMed Central

Yamashita, Yuichi; Tani, Jun

2008-01-01

It is generally thought that skilled behavior in human beings results from a functional hierarchy of the motor control system, within which reusable motor primitives are flexibly integrated into various sensori-motor sequence patterns. The underlying neural mechanisms governing the way in which continuous sensori-motor flows are segmented into primitives and the way in which series of primitives are integrated into various behavior sequences have, however, not yet been clarified. In earlier studies, this functional hierarchy has been realized through the use of explicit hierarchical structure, with local modules representing motor primitives in the lower level and a higher module representing sequences of primitives switched via additional mechanisms such as gate-selecting. When sequences contain similarities and overlap, however, a conflict arises in such earlier models between generalization and segmentation, induced by this separated modular structure. To address this issue, we propose a different type of neural network model. The current model neither makes use of separate local modules to represent primitives nor introduces explicit hierarchical structure. Rather than forcing architectural hierarchy onto the system, functional hierarchy emerges through a form of self-organization that is based on two distinct types of neurons, each with different time properties (“multiple timescales”). Through the introduction of multiple timescales, continuous sequences of behavior are segmented into reusable primitives, and the primitives, in turn, are flexibly integrated into novel sequences. In experiments, the proposed network model, coordinating the physical body of a humanoid robot through high-dimensional sensori-motor control, also successfully situated itself within a physical environment. Our results suggest that it is not only the spatial connections between neurons but also the timescales of neural activity that act as important mechanisms leading to functional hierarchy in neural systems. PMID:18989398

Genetic Mapping in Mice Reveals the Involvement of Pcdh9 in Long-Term Social and Object Recognition and Sensorimotor Development.

PubMed

Bruining, Hilgo; Matsui, Asuka; Oguro-Ando, Asami; Kahn, René S; Van't Spijker, Heleen M; Akkermans, Guus; Stiedl, Oliver; van Engeland, Herman; Koopmans, Bastijn; van Lith, Hein A; Oppelaar, Hugo; Tieland, Liselotte; Nonkes, Lourens J; Yagi, Takeshi; Kaneko, Ryosuke; Burbach, J Peter H; Yamamoto, Nobuhiko; Kas, Martien J

2015-10-01

Quantitative genetic analysis of basic mouse behaviors is a powerful tool to identify novel genetic phenotypes contributing to neurobehavioral disorders. Here, we analyzed genetic contributions to single-trial, long-term social and nonsocial recognition and subsequently studied the functional impact of an identified candidate gene on behavioral development. Genetic mapping of single-trial social recognition was performed in chromosome substitution strains, a sophisticated tool for detecting quantitative trait loci (QTL) of complex traits. Follow-up occurred by generating and testing knockout (KO) mice of a selected QTL candidate gene. Functional characterization of these mice was performed through behavioral and neurological assessments across developmental stages and analyses of gene expression and brain morphology. Chromosome substitution strain 14 mapping studies revealed an overlapping QTL related to long-term social and object recognition harboring Pcdh9, a cell-adhesion gene previously associated with autism spectrum disorder. Specific long-term social and object recognition deficits were confirmed in homozygous (KO) Pcdh9-deficient mice, while heterozygous mice only showed long-term social recognition impairment. The recognition deficits in KO mice were not associated with alterations in perception, multi-trial discrimination learning, sociability, behavioral flexibility, or fear memory. Rather, KO mice showed additional impairments in sensorimotor development reflected by early touch-evoked biting, rotarod performance, and sensory gating deficits. This profile emerged with structural changes in deep layers of sensory cortices, where Pcdh9 is selectively expressed. This behavior-to-gene study implicates Pcdh9 in cognitive functions required for long-term social and nonsocial recognition. This role is supported by the involvement of Pcdh9 in sensory cortex development and sensorimotor phenotypes. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Functional neuroimaging of normal aging: Declining brain, adapting brain.

PubMed

Sugiura, Motoaki

2016-09-01

Early functional neuroimaging research on normal aging brain has been dominated by the interest in cognitive decline. In this framework the age-related compensatory recruitment of prefrontal cortex, in terms of executive system or reduced lateralization, has been established. Further details on these compensatory mechanisms and the findings reflecting cognitive decline, however, remain the matter of intensive investigations. Studies in another framework where age-related neural alteration is considered adaptation to the environmental change are recently burgeoning and appear largely categorized into three domains. The age-related increase in activation of the sensorimotor network may reflect the alteration of the peripheral sensorimotor systems. The increased susceptibility of the network for the mental-state inference to the socioemotional significance may be explained by the age-related motivational shift due to the altered social perception. The age-related change in activation of the self-referential network may be relevant to the focused positive self-concept of elderly driven by a similar motivational shift. Across the domains, the concept of the self and internal model may provide the theoretical bases of this adaptation framework. These two frameworks complement each other to provide a comprehensive view of the normal aging brain. Copyright © 2016 Elsevier B.V. All rights reserved.

Chronic Anabolic Androgenic Steroid Exposure Alters Corticotropin Releasing Factor Expression and Anxiety-Like Behaviors in the Female Mouse

PubMed Central

Costine, Beth A; Oberlander, Joseph G; Davis, Matthew C; Penatti, Carlos A A; Porter, Donna M; Leaton, Robert N; Henderson, Leslie P

2010-01-01

Summary In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BNST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST. PMID:20537804

Dose-response characteristics of intravenous ketamine on dissociative stereotypy, locomotion, sensorimotor gating, and nociception in male Sprague-Dawley rats.

PubMed

Radford, Kennett D; Park, Thomas Y; Lee, Bong Hyo; Moran, Sean; Osborne, Lisa A; Choi, Kwang H

2017-02-01

Clinicians administer subanesthetic intravenous (IV) ketamine infusions for treatment of refractory depression, chronic pain, and post-traumatic stress disorder in humans. However, ketamine is administered via the subcutaneous (SC) or intraperitoneal (IP) routes to rodents in most pre-clinical research, which may limit translational application. The present study characterized the dose-response of a subanesthetic IV ketamine bolus (2 and 5mg/kg) and 1-h infusion (5, 10, and 20mg/kg/h) on dissociative stereotypy, locomotion, sensorimotor gating, and thermal nociception in male Sprague-Dawley rats. The secondary aim was to measure ketamine and norketamine plasma concentrations following IV ketamine bolus at 1, 20, and 50min and at the conclusion of the 1-h infusion using liquid chromatography/mass spectrometry. The results showed that ketamine bolus and infusions produced dose-dependent dissociative stereotypy. Bolus (2 and 5mg/kg) and 20mg/kg/h infusion increased locomotor activity while 5mg/kg/h infusion decreased locomotor activity. Both 10 and 20mg/kg/h infusions reduced the acoustic startle reflex, while 5mg/kg bolus and 20mg/kg/h infusion impaired pre-pulse inhibition. Ketamine 5mg/kg bolus and the 10 and 20mg/kg/h infusions induced significant and prolonged antinociception to the hotplate test. Plasma concentrations of ketamine decreased quickly after bolus while norketamine levels increased from 1 to 20min and plateaued from 20 to 50min. The peak ketamine plasma concentrations [ng/ml] were similar between 5mg/kg bolus [4100] vs. 20mg/kg/h infusion [3900], and 2mg/kg bolus [1700] vs. 10mg/kg/h infusion [1500]. These results support the findings from previous ketamine injection studies and further validate the feasibility of administering subanesthetic doses of IV ketamine infusion to rats for neuropharmacological studies. Published by Elsevier Inc.

The α2C-adrenoceptor antagonist, ORM-10921, has antipsychotic-like effects in social isolation reared rats and bolsters the response to haloperidol.

PubMed

Uys, Madeleine; Shahid, Mohammed; Sallinen, Jukka; Dreyer, Walter; Cockeran, Marike; Harvey, Brian H

2016-11-03

Early studies suggest that selective α2C-adrenoceptor (AR)-antagonism has anti-psychotic-like and pro-cognitive properties. However, this has not been demonstrated in an animal model of schizophrenia with a neurodevelopmental construct. The beneficial effects of clozapine in refractory schizophrenia and associated cognitive deficits have, among others, been associated with its α2C-AR modulating activity. Altered brain-derived neurotrophic factor (BDNF) has been linked to schizophrenia and cognitive deficits. We investigated whether the α2C-AR antagonist, ORM-10921, could modulate sensorimotor gating and cognitive deficits, as well as alter striatal BDNF levels in the social isolation reared (SIR) model of schizophrenia, comparing its effects to clozapine and the typical antipsychotic, haloperidol, the latter being devoid of α2C-AR-activity. Moreover, the ability of ORM-10921 to augment the effects of haloperidol on the above parameters was also investigated. Animals received subcutaneous injection of either ORM-10921 (0.01mg/kg), clozapine (5mg/kg), haloperidol (0.2mg/kg), haloperidol (0.2mg/kg)+ORM-10921 (0.01mg/kg) or vehicle once daily for 14days, followed by assessment of novel object recognition (NOR), prepulse inhibition (PPI) of startle response and striatal BDNF levels. SIR significantly attenuated NOR memory as well as PPI, and reduced striatal BDNF levels vs. social controls. Clozapine, ORM-10921 and haloperidol+ORM-10921, but not haloperidol alone, significantly improved SIR-associated deficits in PPI and NOR, with ORM-10921 also significantly improving PPI deficits vs. haloperidol-treated SIR animals. Haloperidol+ORM-10921 significantly reversed reduced striatal BDNF levels in SIR rats. α2C-AR-antagonism improves deficits in cognition and sensorimotor gating in a neurodevelopmental animal model of schizophrenia and bolsters the effects of a typical antipsychotic, supporting a therapeutic role for α2C-AR-antagonism in schizophrenia. Copyright © 2016 Elsevier Inc. All rights reserved.

Reduced Slc1a1 expression is associated with neuroinflammation and impaired sensorimotor gating and cognitive performance in mice: Implications for schizophrenia

PubMed Central

Afshari, Parisa; Yao, Wei-Dong

2017-01-01

We previously reported a 84-Kb hemi-deletion copy number variant at the SLC1A1 gene locus that reduces its expression and appeared causally linked to schizophrenia. In this report, we characterize the in vivo and in vitro consequences of reduced expression of Slc1a1 in mice. Heterozygous (HET) Slc1a1+/- mice, which more closely model the hemi-deletion we found in human subjects, were examined in a series of behavioral, anatomical and biochemical assays. Knockout (KO) mice were also included in the behavioral studies for comparative purposes. Both HET and KO mice exhibited evidence of increased anxiety-like behavior, impaired working memory, decreased exploratory activity and impaired sensorimotor gating, but no changes in overall locomotor activity. The magnitude of changes was approximately equivalent in the HET and KO mice suggesting a dominant effect of the haploinsufficiency. Behavioral changes in the HET mice were accompanied by reduced thickness of the dorsomedial prefrontal cortex. Whole transcriptome RNA-Seq analysis detected expression changes of genes and pathways involved in cytokine signaling and synaptic functions in both brain and blood. Moreover, the brains of Slc1a1+/- mice displayed elevated levels of oxidized glutathione, a trend for increased oxidative DNA damage, and significantly increased levels of cytokines. This latter finding was further supported by SLC1A1 knockdown and overexpression studies in differentiated human neuroblastoma cells, which led to decreased or increased cytokine expression, respectively. Taken together, our results suggest that partial loss of the Slc1a1 gene in mice causes haploinsufficiency associated with behavioral, histological and biochemical changes that reflect an altered redox state and may promote the expression of behavioral features and inflammatory states consistent with those observed in schizophrenia. PMID:28886095

A large single ethnicity study of prepulse inhibition in schizophrenia: Separate analysis by sex focusing on effect of symptoms.

PubMed

Matsuo, Junko; Ota, Miho; Hori, Hiroaki; Hidese, Shinsuke; Teraishi, Toshiya; Ishida, Ikki; Hiraishi, Moeko; Kunugi, Hiroshi

2016-11-01

Deficits in sensorimotor gating, as measured with prepulse inhibition (PPI), have been considered an endophenotype of schizophrenia. However, the question remains whether these deficits are related to current symptoms. This single site study aimed to explore clinical features related to the modulation of startle reflex in a large sample of Japanese patients with schizophrenia (DSM-IV). The subjects comprised 181 patients and 250 healthy controls matched for age and sex. Schizophrenia symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Startle reflex to acoustic stimuli was recorded using a startle stimulus of 115 dB and a prepulse of four different conditions (intensity: 86 dB or 90 dB; lead interval: 60 ms or 120 ms). Patients exhibited significantly reduced startle magnitude (p < 0.001), habituation (p = 0.001), and PPI (90 dB, 60 ms, p = 0.016; 90 dB, 120 ms, p = 0.001) compared with controls. Patients of both sexes exhibited significantly lower habituation and PPI (90 dB, 120 ms) compared with the same sex controls. We could not detect a significant correlation with any clinical variable in the entire patients, however, when men and women were examined separately, there was a negative correlation with the PANSS cognitive domain (ρ = -0.33, p = 0.008) in men, but not in women. Moreover, when patients were subdivided into four clusters, two clusters with high positive symptoms showed significant PPI deficits in men. Our results suggest that sensorimotor gating is impaired in schizophrenia of both sexes, and PPI deficits may be related to thought disturbance and disorganization in male patients with schizophrenia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sensorimotor Gating in Neurotensin-1 Receptor Null Mice

PubMed Central

Feifel, D.; Pang, Z.; Shilling, P.D.; Melendez, G.; Schreiber, R.; Button, D.

2009-01-01

BACKGROUND Converging evidence has implicated endogenous neurotensin (NT) in the pathophysiology of brain processes relevant to schizophrenia. Prepulse inhibition of the startle reflex (PPI) is a measure of sensorimotor gating and considered to be of strong relevance to neuropsychiatric disorders associated with psychosis and cognitive dysfunction. Mice genetically engineered to not express NT display deficits in PPI that model the PPI deficits seen in schizophrenia patients. NT1 receptors have been most strongly implicated in mediating the psychosis relevant effects of NT such as attenuating PPI deficits. To investigate the role of NT1 receptors in the regulation of PPI, we measured baseline PPI in wildtype (WT) and NT1 knockout (KO) mice. We also tested the effects of amphetamine and dizocilpine, a dopamine agonist and NMDA antagonist, respectively, that reduce PPI as well as the NT1 selective receptor agonist, PD149163, known to increase PPI in rats. METHODS Baseline PPI and acoustic startle response were measured in WT and NT1 knockout KO mice. After baseline testing, mice were tested again after receiving intraperatoneal (IP) saline or one of three doses of amphetamine (1.0, 3.0 and 10.0 mg/kg), dizocilpine (0.3, 1.0 and 3.0 mg/kg) and PD149163 (0.5, 2.0 and 6.0 mg/kg) on separate test days. RESULTS Baseline PPI and acoustic startle response in NT1 KO mice were not significantly different from NT1 WT mice. WT and KO mice exhibited similar responses to the PPI-disrupting effects of dizocilpine and amphetamine. PD149163 significantly facilitated PPI (P < 0.004) and decreased the acoustic startle response (P < 0.001) in WT but not NT1 KO mice. CONCLUSIONS The data does not support the regulation of baseline PPI or the PPI disruptive effects of amphetamine or dizocilpine by endogenous NT acting at the NT1 receptor, although they support the antipsychotic potential of pharmacological activation of NT1 receptors by NT1 agonists. PMID:19596359

Comparison of respiratory-gated and respiratory-ungated planning in scattered carbon ion beam treatment of the pancreas using four-dimensional computed tomography.

PubMed

Mori, Shinichiro; Yanagi, Takeshi; Hara, Ryusuke; Sharp, Gregory C; Asakura, Hiroshi; Kumagai, Motoki; Kishimoto, Riwa; Yamada, Shigeru; Kato, Hirotoshi; Kandatsu, Susumu; Kamada, Tadashi

2010-01-01

We compared respiratory-gated and respiratory-ungated treatment strategies using four-dimensional (4D) scattered carbon ion beam distribution in pancreatic 4D computed tomography (CT) datasets. Seven inpatients with pancreatic tumors underwent 4DCT scanning under free-breathing conditions using a rapidly rotating cone-beam CT, which was integrated with a 256-slice detector, in cine mode. Two types of bolus for gated and ungated treatment were designed to cover the planning target volume (PTV) using 4DCT datasets in a 30% duty cycle around exhalation and a single respiratory cycle, respectively. Carbon ion beam distribution for each strategy was calculated as a function of respiratory phase by applying the compensating bolus to 4DCT at the respective phases. Smearing was not applied to the bolus, but consideration was given to drill diameter. The accumulated dose distributions were calculated by applying deformable registration and calculating the dose-volume histogram. Doses to normal tissues in gated treatment were minimized mainly on the inferior aspect, which thereby minimized excessive doses to normal tissues. Over 95% of the dose, however, was delivered to the clinical target volume at all phases for both treatment strategies. Maximum doses to the duodenum and pancreas averaged across all patients were 43.1/43.1 GyE (ungated/gated) and 43.2/43.2 GyE (ungated/gated), respectively. Although gated treatment minimized excessive dosing to normal tissue, the difference between treatment strategies was small. Respiratory gating may not always be required in pancreatic treatment as long as dose distribution is assessed. Any application of our results to clinical use should be undertaken only after discussion with oncologists, particularly with regard to radiotherapy combined with chemotherapy.

Sleep extension normalizes ERP of waking auditory sensory gating in healthy habitually short sleeping individuals.

PubMed

Gumenyuk, Valentina; Korzyukov, Oleg; Roth, Thomas; Bowyer, Susan M; Drake, Christopher L

2013-01-01

Chronic sleep loss has been associated with increased daytime sleepiness, as well as impairments in memory and attentional processes. In the present study, we evaluated the neuronal changes of a pre-attentive process of wake auditory sensory gating, measured by brain event-related potential (ERP)--P50 in eight normal sleepers (NS) (habitual total sleep time (TST) 7 h 32 m) vs. eight chronic short sleeping individuals (SS) (habitual TST ≤6 h). To evaluate the effect of sleep extension on sensory gating, the extended sleep condition was performed in chronic short sleeping individuals. Thus, one week of time in bed (6 h 11 m) corresponding to habitual short sleep (hSS), and one week of extended time (∼ 8 h 25 m) in bed corresponding to extended sleep (eSS), were counterbalanced in the SS group. The gating ERP assessment was performed on the last day after each sleep condition week (normal sleep and habitual short and extended sleep), and was separated by one week with habitual total sleep time and monitored by a sleep diary. We found that amplitude of gating was lower in SS group compared to that in NS group (0.3 µV vs. 1.2 µV, at Cz electrode respectively). The results of the group × laterality interaction showed that the reduction of gating amplitude in the SS group was due to lower amplitude over the left hemisphere and central-midline sites relative to that in the NS group. After sleep extension the amplitude of gating increased in chronic short sleeping individuals relative to their habitual short sleep condition. The sleep condition × frontality interaction analysis confirmed that sleep extension significantly increased the amplitude of gating over frontal and central brain areas compared to parietal brain areas.

Normobaric hyperoxia markedly reduces brain damage and sensorimotor deficits following brief focal ischaemia.

PubMed

Ejaz, Sohail; Emmrich, Julius V; Sitnikov, Sergey L; Hong, Young T; Sawiak, Stephen J; Fryer, Tim D; Aigbirhio, Franklin I; Williamson, David J; Baron, Jean-Claude

2016-03-01

'True' transient ischaemic attacks are characterized not only clinically, but also radiologically by a lack of corresponding changes on magnetic resonance imaging. During a transient ischaemic attack it is assumed that the affected tissue is penumbral but rescued by early spontaneous reperfusion. There is, however, evidence from rodent studies that even brief focal ischaemia not resulting in tissue infarction can cause extensive selective neuronal loss associated with long-lasting sensorimotor impairment but normal magnetic resonance imaging. Selective neuronal loss might therefore contribute to the increasingly recognized cognitive impairment occurring in patients with transient ischaemic attacks. It is therefore relevant to consider treatments to reduce brain damage occurring with transient ischaemic attacks. As penumbral neurons are threatened by markedly constrained oxygen delivery, improving the latter by increasing arterial O2 content would seem logical. Despite only small increases in arterial O2 content, normobaric oxygen therapy experimentally induces significant increases in penumbral O2 pressure and by such may maintain the penumbra alive until reperfusion. Nevertheless, the effects of normobaric oxygen therapy on infarct volume in rodent models have been conflicting, although duration of occlusion appeared an important factor. Likewise, in the single randomized trial published to date, early-administered normobaric oxygen therapy had no significant effect on clinical outcome despite reduced diffusion-weighted imaging lesion growth during therapy. Here we tested the hypothesis that normobaric oxygen therapy prevents both selective neuronal loss and sensorimotor deficits in a rodent model mimicking true transient ischaemic attack. Normobaric oxygen therapy was applied from the onset and until completion of 15 min distal middle cerebral artery occlusion in spontaneously hypertensive rats, a strain representative of the transient ischaemic attack-prone population. Whereas normoxic controls showed normal magnetic resonance imaging but extensive cortical selective neuronal loss associated with microglial activation (present both at Day 14 in vivo and at Day 28 post-mortem) and marked and long-lasting sensorimotor deficits, normobaric oxygen therapy completely prevented sensorimotor deficit (P < 0.02) and near-completely Day 28 selective neuronal loss (P < 0.005). Microglial activation was substantially reduced at Day 14 and completely prevented at Day 28 (P = 0.002). Our findings document that normobaric oxygen therapy administered during ischaemia nearly completely prevents the neuronal death, microglial inflammation and sensorimotor impairment that characterize this rodent true transient ischaemic attack model. Taken together with the available literature, normobaric oxygen therapy appears a promising therapy for short-lasting ischaemia, and is attractive clinically as it could be started at home in at-risk patients or in the ambulance in subjects suspected of transient ischaemic attack/early stroke. It may also be a straightforward adjunct to reperfusion therapies, and help prevent subtle brain damage potentially contributing to long-term cognitive and sensorimotor impairment in at-risk populations. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

EEG Mu (µ) rhythm spectra and oscillatory activity differentiate stuttering from non-stuttering adults.

PubMed

Saltuklaroglu, Tim; Harkrider, Ashley W; Thornton, David; Jenson, David; Kittilstved, Tiffani

2017-06-01

Stuttering is linked to sensorimotor deficits related to internal modeling mechanisms. This study compared spectral power and oscillatory activity of EEG mu (μ) rhythms between persons who stutter (PWS) and controls in listening and auditory discrimination tasks. EEG data were analyzed from passive listening in noise and accurate (same/different) discrimination of tones or syllables in quiet and noisy backgrounds. Independent component analysis identified left and/or right μ rhythms with characteristic alpha (α) and beta (β) peaks localized to premotor/motor regions in 23 of 27 people who stutter (PWS) and 24 of 27 controls. PWS produced μ spectra with reduced β amplitudes across conditions, suggesting reduced forward modeling capacity. Group time-frequency differences were associated with noisy conditions only. PWS showed increased μ-β desynchronization when listening to noise and early in discrimination events, suggesting evidence of heightened motor activity that might be related to forward modeling deficits. PWS also showed reduced μ-α synchronization in discrimination conditions, indicating reduced sensory gating. Together these findings indicate spectral and oscillatory analyses of μ rhythms are sensitive to stuttering. More specifically, they can reveal stuttering-related sensorimotor processing differences in listening and auditory discrimination that also may be influenced by basal ganglia deficits. Copyright © 2017 Elsevier Inc. All rights reserved.

Chronic and acute intranasal oxytocin produce divergent social effects in mice.

PubMed

Huang, Huiping; Michetti, Caterina; Busnelli, Marta; Managò, Francesca; Sannino, Sara; Scheggia, Diego; Giancardo, Luca; Sona, Diego; Murino, Vittorio; Chini, Bice; Scattoni, Maria Luisa; Papaleo, Francesco

2014-04-01

Intranasal administration of oxytocin (OXT) might be a promising new adjunctive therapy for mental disorders characterized by social behavioral alterations such as autism and schizophrenia. Despite promising initial studies in humans, it is not yet clear the specificity of the behavioral effects induced by chronic intranasal OXT and if chronic intranasal OXT could have different effects compared with single administration. This is critical for the aforementioned chronic mental disorders that might potentially involve life-long treatments. As a first step to address these issues, here we report that chronic intranasal OXT treatment in wild-type C57BL/6J adult mice produced a selective reduction of social behaviors concomitant to a reduction of the OXT receptors throughout the brain. Conversely, acute intranasal OXT treatment produced partial increases in social behaviors towards opposite-sex novel-stimulus female mice, while on the other hand, it decreased social exploration of same-sex novel stimulus male mice, without affecting social behavior towards familiar stimulus male mice. Finally, prolonged exposure to intranasal OXT treatments did not alter, in wild-type animals, parameters of general health such as body weight, locomotor activity, olfactory and auditory functions, nor parameters of memory and sensorimotor gating abilities. These results indicate that a prolonged over-stimulation of a 'healthy' oxytocinergic brain system, with no inherent deficits in social interaction and normal endogenous levels of OXT, results in specific detrimental effects in social behaviors.

Impact of Virtual Environments on Sensorimotor Coordination and User Safety

NASA Technical Reports Server (NTRS)

Harm, Deborah L.; Taylor, Laura C.; Kennedy, Robert S.; Reschke, Millard F.

2011-01-01

One critical unresolved issue related to the safe use of virtual environments (VEs) is maladaptive sensorimotor coordination following exposure to VEs. Moving visual displays used in VEs, especially in the absence of concordant vestibular signals leads to adaptive responses during VE exposure, but maladaptive responses following return to the normal environment. In the current set of investigations, we examined the effect of HMD and dome VE displays on eye-head-hand coordination, gaze holding and postural equilibrium. Subjects (61) performed a navigation and a pick and place task. Further, we compared 30 min and 60 min exposures across 3 days (each separated by 1 day). A subset of these results will be presented. In general, we found significant decrements in all three measures following exposure to the VEs. In addition, we found that these disturbances generally recovered within 1-2 hrs and decreased across days. These findings suggest the need for post-VE monitoring of sensorimotor coordination and for developing a set of recommendations for users concerning activities that are safe to engage in following use of a VE.

Lifespan development of attentiveness in domestic dogs: drawing parallels with humans

PubMed Central

Wallis, Lisa J.; Range, Friederike; Müller, Corsin A.; Serisier, Samuel; Huber, Ludwig; Zsó, Virányi

2014-01-01

Attention is pivotal to consciousness, perception, cognition, and working memory in all mammals, and therefore changes in attention over the lifespan are likely to influence development and aging of all of these functions. Due to their evolutionary and developmental history, the dog is being recognized as an important species for modeling human healthspan, aging and associated diseases. In this study, we investigated the normal lifespan development of attentiveness of pet dogs in naturalistic situations, and compared the resulting cross-sectional developmental trajectories with data from previous studies in humans. We tested a sample of 145 Border collies (6 months to 14 years) with humans and objects or food as attention attractors, in order to assess their attentional capture, sustained and selective attention, and sensorimotor abilities. Our results reveal differences in task relevance in sustained attentional performance when watching a human or a moving object, which may be explained by life-long learning processes involving such stimuli. During task switching we found that dogs’ selective attention and sensorimotor abilities showed differences between age groups, with performance peaking at middle age. Dogs’ sensorimotor abilities showed a quadratic distribution with age and were correlated with selective attention performance. Our results support the hypothesis that the development and senescence of sensorimotor and attentional control may be fundamentally interrelated. Additionally, attentional capture, sustained attention, and sensorimotor control developmental trajectories paralleled those found in humans. Given that the development of attention is similar across humans and dogs, we propose that the same regulatory mechanisms are likely to be present in both species. Finally, this cross-sectional study provides the first description of age group changes in attention over the lifespan of pet dogs. PMID:24570668

Use of Virtual Reality for Space Flight

NASA Technical Reports Server (NTRS)

Harm, Deborah; Taylor, L. C.; Reschke, M. F.

2011-01-01

Virtual environments offer unique training opportunities, particularly for training astronauts and preadapting them to the novel sensory conditions of microgravity. Two unresolved human factors issues in virtual reality (VR) systems are: 1) potential "cybersickness", and 2) maladaptive sensorimotor performance following exposure to VR systems. Interestingly, these aftereffects are often quite similar to adaptive sensorimotor responses observed in astronauts during and/or following space flight. Active exploratory behavior in a new environment, with resulting feedback and the formation of new associations between sensory inputs and response outputs, promotes appropriate perception and motor control in the new environment. Thus, people adapt to consistent, sustained alterations of sensory input such as those produced by microgravity. Our research examining the effects of repeated exposures to a full field of view dome VR system showed that motion sickness and initial decrements in eye movement and postural control were greatly diminished following three exposures. These results suggest that repeated transitions between VR and the normal environment preflight might be a useful countermeasure for neurosensory and sensorimotor effects of space flight. The range of VR applications is enormous, extending from ground-based VR training for extravehicular activities at NASA, to medical and educational uses. It seems reasonable to suggest that other space related uses of VR should be investigated. For example, 1) use of head-mounted VR on orbit to rehearse/practice upcoming operational activities, and 2) ground-based VR training for emergency egress procedures. We propose that by combining VR designed for operational activities preflight, along with an appropriate schedule to facilitate sensorimotor adaptation and improve spatial orientation would potentially accomplish two important goals for astronauts and cosmonauts, preflight sensorimotor adaption and enhanced operational training at the same time. Such efforts could support both improved health and performance on orbit and improved operational training in the most efficient manner.

Investigation of gene effects and epistatic interactions between Akt1 and neuregulin 1 in the regulation of behavioral phenotypes and social functions in genetic mouse models of schizophrenia

PubMed Central

Huang, Ching-Hsun; Pei, Ju-Chun; Luo, Da-Zhong; Chen, Ching; Chen, Yi-Wen; Lai, Wen-Sung

2015-01-01

Accumulating evidence from human genetic studies has suggested several functional candidate genes that might contribute to susceptibility to schizophrenia, including AKT1 and neuregulin 1 (NRG1). Recent findings also revealed that NRG1 stimulates the PI3-kinase/AKT signaling pathway, which might be involved in the functional outcomes of some schizophrenic patients. The aim of this study was to evaluate the effect of Akt1-deficiency and Nrg1-deficiency alone or in combination in the regulation of behavioral phenotypes, cognition, and social functions using genetically modified mice as a model. Male Akt1+/−, Nrg1+/−, and double mutant mice were bred and compared with their wild-type (WT) littermate controls. In Experiment 1, general physical examination revealed that all mutant mice displayed a normal profile of body weight during development and a normal brain activity with microPET scan. In Experiment 2, no significant genotypic differences were found in our basic behavioral phenotyping, including locomotion, anxiety-like behavior, and sensorimotor gating function. However, both Nrg1+/− and double mutant mice exhibited impaired episodic-like memory. Double mutant mice also had impaired sociability. In Experiment 3, a synergistic epistasis between Akt1 and Nrg1 was further confirmed in double mutant mice in that they had impaired social interaction compared to the other 3 groups, especially encountering with a novel male or an ovariectomized female. Double mutant and Nrg1+/− mice also emitted fewer female urine-induced ultrasonic vocalization calls. Collectively, our results indicate that double deficiency of Akt1 and Nrg1 can result in the impairment of social cognitive functions, which might be pertinent to the pathogenesis of schizophrenia-related social cognition. PMID:25688191

Investigation of gene effects and epistatic interactions between Akt1 and neuregulin 1 in the regulation of behavioral phenotypes and social functions in genetic mouse models of schizophrenia.

PubMed

Huang, Ching-Hsun; Pei, Ju-Chun; Luo, Da-Zhong; Chen, Ching; Chen, Yi-Wen; Lai, Wen-Sung

2014-01-01

Accumulating evidence from human genetic studies has suggested several functional candidate genes that might contribute to susceptibility to schizophrenia, including AKT1 and neuregulin 1 (NRG1). Recent findings also revealed that NRG1 stimulates the PI3-kinase/AKT signaling pathway, which might be involved in the functional outcomes of some schizophrenic patients. The aim of this study was to evaluate the effect of Akt1-deficiency and Nrg1-deficiency alone or in combination in the regulation of behavioral phenotypes, cognition, and social functions using genetically modified mice as a model. Male Akt1 (+/-), Nrg1 (+/-), and double mutant mice were bred and compared with their wild-type (WT) littermate controls. In Experiment 1, general physical examination revealed that all mutant mice displayed a normal profile of body weight during development and a normal brain activity with microPET scan. In Experiment 2, no significant genotypic differences were found in our basic behavioral phenotyping, including locomotion, anxiety-like behavior, and sensorimotor gating function. However, both Nrg1 (+/-) and double mutant mice exhibited impaired episodic-like memory. Double mutant mice also had impaired sociability. In Experiment 3, a synergistic epistasis between Akt1 and Nrg1 was further confirmed in double mutant mice in that they had impaired social interaction compared to the other 3 groups, especially encountering with a novel male or an ovariectomized female. Double mutant and Nrg1 (+/-) mice also emitted fewer female urine-induced ultrasonic vocalization calls. Collectively, our results indicate that double deficiency of Akt1 and Nrg1 can result in the impairment of social cognitive functions, which might be pertinent to the pathogenesis of schizophrenia-related social cognition.

Assessment of Glutamate Transporter GLAST (EAAT1)-Deficient Mice for Phenotypes Relevant to the Negative and Executive/Cognitive Symptoms of Schizophrenia

PubMed Central

Karlsson, Rose-Marie; Tanaka, Kohichi; Saksida, Lisa M; Bussey, Timothy J; Heilig, Markus; Holmes, Andrew

2012-01-01

Glutamatergic dysfunction is increasingly implicated in the pathophysiology of schizophrenia. Current models postulate that dysfunction of glutamate and its receptors underlie many of the symptoms in this disease. However, the mechanisms involved are not well understood. Although elucidating the role for glutamate transporters in the disease has been limited by the absence of pharmacological tools that selectively target the transporter, we recently showed that glial glutamate and aspartate transporter (GLAST; excitatory amino-acid transporter 1) mutant mice exhibit abnormalities on behavioral measures thought to model the positive symptoms of schizophrenia, some of which were rescued by treatment with either haloperidol or the mGlu2/3 agonist, LY379268 the mGlu2/3 agonist, LY379268. To further determine the role of GLAST in schizophrenia-related behaviors we tested GLAST mutant mice on a series of behavioral paradigms associated with the negative (social withdrawal, anhedonia), sensorimotor gating (prepulse inhibition of startle), and executive/cognitive (discrimination learning, extinction) symptoms of schizophrenia. GLAST knockout (KO) mice showed poor nesting behavior and abnormal sociability, whereas KO and heterozygous (HET) both demonstrated lesser preference for a novel social stimulus compared to wild-type littermate controls. GLAST KO, but not HET, had a significantly reduced acoustic startle response, but no significant deficit in prepulse inhibition of startle. GLAST KO and HET showed normal sucrose preference. In an instrumental visual discrimination task, KO showed impaired learning. By contrast, acquisition and extinction of a simple instrumental response was normal. The mGlu2/3 agonist, LY379268, failed to rescue the discrimination impairment in KO mice. These findings demonstrate that gene deletion of GLAST produces select phenotypic abnormalities related to the negative and cognitive symptoms of schizophrenia. PMID:19078949

Evaluation of segmental left ventricular wall motion by equilibrium gated radionuclide ventriculography.

PubMed

Van Nostrand, D; Janowitz, W R; Holmes, D R; Cohen, H A

1979-01-01

The ability of equilibrium gated radionuclide ventriculography to detect segmental left ventricular (LV) wall motion abnormalities was determined in 26 patients undergoing cardiac catheterization. Multiple gated studies obtained in 30 degrees right anterior oblique and 45 degrees left anterior oblique projections, played back in a movie format, were compared to the corresponding LV ventriculograms. The LV wall in the two projections was divided into eight segments. Each segment was graded as normal, hypokinetic, akinetic, dyskinetic, or indeterminate. Thirteen percent of the segments in the gated images were indeterminate; 24 out of 27 of these were proximal or distal inferior wall segments. There was exact agreement in 86% of the remaining segments. The sensitivity of the radionuclide technique for detecting normal versus any abnormal wall motion was 71%, with a specificity of 99%. Equilibrium gated ventriculography is an excellent noninvasive technique for evaluating segmental LV wall motion. It is least reliable in assessing the proximal inferior wall and interventricular septum.

Investigation of gate-diode degradation in normally-off p-GaN/AlGaN/GaN high-electron-mobility transistors

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

Ťapajna, M., E-mail: milan.tapajna@savba.sk; Kuzmík, J.; Hilt, O.

2015-11-09

Gate diode conduction mechanisms were analyzed in normally-off p-GaN/AlGaN/GaN high-electron mobility transistors grown on Si wafers before and after forward bias stresses. Electrical characterization of the gate diodes indicates forward current to be limited by channel electrons injected through the AlGaN/p-GaN triangular barrier promoted by traps. On the other hand, reverse current was found to be consistent with carrier generation-recombination processes in the AlGaN layer. Soft breakdown observed after ∼10{sup 5 }s during forward bias stress at gate voltage of 7 V was attributed to formation of conductive channel in p-GaN/AlGaN gate stack via trap generation and percolation mechanism, likely due tomore » coexistence of high electric field and high forward current density. Possible enhancement of localized conductive channels originating from spatial inhomogeneities is proposed to be responsible for the degradation.« less

Using in-process measurements of open-gate structures to evaluate threshold voltage of normally-off GaN-based high electron mobility transistors

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

Hou, Bin; Ma, Xiao-Hua, E-mail: xhma@xidian.edu.cn, E-mail: yhao@xidian.edu.cn; Chen, Wei-Wei

The parameters of open-gate structures treated with different etching time were monitored during the gate recess process, and their impacts on the threshold voltage (V{sub th}) of final fabricated AlGaN/GaN high electron mobility transistors (HEMTs) based on open-gate structures were discussed in this paper. It is found that V{sub th} can exceed 0 V when channel resistance in the recessed region (R{sub on-open}) increases over ∼275 Ω mm, maximum current (I{sub Dmax}) decreases below ∼29 mA/mm, or recessed barrier thickness (t{sub RB}) is below ∼7.5 nm. In addition, t{sub RB} obtained by atomic force microscopy measurements and C-V measurements are also compared. Finally,more » theoretical common criteria based on the experimental results of this work for t{sub RB} and R{sub on-open} were established to evaluate the V{sub th} of a regular normally-off AlGaN/GaN HEMTs. The results indicate that these parameters of open-gate structure can be utilized to achieve normally-off HEMTs with controllable V{sub th}.« less

SU-F-T-634: Feasibility Study of Respiratory Gated RapidArc SBRT Using a 6MV FFF Photon Beam

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

Dou, K; Safaraz, M; Rodgers, J

Purpose: To conduct a feasibility study on retrospective respiratory gating and marker tracking for lung stereotactic body radiotherapy (SBRT) with a gated RapidArc delivery using a 6MV flattened filter free photon mode. Methods: A CIRS dynamic thorax phantom Model 008A with different inserts was used for treatment planning and respiratory gating. 4D CT had a free breathing simulation followed by a respiration gated, ten phased CT using a Philips Brilliance CT with a Varian RPM respiratory gating system. The internal target volume was created from the ten phase gated CT images, followed by exporting to a Varian Eclipse TPS v11more » for treatment planning on the free breath images. Both MIP and AIP were also generated for comparison of planning and target motion tracking. The planned dose was delivered with a 6MV FFF photon beam from a Varian TrueBeam accelerator. Gated target motion was also verified by tracking the implanted makers during delivery using continuous kV imaging in addition to CBCT, kV and MV localization and verification. Results: Gating was studied in three situations of lower, normal, and faster breathing at a respiratory cycle of 5, 15 and 25 breaths per minute, respectively. 4D treatment planning was performed at a normal breathing of 15 breaths per minute. The gated patterns obtained using the TrueBeam IR camera were compared with the planned ones while gating operation was added prior to delivery . Gating was realized only when the measured respiratory patterns matched to the planned ones. The gated target motion was verified within the tolerance by kV and MV imaging. Either free breathing CT or averaged CT images were studied to be good for image guidance to align the target. Conclusion: Gated RapidArc SBRT delivered with a 6MV FFF photon beam is realized using a dynamic lung phantom.« less

Valve

DOEpatents

Cho, Nakwon

1980-01-01

A positive acting valve suitable for operation in a corrosive environment is provided. The valve includes a hollow valve body defining an open-ended bore for receiving two, axially aligned, spaced-apart, cylindrical inserts. One insert, designated the seat insert, terminates inside the valve body in an annular face which lies within plane normal to the axis of the two inserts. An elastomeric O-ring seal is disposed in a groove extending about the annular face. The other insert, designated the wedge insert, terminates inside the valve body in at least two surfaces oppositely inclined with respect to each other and with respect to a plane normal to the axis of the two inserts. An elongated reciprocable gate, movable between the two inserts along a path normal to the axis of the two inserts, has a first flat face portion disposed adjacent and parallel to the annular face of the seat insert. The gate has a second face portion opposite to the first face portion provided with at least two oppositely inclined surfaces for mating with respective inclined surfaces of the wedge insert. An opening is provided through the gate which registers with a flow passage through the two inserts when the valve is open. Interaction of the respective inclined surfaces of the gate and wedge insert act to force the first flat face portion of the gate against the O-ring seal in the seat insert at the limits of gate displacement where it reaches its respective fully open and fully closed positions.

Drain current enhancement induced by hole injection from gate of 600-V-class normally off gate injection transistor under high temperature conditions up to 200 °C

NASA Astrophysics Data System (ADS)

Ishii, Hajime; Ueno, Hiroaki; Ueda, Tetsuzo; Endoh, Tetsuo

2018-06-01

In this paper, the current–voltage (I–V) characteristics of a 600-V-class normally off GaN gate injection transistor (GIT) from 25 to 200 °C are analyzed, and it is revealed that the drain current of the GIT increases during high-temperature operation. It is found that the maximum drain current (I dmax) of the GIT is 86% higher than that of a conventional 600-V-class normally off GaN metal insulator semiconductor hetero-FET (MIS-HFET) at 150 °C, whereas the GIT obtains 56% I dmax even at 200 °C. Moreover, the mechanism of the drain current increase of the GIT is clarified by examining the relationship between the temperature dependence of the I–V characteristics of the GIT and the gate hole injection effect determined from the shift of the second transconductance (g m) peak of the g m–V g characteristic. From the above, the GIT is a promising device with enough drivability for future power switching applications even under high-temperature conditions.

Sliding-gate valve for use with abrasive materials

DOEpatents

Ayers, Jr., William J.; Carter, Charles R.; Griffith, Richard A.; Loomis, Richard B.; Notestein, John E.

1985-01-01

The invention is a flow and pressure-sealing valve for use with abrasive solids. The valve embodies special features which provide for long, reliable operating lifetimes in solids-handling service. The valve includes upper and lower transversely slidable gates, contained in separate chambers. The upper gate provides a solids-flow control function, whereas the lower gate provides a pressure-sealing function. The lower gate is supported by means for (a) lifting that gate into sealing engagement with its seat when the gate is in its open and closed positions and (b) lowering the gate out of contact with its seat to permit abrasion-free transit of the gate between its open and closed positions. When closed, the upper gate isolates the lower gate from the solids. Because of this shielding action, the sealing surface of the lower gate is not exposed to solids during transit or when it is being lifted or lowered. The chamber containing the lower gate normally is pressurized slightly, and a sweep gas is directed inwardly across the lower-gate sealing surface during the vertical translation of the gate.

Quantifying the impact of respiratory-gated 4D CT acquisition on thoracic image quality: a digital phantom study.

PubMed

Bernatowicz, K; Keall, P; Mishra, P; Knopf, A; Lomax, A; Kipritidis, J

2015-01-01

Prospective respiratory-gated 4D CT has been shown to reduce tumor image artifacts by up to 50% compared to conventional 4D CT. However, to date no studies have quantified the impact of gated 4D CT on normal lung tissue imaging, which is important in performing dose calculations based on accurate estimates of lung volume and structure. To determine the impact of gated 4D CT on thoracic image quality, the authors developed a novel simulation framework incorporating a realistic deformable digital phantom driven by patient tumor motion patterns. Based on this framework, the authors test the hypothesis that respiratory-gated 4D CT can significantly reduce lung imaging artifacts. Our simulation framework synchronizes the 4D extended cardiac torso (XCAT) phantom with tumor motion data in a quasi real-time fashion, allowing simulation of three 4D CT acquisition modes featuring different levels of respiratory feedback: (i) "conventional" 4D CT that uses a constant imaging and couch-shift frequency, (ii) "beam paused" 4D CT that interrupts imaging to avoid oversampling at a given couch position and respiratory phase, and (iii) "respiratory-gated" 4D CT that triggers acquisition only when the respiratory motion fulfills phase-specific displacement gating windows based on prescan breathing data. Our framework generates a set of ground truth comparators, representing the average XCAT anatomy during beam-on for each of ten respiratory phase bins. Based on this framework, the authors simulated conventional, beam-paused, and respiratory-gated 4D CT images using tumor motion patterns from seven lung cancer patients across 13 treatment fractions, with a simulated 5.5 cm(3) spherical lesion. Normal lung tissue image quality was quantified by comparing simulated and ground truth images in terms of overall mean square error (MSE) intensity difference, threshold-based lung volume error, and fractional false positive/false negative rates. Averaged across all simulations and phase bins, respiratory-gating reduced overall thoracic MSE by 46% compared to conventional 4D CT (p ∼ 10(-19)). Gating leads to small but significant (p < 0.02) reductions in lung volume errors (1.8%-1.4%), false positives (4.0%-2.6%), and false negatives (2.7%-1.3%). These percentage reductions correspond to gating reducing image artifacts by 24-90 cm(3) of lung tissue. Similar to earlier studies, gating reduced patient image dose by up to 22%, but with scan time increased by up to 135%. Beam paused 4D CT did not significantly impact normal lung tissue image quality, but did yield similar dose reductions as for respiratory-gating, without the added cost in scanning time. For a typical 6 L lung, respiratory-gated 4D CT can reduce image artifacts affecting up to 90 cm(3) of normal lung tissue compared to conventional acquisition. This image improvement could have important implications for dose calculations based on 4D CT. Where image quality is less critical, beam paused 4D CT is a simple strategy to reduce imaging dose without sacrificing acquisition time.

Increases in both cerebral glucose utilization and blood flow during execution of a somatosensory task.

PubMed

Ginsberg, M D; Chang, J Y; Kelley, R E; Yoshii, F; Barker, W W; Ingenito, G; Boothe, T E

1988-02-01

To investigate local metabolic and hemodynamic interrelationships during functional activation of the brain, paired studies of local cerebral glucose utilization (lCMRGlc) and blood flow (lCBF) were carried out in 10 normal subjects (9 right-handed, 1 ambidextrous) at rest and during a unilateral discriminative somatosensory/motor task--palpation and sorting of mah-jongg tiles by engraved design. The extent of activation was assessed on the basis of percentage difference images following normalization to compensate for global shifts. The somatosensory stimulus elevated lCMRGlc by 16.9 +/- 3.5% (mean +/- standard deviation) and lCBF by 26.5 +/- 5.1% in the contralateral sensorimotor cortical focus; smaller increments were noted in the homologous ipsilateral site. The increments of lCMRGlc and lCBF correlated poorly with one another in individual subjects. Stimulation of the right hand resulted in significantly higher contralateral lCMRGlc activation (19.6%) than did stimulation of the left hand (14.1%) (p less than 0.005), whereas the lCBF response was independent of the hand stimulated. Our results indicate that both glycolytic metabolism and blood flow increase locally with the execution of an active sensorimotor task and suggest that both measures may serve as reliable markers of functional activation of the normal brain.

Counting on the mental number line to make a move: sensorimotor ('pen') control and numerical processing.

PubMed

Sheridan, Rebecca; van Rooijen, Maaike; Giles, Oscar; Mushtaq, Faisal; Steenbergen, Bert; Mon-Williams, Mark; Waterman, Amanda

2017-10-01

Mathematics is often conducted with a writing implement. But is there a relationship between numerical processing and sensorimotor 'pen' control? We asked participants to move a stylus so it crossed an unmarked line at a location specified by a symbolic number (1-9), where number colour indicated whether the line ran left-right ('normal') or vice versa ('reversed'). The task could be simplified through the use of a 'mental number line' (MNL). Many modern societies use number lines in mathematical education and the brain's representation of number appears to follow a culturally determined spatial organisation (so better task performance is associated with this culturally normal orientation-the MNL effect). Participants (counter-balanced) completed two consistent blocks of trials, 'normal' and 'reversed', followed by a mixed block where line direction varied randomly. Experiment 1 established that the MNL effect was robust, and showed that the cognitive load associated with reversing the MNL not only affected response selection but also the actual movement execution (indexed by duration) within the mixed trials. Experiment 2 showed that an individual's motor abilities predicted performance in the difficult (mixed) condition but not the easier blocks. These results suggest that numerical processing is not isolated from motor capabilities-a finding with applied consequences.

Tool-Use and the Left Hemisphere: What Is Lost in Ideomotor Apraxia?

ERIC Educational Resources Information Center

Sunderland, Alan; Wilkins, Leigh; Dineen, Rob; Dawson, Sophie E.

2013-01-01

Impaired tool related action in ideomotor apraxia is normally ascribed to loss of sensorimotor memories for habitual actions (engrams), but this account has not been tested against a hypothesis of a general deficit in representation of hand-object spatial relationships. Rapid reaching for familiar tools was compared with reaching for abstract…

Initial Sensorimotor and Cardiovascular Data Acquired from Soyuz Landings: Establishing a Functional Performance Recovery Time Constant

NASA Technical Reports Server (NTRS)

Reschke, M. F.; Kozlovskaya, I. B.; Kofman, I. S.; Tomilovskaya, E. S.; Cerisano, J. M.; Bloomberg, J. J.; Stenger, M. B.; Platts, S. H.; Rukavishnikov, I. V.; Fomina, E. V.;

Comparison of Respiratory-Gated and Respiratory-Ungated Planning in Scattered Carbon Ion Beam Treatment of the Pancreas Using Four-Dimensional Computed Tomography

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

Mori, Shinichiro, E-mail: shinshin@nirs.go.j; Yanagi, Takeshi; Hara, Ryusuke

2010-01-15

Purpose: We compared respiratory-gated and respiratory-ungated treatment strategies using four-dimensional (4D) scattered carbon ion beam distribution in pancreatic 4D computed tomography (CT) datasets. Methods and Materials: Seven inpatients with pancreatic tumors underwent 4DCT scanning under free-breathing conditions using a rapidly rotating cone-beam CT, which was integrated with a 256-slice detector, in cine mode. Two types of bolus for gated and ungated treatment were designed to cover the planning target volume (PTV) using 4DCT datasets in a 30% duty cycle around exhalation and a single respiratory cycle, respectively. Carbon ion beam distribution for each strategy was calculated as a function ofmore » respiratory phase by applying the compensating bolus to 4DCT at the respective phases. Smearing was not applied to the bolus, but consideration was given to drill diameter. The accumulated dose distributions were calculated by applying deformable registration and calculating the dose-volume histogram. Results: Doses to normal tissues in gated treatment were minimized mainly on the inferior aspect, which thereby minimized excessive doses to normal tissues. Over 95% of the dose, however, was delivered to the clinical target volume at all phases for both treatment strategies. Maximum doses to the duodenum and pancreas averaged across all patients were 43.1/43.1 GyE (ungated/gated) and 43.2/43.2 GyE (ungated/gated), respectively. Conclusions: Although gated treatment minimized excessive dosing to normal tissue, the difference between treatment strategies was small. Respiratory gating may not always be required in pancreatic treatment as long as dose distribution is assessed. Any application of our results to clinical use should be undertaken only after discussion with oncologists, particularly with regard to radiotherapy combined with chemotherapy.« less

Factors affecting speech understanding in gated interference: Cochlear implant users and normal-hearing listeners

NASA Astrophysics Data System (ADS)

Nelson, Peggy B.; Jin, Su-Hyun

2004-05-01

Previous work [Nelson, Jin, Carney, and Nelson (2003), J. Acoust. Soc. Am 113, 961-968] suggested that cochlear implant users do not benefit from masking release when listening in modulated noise. The previous findings indicated that implant users experience little to no release from masking when identifying sentences in speech-shaped noise, regardless of the modulation frequency applied to the noise. The lack of masking release occurred for all implant subjects who were using three different devices and speech processing strategies. In the present study, possible causes of this reduced masking release in implant listeners were investigated. Normal-hearing listeners, implant users, and normal-hearing listeners presented with a four-band simulation of a cochlear implant were tested for their understanding of sentences in gated noise (1-32 Hz gate frequencies) when the duty cycle of the noise was varied from 25% to 75%. No systematic effect of noise duty cycle on implant and simulation listeners' performance was noted, indicating that the masking caused by gated noise is not only energetic masking. Masking release significantly increased when the number of spectral channels was increased from 4 to 12 for simulation listeners, suggesting that spectral resolution is important for masking release. Listeners were also tested for their understanding of gated sentences (sentences in quiet interrupted by periods of silence ranging from 1 to 32 Hz as a measure of auditory fusion, or the ability to integrate speech across temporal gaps. Implant and simulation listeners had significant difficulty understanding gated sentences at every gate frequency. When the number of spectral channels was increased for simulation listeners, their ability to understand gated sentences improved significantly. Findings suggest that implant listeners' difficulty understanding speech in modulated conditions is related to at least two (possibly related) factors: degraded spectral information and limitations in auditory fusion across temporal gaps.

Sleep Extension Normalizes ERP of Waking Auditory Sensory Gating in Healthy Habitually Short Sleeping Individuals

PubMed Central

Gumenyuk, Valentina; Korzyukov, Oleg; Roth, Thomas; Bowyer, Susan M.; Drake, Christopher L.

2013-01-01

Chronic sleep loss has been associated with increased daytime sleepiness, as well as impairments in memory and attentional processes. In the present study, we evaluated the neuronal changes of a pre-attentive process of wake auditory sensory gating, measured by brain event-related potential (ERP) – P50 in eight normal sleepers (NS) (habitual total sleep time (TST) 7 h 32 m) vs. eight chronic short sleeping individuals (SS) (habitual TST ≤6 h). To evaluate the effect of sleep extension on sensory gating, the extended sleep condition was performed in chronic short sleeping individuals. Thus, one week of time in bed (6 h 11 m) corresponding to habitual short sleep (hSS), and one week of extended time (∼ 8 h 25 m) in bed corresponding to extended sleep (eSS), were counterbalanced in the SS group. The gating ERP assessment was performed on the last day after each sleep condition week (normal sleep and habitual short and extended sleep), and was separated by one week with habitual total sleep time and monitored by a sleep diary. We found that amplitude of gating was lower in SS group compared to that in NS group (0.3 µV vs. 1.2 µV, at Cz electrode respectively). The results of the group × laterality interaction showed that the reduction of gating amplitude in the SS group was due to lower amplitude over the left hemisphere and central-midline sites relative to that in the NS group. After sleep extension the amplitude of gating increased in chronic short sleeping individuals relative to their habitual short sleep condition. The sleep condition × frontality interaction analysis confirmed that sleep extension significantly increased the amplitude of gating over frontal and central brain areas compared to parietal brain areas. PMID:23520548

Regional cardiac wall motion from gated myocardial perfusion SPECT studies

NASA Astrophysics Data System (ADS)

Smith, M. F.; Brigger, P.; Ferrand, S. K.; Dilsizian, V.; Bacharach, S. L.

1999-06-01

A method for estimating regional epicardial and endocardial wall motion from gated myocardial perfusion SPECT studies has been developed. The method uses epicardial and endocardial boundaries determined from four long-axis slices at each gate of the cardiac cycle. The epicardial and endocardial wall position at each time gate is computed with respect to stationary reference ellipsoids, and wall motion is measured along lines normal to these ellipsoids. An initial quantitative evaluation of the method was made using the beating heart from the dynamic mathematical cardiac torso (MCAT) phantom, with and without a 1.5-cm FWHM Gaussian blurring filter. Epicardial wall motion was generally well-estimated within a fraction of a 3.56-mm voxel, although apical motion was overestimated with the Gaussian filter. Endocardial wall motion was underestimated by about two voxels with and without the Gaussian filter. The MCAT heart phantom was modified to model hypokinetic and dyskinetic wall motion. The wall motion analysis method enabled this abnormal motion to be differentiated from normal motion. Regional cardiac wall motion also was analyzed for /sup 201/Tl patient studies. Estimated wall motion was consistent with a nuclear medicine physician's visual assessment of motion from gated long-axis slices for male and female study examples. Additional research is required for a comprehensive evaluation of the applicability of the method to patient studies with normal and abnormal wall motion.

Decoding Articulatory Features from fMRI Responses in Dorsal Speech Regions.

PubMed

Correia, Joao M; Jansma, Bernadette M B; Bonte, Milene

2015-11-11

The brain's circuitry for perceiving and producing speech may show a notable level of overlap that is crucial for normal development and behavior. The extent to which sensorimotor integration plays a role in speech perception remains highly controversial, however. Methodological constraints related to experimental designs and analysis methods have so far prevented the disentanglement of neural responses to acoustic versus articulatory speech features. Using a passive listening paradigm and multivariate decoding of single-trial fMRI responses to spoken syllables, we investigated brain-based generalization of articulatory features (place and manner of articulation, and voicing) beyond their acoustic (surface) form in adult human listeners. For example, we trained a classifier to discriminate place of articulation within stop syllables (e.g., /pa/ vs /ta/) and tested whether this training generalizes to fricatives (e.g., /fa/ vs /sa/). This novel approach revealed generalization of place and manner of articulation at multiple cortical levels within the dorsal auditory pathway, including auditory, sensorimotor, motor, and somatosensory regions, suggesting the representation of sensorimotor information. Additionally, generalization of voicing included the right anterior superior temporal sulcus associated with the perception of human voices as well as somatosensory regions bilaterally. Our findings highlight the close connection between brain systems for speech perception and production, and in particular, indicate the availability of articulatory codes during passive speech perception. Sensorimotor integration is central to verbal communication and provides a link between auditory signals of speech perception and motor programs of speech production. It remains highly controversial, however, to what extent the brain's speech perception system actively uses articulatory (motor), in addition to acoustic/phonetic, representations. In this study, we examine the role of articulatory representations during passive listening using carefully controlled stimuli (spoken syllables) in combination with multivariate fMRI decoding. Our approach enabled us to disentangle brain responses to acoustic and articulatory speech properties. In particular, it revealed articulatory-specific brain responses of speech at multiple cortical levels, including auditory, sensorimotor, and motor regions, suggesting the representation of sensorimotor information during passive speech perception. Copyright © 2015 the authors 0270-6474/15/3515015-11$15.00/0.

Normal values and standardization of parameters in nuclear cardiology: Japanese Society of Nuclear Medicine working group database.

PubMed

Nakajima, Kenichi; Matsumoto, Naoya; Kasai, Tokuo; Matsuo, Shinro; Kiso, Keisuke; Okuda, Koichi

2016-04-01

As a 2-year project of the Japanese Society of Nuclear Medicine working group activity, normal myocardial imaging databases were accumulated and summarized. Stress-rest with gated and non-gated image sets were accumulated for myocardial perfusion imaging and could be used for perfusion defect scoring and normal left ventricular (LV) function analysis. For single-photon emission computed tomography (SPECT) with multi-focal collimator design, databases of supine and prone positions and computed tomography (CT)-based attenuation correction were created. The CT-based correction provided similar perfusion patterns between genders. In phase analysis of gated myocardial perfusion SPECT, a new approach for analyzing dyssynchrony, normal ranges of parameters for phase bandwidth, standard deviation and entropy were determined in four software programs. Although the results were not interchangeable, dependency on gender, ejection fraction and volumes were common characteristics of these parameters. Standardization of (123)I-MIBG sympathetic imaging was performed regarding heart-to-mediastinum ratio (HMR) using a calibration phantom method. The HMRs from any collimator types could be converted to the value with medium-energy comparable collimators. Appropriate quantification based on common normal databases and standard technology could play a pivotal role for clinical practice and researches.

Phase matching as a gate for photon entanglement

PubMed Central

Zheltikov, A. M.

2017-01-01

Phase matching is shown to provide a tunable gate that helps discriminate entangled states of light generated by four-wave mixing (FWM) in optical fibers against uncorrelated photons originating from Raman scattering. Two types of such gates are discussed. Phase-matching gates of the first type are possible in the normal dispersion regime, where FWM sidebands can be widely tuned by high-order dispersion management, enhancing the ratio of the entangled-photon output to the Raman noise. The photon-entanglement gates of the second type are created by dual-pump cross-phase-modulation-induced FWM sideband generation and can be tuned by group-velocity mismatch of the pump fields. PMID:28703217

On the physical operation and optimization of the p-GaN gate in normally-off GaN HEMT devices

NASA Astrophysics Data System (ADS)

Efthymiou, L.; Longobardi, G.; Camuso, G.; Chien, T.; Chen, M.; Udrea, F.

2017-03-01

In this study, an investigation is undertaken to determine the effect of gate design parameters on the on-state characteristics (threshold voltage and gate turn-on voltage) of pGaN/AlGaN/GaN high electron mobility transistors (HEMTs). Design parameters considered are pGaN doping and gate metal work function. The analysis considers the effects of variations on these parameters using a TCAD model matched with experimental results. A better understanding of the underlying physics governing the operation of these devices is achieved with a view to enable better optimization of such gate designs.

The Assessment of Postural Control, Reflex Integration, and Bilateral Motor Coordination of Young Handicapped Children. Final Report.

ERIC Educational Resources Information Center

DeGangi, Georgia; Larsen, Lawrence A.

A measurement device, Assessment of Sensorimotor Integration in Preschool Children, was developed to assess postural control, reflex integration and bilateral motor integration in developmentally delayed children (3 to 5 years old). The test was administered to 113 normal children and results were compared with data collected on 23 developmentally…

Sensorimotor Assessment and Rehabilitative Apparatus

DTIC Science & Technology

2016-10-01

Support: Title: Tinnitus Retraining Treatment Trial Data Coordinating Center (TRTT) (GRANT RECENTLY ENDED) Grant Number/PI: U01 DC007422 (Scherer...Description of project’s goals: The Tinnitus Retraining Therapy Trial is a multi-center randomized controlled trial testing the efficacy of tinnitus ...retraining therapy versus usual care as a treatment for severe debilitating tinnitus in patients with functionally normal hearing. Title

[Evaluation of left ventricular diastolic function using gated SPECT with 99mTc-MIBI].

PubMed

Toba, M; Kumita, S I; Mizumura, S; Cho, K; Kijima, T; Takahama, K; Kumazaki, T

1996-04-01

Development of 3 head SPECT system and 99mTc-labeled radiopharmaceuticals enable us to evaluate left ventricular systolic function on the basis of once gated SPECT routine. This study was focused on assessment of left ventricular diastolic function using 99mTc-MIBI gated SPECT data. Twenty nine patients with ischemic heart diseases underwent 99mTc-MIBI gated SPECT and 99mTc-HSAD ventriculographic assessment of left ventricular diastolic function within 1 month. Region of interests (ROI), simultaneously calculating counts per pixel within ROI, were placed over whole myocardium of 16 serial phasic images reconstructed from gated SPECT data, following selection of the central slice within short axial images. Then, 29 patients were classified into 3 patterns of phase count curve (normal, mixed, and delayed relaxation = diastolic dysfunction). Moreover, 1/3 Count Decreasing Fraction (1/3 CDF) was calculated on the same concept as 1/3 FF. The curve pattern showed significant differences between normal and abnormal group divided on the basis of established indices such as 1/3 FF and PFR, and 1/3 CDF has correlations with 1/3 FF (r = 0.61) and PFR (r = 0.58). We concluded that the new parameters drawn from 99mTc-MIBI gated SPECT data might be feasible for evaluation of diastolic function.

Modern Clinical Research on LSD

PubMed Central

Liechti, Matthias E

2017-01-01

All modern clinical studies using the classic hallucinogen lysergic acid diethylamide (LSD) in healthy subjects or patients in the last 25 years are reviewed herein. There were five recent studies in healthy participants and one in patients. In a controlled setting, LSD acutely induced bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences. These subjective effects of LSD were mediated by the 5-HT2A receptor. LSD increased feelings of closeness to others, openness, trust, and suggestibility. LSD impaired the recognition of sad and fearful faces, reduced left amygdala reactivity to fearful faces, and enhanced emotional empathy. LSD increased the emotional response to music and the meaning of music. LSD acutely produced deficits in sensorimotor gating, similar to observations in schizophrenia. LSD had weak autonomic stimulant effects and elevated plasma cortisol, prolactin, and oxytocin levels. Resting-state functional magnetic resonance studies showed that LSD acutely reduced the integrity of functional brain networks and increased connectivity between networks that normally are more dissociated. LSD increased functional thalamocortical connectivity and functional connectivity of the primary visual cortex with other brain areas. The latter effect was correlated with subjective hallucinations. LSD acutely induced global increases in brain entropy that were associated with greater trait openness 14 days later. In patients with anxiety associated with life-threatening disease, anxiety was reduced for 2 months after two doses of LSD. In medical settings, no complications of LSD administration were observed. These data should contribute to further investigations of the therapeutic potential of LSD in psychiatry. PMID:28447622

Modern Clinical Research on LSD.

PubMed

Liechti, Matthias E

2017-10-01

All modern clinical studies using the classic hallucinogen lysergic acid diethylamide (LSD) in healthy subjects or patients in the last 25 years are reviewed herein. There were five recent studies in healthy participants and one in patients. In a controlled setting, LSD acutely induced bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences. These subjective effects of LSD were mediated by the 5-HT 2A receptor. LSD increased feelings of closeness to others, openness, trust, and suggestibility. LSD impaired the recognition of sad and fearful faces, reduced left amygdala reactivity to fearful faces, and enhanced emotional empathy. LSD increased the emotional response to music and the meaning of music. LSD acutely produced deficits in sensorimotor gating, similar to observations in schizophrenia. LSD had weak autonomic stimulant effects and elevated plasma cortisol, prolactin, and oxytocin levels. Resting-state functional magnetic resonance studies showed that LSD acutely reduced the integrity of functional brain networks and increased connectivity between networks that normally are more dissociated. LSD increased functional thalamocortical connectivity and functional connectivity of the primary visual cortex with other brain areas. The latter effect was correlated with subjective hallucinations. LSD acutely induced global increases in brain entropy that were associated with greater trait openness 14 days later. In patients with anxiety associated with life-threatening disease, anxiety was reduced for 2 months after two doses of LSD. In medical settings, no complications of LSD administration were observed. These data should contribute to further investigations of the therapeutic potential of LSD in psychiatry.

Abnormalities in brain structure and behavior in GSK-3alpha mutant mice

PubMed Central

2009-01-01

Background Glycogen synthase kinase-3 (GSK-3) is a widely expressed and highly conserved serine/threonine protein kinase encoded by two genes that generate two related proteins: GSK-3α and GSK-3β. Mice lacking a functional GSK-3α gene were engineered in our laboratory; they are viable and display insulin sensitivity. In this study, we have characterized brain functions of GSK-3α KO mice by using a well-established battery of behavioral tests together with neurochemical and neuroanatomical analysis. Results Similar to the previously described behaviours of GSK-3β+/-mice, GSK-3α mutants display decreased exploratory activity, decreased immobility time and reduced aggressive behavior. However, genetic inactivation of the GSK-3α gene was associated with: decreased locomotion and impaired motor coordination, increased grooming activity, loss of social motivation and novelty; enhanced sensorimotor gating and impaired associated memory and coordination. GSK-3α KO mice exhibited a deficit in fear conditioning, however memory formation as assessed by a passive avoidance test was normal, suggesting that the animals are sensitized for active avoidance of a highly aversive stimulus in the fear-conditioning paradigm. Changes in cerebellar structure and function were observed in mutant mice along with a significant decrease of the number and size of Purkinje cells. Conclusion Taken together, these data support a role for the GSK-3α gene in CNS functioning and possible involvement in the development of psychiatric disorders. PMID:19925672

Sex-Specific Brain Deficits in Auditory Processing in an Animal Model of Cocaine-Related Schizophrenic Disorders

PubMed Central

Broderick, Patricia A.; Rosenbaum, Taylor

2013-01-01

Cocaine is a psychostimulant in the pharmacological class of drugs called Local Anesthetics. Interestingly, cocaine is the only drug in this class that has a chemical formula comprised of a tropane ring and is, moreover, addictive. The correlation between tropane and addiction is well-studied. Another well-studied correlation is that between psychosis induced by cocaine and that psychosis endogenously present in the schizophrenic patient. Indeed, both of these psychoses exhibit much the same behavioral as well as neurochemical properties across species. Therefore, in order to study the link between schizophrenia and cocaine addiction, we used a behavioral paradigm called Acoustic Startle. We used this acoustic startle paradigm in female versus male Sprague-Dawley animals to discriminate possible sex differences in responses to startle. The startle method operates through auditory pathways in brain via a network of sensorimotor gating processes within auditory cortex, cochlear nuclei, inferior and superior colliculi, pontine reticular nuclei, in addition to mesocorticolimbic brain reward and nigrostriatal motor circuitries. This paper is the first to report sex differences to acoustic stimuli in Sprague-Dawley animals (Rattus norvegicus) although such gender responses to acoustic startle have been reported in humans (Swerdlow et al. 1997 [1]). The startle method monitors pre-pulse inhibition (PPI) as a measure of the loss of sensorimotor gating in the brain's neuronal auditory network; auditory deficiencies can lead to sensory overload and subsequently cognitive dysfunction. Cocaine addicts and schizophrenic patients as well as cocaine treated animals are reported to exhibit symptoms of defective PPI (Geyer et al., 2001 [2]). Key findings are: (a) Cocaine significantly reduced PPI in both sexes. (b) Females were significantly more sensitive than males; reduced PPI was greater in females than in males. (c) Physiological saline had no effect on startle in either sex. Thus, the data elucidate gender-specificity to the startle response in animals. Finally, preliminary studies show the effect of cocaine on acoustic startle in tandem with effects on estrous cycle. The data further suggest that hormones may play a role in these sex differences to acoustic startle reported herein. PMID:24961412

Transcranial magnetic stimulation in myoclonus of different aetiologies.

PubMed

Nardone, Raffaele; Versace, Viviana; Höller, Yvonne; Sebastianelli, Luca; Brigo, Francesco; Lochner, Piergiorgio; Golaszewski, Stefan; Saltuari, Leopold; Trinka, Eugen

2018-05-24

Transcranial magnetic stimulation (TMS) may represent a valuable tool for investigating important neurophysiological and pathophysiological aspects of myoclonus. Moreover, repetitive TMS (rTMS) can influence neural activity. In this review we performed a systematic search of all studies using TMS in order to explore cortical excitability/plasticity and rTMS for the treatment of myoclonus due to different aetiologies. We identified and reviewed 40 articles matching the inclusion criteria; 415 patients were included in these studies. The reviewed TMS studies have detected abnormalities in motor cortex excitability and sensorimotor plasticity. The most consistent finding is a decrease in intracortical inhibition. Short-interval intracortical inhibition (SICI) is reduced in myoclonic epilepsies. Unlike the juvenile and the benign myoclonus epilepsy, long-interval intracortical inhibition, interhemispheric inhibition and sensorimotor integration were altered in patients with progressive myoclonic epilepsies. In patients with myoclonus-dystonia the results are partly conflicting. Cortical membrane excitability was impaired while parameters assessing cortical synaptic activity were normal in DYT11 gene carriers. In other studies normal SICI suggests that the GABAergic cortical circuits are largely intact and that the mechanisms of myoclonus-dystonia are different from those for cortical myoclonus and other dystonic disorders. In conclusion, different TMS study protocols have provided new insights into sensorimotor plasticity and cortical excitability of the different forms of myoclonus, and have shed some light on the pathophysiology of this movement disorder. Well-defined motor cortical excitability patterns can be identified in the different disorders characterized by myoclonus, even if preliminary findings should be confirmed in future studies in larger cohorts of patients. Repetitive TMS might have therapeutic potential at least in some patients with myoclonus, similar to that reported in other neurological and psychiatric disorders. Copyright © 2018. Published by Elsevier Inc.

Functional MRI and intraoperative brain mapping to evaluate brain plasticity in patients with brain tumours and hemiparesis

PubMed Central

Roux, F; Boulanouar, K; Ibarrola, D; Tremoulet, M; Chollet, F; Berry, I

2000-01-01

OBJECTIVE—To support the hypothesis about the potential compensatory role of ipsilateral corticofugal pathways when the contralateral pathways are impaired by brain tumours.
METHODS—Retrospective analysis was carried out on the results of functional MRI (fMRI) of a selected group of five paretic patients with Rolandic brain tumours who exhibited an abnormally high ipsilateral/contralateral ratio of activation—that is, movements of the paretic hand activated predominately the ipsilateral cortex. Brain activation was achieved with a flexion extension of the fingers. Statistical parametric activation was obtained using a t test and a threshold of p<0.001. These patients, candidates for tumour resection, also underwent cortical intraoperative stimulation that was correlated to the fMRI spatial data using three dimensional reconstructions of the brain. Three patients also had postoperative control fMRI.
RESULTS—The absence of fMRI activation of the primary sensorimotor cortex normally innervating the paretic hand for the threshold chosen, was correlated with completely negative cortical responses of the cortical hand area during the operation. The preoperative fMRI activation of these patients predominantly found in the ipsilateral frontal and primary sensorimotor cortices could be related to the residual ipsilateral hand function. Postoperatively, the fMRI activation returned to more classic patterns of activation, reflecting the consequences of therapy.
CONCLUSION—In paretic patients with brain tumours, ipsilateral control could be implicated in the residual hand function, when the normal primary pathways are impaired. The possibility that functional tissue still remains in the peritumorous sensorimotor cortex even when the preoperative fMRI and the cortical intraoperative stimulations are negative, should be taken into account when planning the tumour resection and during the operation.

 PMID:10990503

Gate protective device for SOS array

NASA Technical Reports Server (NTRS)

Meyer, J. E., Jr.; Scott, J. H.

1972-01-01

Protective gate device consisting of alternating heavily doped n(+) and p(+) diffusions eliminates breakdown voltages in silicon oxide on sapphire arrays caused by electrostatic discharge from person or equipment. Diffusions are easily produced during normal double epitaxial processing. Devices with nine layers had 27-volt breakdown.

Gate tunable parallel double quantum dots in InAs double-nanowire devices

NASA Astrophysics Data System (ADS)

Baba, S.; Matsuo, S.; Kamata, H.; Deacon, R. S.; Oiwa, A.; Li, K.; Jeppesen, S.; Samuelson, L.; Xu, H. Q.; Tarucha, S.

2017-12-01

We report fabrication and characterization of InAs nanowire devices with two closely placed parallel nanowires. The fabrication process we develop includes selective deposition of the nanowires with micron scale alignment onto predefined finger bottom gates using a polymer transfer technique. By tuning the double nanowire with the finger bottom gates, we observed the formation of parallel double quantum dots with one quantum dot in each nanowire bound by the normal metal contact edges. We report the gate tunability of the charge states in individual dots as well as the inter-dot electrostatic coupling. In addition, we fabricate a device with separate normal metal contacts and a common superconducting contact to the two parallel wires and confirm the dot formation in each wire from comparison of the transport properties and a superconducting proximity gap feature for the respective wires. With the fabrication techniques established in this study, devices can be realized for more advanced experiments on Cooper-pair splitting, generation of Parafermions, and so on.

Isolated elliptically polarized attosecond soft X-ray with high-brilliance using polarization gating of harmonics from relativistic plasmas at oblique incidence.

PubMed

Chen, Zi-Yu; Li, Xiao-Ya; Li, Bo-Yuan; Chen, Min; Liu, Feng

2018-02-19

The production of intense isolated attosecond pulse is a major goal in ultrafast research. Recent advances in high harmonic generation from relativistic plasma mirrors under oblique incidence interactions gave rise to photon-rich attosecond pulses with circular or elliptical polarization. However, to achieve an isolated elliptical attosecond pulse via polarization gating using currently available long driving pulses remains a challenge, because polarization gating of high harmonics from relativistic plasmas is assumed only possible at normal or near-normal incidence. Here we numerically demonstrate a scheme around this problem. We show that via control of plasma dynamics by managing laser polarization, it is possible to gate an intense single attosecond pulse with high ellipticity extending to the soft X-ray regime at oblique incidence. This approach thus paves the way towards a powerful tool enabling high-time-resolution probe of dynamics of chiral systems and magnetic materials with current laser technology.

Loss of balance during balance beam walking elicits a multifocal theta band electrocortical response

PubMed Central

Gwin, Joseph T.; Makeig, Scott; Ferris, Daniel P.

2013-01-01

Determining the neural correlates of loss of balance during walking could lead to improved clinical assessment and treatment for individuals predisposed to falls. We used high-density electroencephalography (EEG) combined with independent component analysis (ICA) to study loss of balance during human walking. We examined 26 healthy young subjects performing heel-to-toe walking on a treadmill-mounted balance beam as well as walking on the treadmill belt (both at 0.22 m/s). ICA identified clusters of electrocortical EEG sources located in or near anterior cingulate, anterior parietal, superior dorsolateral-prefrontal, and medial sensorimotor cortex that exhibited significantly larger mean spectral power in the theta band (4–7 Hz) during walking on the balance beam compared with treadmill walking. Left and right sensorimotor cortex clusters produced significantly less power in the beta band (12–30 Hz) during walking on the balance beam compared with treadmill walking. For each source cluster, we also computed a normalized mean time/frequency spectrogram time locked to the gait cycle during loss of balance (i.e., when subjects stepped off the balance beam). All clusters except the medial sensorimotor cluster exhibited a transient increase in theta band power during loss of balance. Cluster spectrograms demonstrated that the first electrocortical indication of impending loss of balance occurred in the left sensorimotor cortex at the transition from single support to double support prior to stepping off the beam. These findings provide new insight into the neural correlates of walking balance control and could aid future studies on elderly individuals and others with balance impairments. PMID:23926037

Loss of balance during balance beam walking elicits a multifocal theta band electrocortical response.

PubMed

Sipp, Amy R; Gwin, Joseph T; Makeig, Scott; Ferris, Daniel P

2013-11-01

Determining the neural correlates of loss of balance during walking could lead to improved clinical assessment and treatment for individuals predisposed to falls. We used high-density electroencephalography (EEG) combined with independent component analysis (ICA) to study loss of balance during human walking. We examined 26 healthy young subjects performing heel-to-toe walking on a treadmill-mounted balance beam as well as walking on the treadmill belt (both at 0.22 m/s). ICA identified clusters of electrocortical EEG sources located in or near anterior cingulate, anterior parietal, superior dorsolateral-prefrontal, and medial sensorimotor cortex that exhibited significantly larger mean spectral power in the theta band (4-7 Hz) during walking on the balance beam compared with treadmill walking. Left and right sensorimotor cortex clusters produced significantly less power in the beta band (12-30 Hz) during walking on the balance beam compared with treadmill walking. For each source cluster, we also computed a normalized mean time/frequency spectrogram time locked to the gait cycle during loss of balance (i.e., when subjects stepped off the balance beam). All clusters except the medial sensorimotor cluster exhibited a transient increase in theta band power during loss of balance. Cluster spectrograms demonstrated that the first electrocortical indication of impending loss of balance occurred in the left sensorimotor cortex at the transition from single support to double support prior to stepping off the beam. These findings provide new insight into the neural correlates of walking balance control and could aid future studies on elderly individuals and others with balance impairments.

Song Selectivity in the Pallial-Basal Ganglia Song Circuit of Zebra Finches Raised Without Tutor Song Exposure

PubMed Central

Kojima, Satoshi; Doupe, Allison J.

2008-01-01

Acoustic experience critically influences auditory cortical development as well as emergence of highly selective auditory neurons in the songbird sensorimotor circuit. In adult zebra finches, these “song-selective” neurons respond better to the bird's own song (BOS) than to songs of other conspecifics. Birds learn their songs by memorizing a tutor's song and then matching auditory feedback of their voice to the tutor song memory. Song-selective neurons in the pallial-basal ganglia circuit called the anterior forebrain pathway (AFP) reflect the development of BOS. However, during learning, they also respond strongly to tutor song and are compromised in their adult selectivity when birds are prevented from matching BOS to tutor, suggesting that selectivity depends on tutor song learning as well as sensorimotor matching of BOS feedback to the tutor song memory. We examined the contribution of sensory learning of tutor song to song selectivity by recording from AFP neurons in birds reared without exposure to adult conspecifics. We found that AFP neurons in these “isolate” birds had highly tuned responses to isolate BOS. The selectivity was as high, and in the striato-pallidal nucleus Area X, even higher than that in normal birds, due to abnormally weak responsiveness to conspecific song. These results demonstrate that sensory learning of tutor song is not necessary for BOS tuning of AFP neurons. Because isolate birds develop their song via sensorimotor learning, our data further illustrate the importance of individual sensorimotor learning for song selectivity and provide insight into possible functions of song-selective neurons. PMID:17625059

Movement-related neuromagnetic fields in preschool age children.

PubMed

Cheyne, Douglas; Jobst, Cecilia; Tesan, Graciela; Crain, Stephen; Johnson, Blake

2014-09-01

We examined sensorimotor brain activity associated with voluntary movements in preschool children using a customized pediatric magnetoencephalographic system. A videogame-like task was used to generate self-initiated right or left index finger movements in 17 healthy right-handed subjects (8 females, ages 3.2-4.8 years). We successfully identified spatiotemporal patterns of movement-related brain activity in 15/17 children using beamformer source analysis and surrogate MRI spatial normalization. Readiness fields in the contralateral sensorimotor cortex began ∼0.5 s prior to movement onset (motor field, MF), followed by transient movement-evoked fields (MEFs), similar to that observed during self-paced movements in adults, but slightly delayed and with inverted source polarities. We also observed modulation of mu (8-12 Hz) and beta (15-30 Hz) oscillations in sensorimotor cortex with movement, but with different timing and a stronger frequency band coupling compared to that observed in adults. Adult-like high-frequency (70-80 Hz) gamma bursts were detected at movement onset. All children showed activation of the right superior temporal gyrus that was independent of the side of movement, a response that has not been reported in adults. These results provide new insights into the development of movement-related brain function, for an age group in which no previous data exist. The results show that children under 5 years of age have markedly different patterns of movement-related brain activity in comparison to older children and adults, and indicate that significant maturational changes occur in the sensorimotor system between the preschool years and later childhood. Copyright © 2014 Wiley Periodicals, Inc.

Altered Cortical Swallowing Processing in Patients with Functional Dysphagia: A Preliminary Study

PubMed Central

Wollbrink, Andreas; Warnecke, Tobias; Winkels, Martin; Pantev, Christo; Dziewas, Rainer

2014-01-01

Objective Current neuroimaging research on functional disturbances provides growing evidence for objective neuronal correlates of allegedly psychogenic symptoms, thereby shifting the disease concept from a psychological towards a neurobiological model. Functional dysphagia is such a rare condition, whose pathogenetic mechanism is largely unknown. In the absence of any organic reason for a patient's persistent swallowing complaints, sensorimotor processing abnormalities involving central neural pathways constitute a potential etiology. Methods In this pilot study we measured cortical swallow-related activation in 5 patients diagnosed with functional dysphagia and a matched group of healthy subjects applying magnetoencephalography. Source localization of cortical activation was done with synthetic aperture magnetometry. To test for significant differences in cortical swallowing processing between groups, a non-parametric permutation test was afterwards performed on individual source localization maps. Results Swallowing task performance was comparable between groups. In relation to control subjects, in whom activation was symmetrically distributed in rostro-medial parts of the sensorimotor cortices of both hemispheres, patients showed prominent activation of the right insula, dorsolateral prefrontal cortex and lateral premotor, motor as well as inferolateral parietal cortex. Furthermore, activation was markedly reduced in the left medial primary sensory cortex as well as right medial sensorimotor cortex and adjacent supplementary motor area (p<0.01). Conclusions Functional dysphagia - a condition with assumed normal brain function - seems to be associated with distinctive changes of the swallow-related cortical activation pattern. Alterations may reflect exaggerated activation of a widely distributed vigilance, self-monitoring and salience rating network that interferes with down-stream deglutition sensorimotor control. PMID:24586948

Quantifying the impact of respiratory-gated 4D CT acquisition on thoracic image quality: A digital phantom study

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

Bernatowicz, K., E-mail: kingab@student.ethz.ch; Knopf, A.; Lomax, A.

Purpose: Prospective respiratory-gated 4D CT has been shown to reduce tumor image artifacts by up to 50% compared to conventional 4D CT. However, to date no studies have quantified the impact of gated 4D CT on normal lung tissue imaging, which is important in performing dose calculations based on accurate estimates of lung volume and structure. To determine the impact of gated 4D CT on thoracic image quality, the authors developed a novel simulation framework incorporating a realistic deformable digital phantom driven by patient tumor motion patterns. Based on this framework, the authors test the hypothesis that respiratory-gated 4D CTmore » can significantly reduce lung imaging artifacts. Methods: Our simulation framework synchronizes the 4D extended cardiac torso (XCAT) phantom with tumor motion data in a quasi real-time fashion, allowing simulation of three 4D CT acquisition modes featuring different levels of respiratory feedback: (i) “conventional” 4D CT that uses a constant imaging and couch-shift frequency, (ii) “beam paused” 4D CT that interrupts imaging to avoid oversampling at a given couch position and respiratory phase, and (iii) “respiratory-gated” 4D CT that triggers acquisition only when the respiratory motion fulfills phase-specific displacement gating windows based on prescan breathing data. Our framework generates a set of ground truth comparators, representing the average XCAT anatomy during beam-on for each of ten respiratory phase bins. Based on this framework, the authors simulated conventional, beam-paused, and respiratory-gated 4D CT images using tumor motion patterns from seven lung cancer patients across 13 treatment fractions, with a simulated 5.5 cm{sup 3} spherical lesion. Normal lung tissue image quality was quantified by comparing simulated and ground truth images in terms of overall mean square error (MSE) intensity difference, threshold-based lung volume error, and fractional false positive/false negative rates. Results: Averaged across all simulations and phase bins, respiratory-gating reduced overall thoracic MSE by 46% compared to conventional 4D CT (p ∼ 10{sup −19}). Gating leads to small but significant (p < 0.02) reductions in lung volume errors (1.8%–1.4%), false positives (4.0%–2.6%), and false negatives (2.7%–1.3%). These percentage reductions correspond to gating reducing image artifacts by 24–90 cm{sup 3} of lung tissue. Similar to earlier studies, gating reduced patient image dose by up to 22%, but with scan time increased by up to 135%. Beam paused 4D CT did not significantly impact normal lung tissue image quality, but did yield similar dose reductions as for respiratory-gating, without the added cost in scanning time. Conclusions: For a typical 6 L lung, respiratory-gated 4D CT can reduce image artifacts affecting up to 90 cm{sup 3} of normal lung tissue compared to conventional acquisition. This image improvement could have important implications for dose calculations based on 4D CT. Where image quality is less critical, beam paused 4D CT is a simple strategy to reduce imaging dose without sacrificing acquisition time.« less

Interface trap of p-type gate integrated AlGaN/GaN heterostructure field effect transistors

NASA Astrophysics Data System (ADS)

Kim, Kyu Sang

2017-09-01

In this work, the impact of trap states at the p-(Al)GaN/AlGaN interface has been investigated for the normally-off mode p-(Al)GaN/AlGaN/GaN heterostructure field-effect transistors (HFETs) by means of frequency dependent conductance. From the current-voltage (I-V) measurement, it was found that the p-AlGaN gate integrated device has higher drain current and lower gate leakage current compared to the p-GaN gate integrated device. We obtained the interface trap density and the characteristic time constant for the p-type gate integrated HFETs under the forward gate voltage of up to 6 V. As a result, the interface trap density (characteristic time constant) of the p-GaN gate device was lower (longer) than that of the p-AlGaN. Furthermore, it was analyzed that the trap state energy level of the p-GaN gate device was located at the shallow level relative to the p-AlGaN gate device, which accounts for different gate leakage current of each devices.

Device performance of in situ steam generated gate dielectric nitrided by remote plasma nitridation

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

Al-Shareef, H. N.; Karamcheti, A.; Luo, T. Y.

2001-06-11

In situ steam generated (ISSG) oxides have recently attracted interest for use as gate dielectrics because of their demonstrated reliability improvement over oxides formed by dry oxidation. [G. Minor, G. Xing, H. S. Joo, E. Sanchez, Y. Yokota, C. Chen, D. Lopes, and A. Balakrishna, Electrochem. Soc. Symp. Proc. 99-10, 3 (1999); T. Y. Luo, H. N. Al-Shareef, G. A. Brown, M. Laughery, V. Watt, A. Karamcheti, M. D. Jackson, and H. R. Huff, Proc. SPIE 4181, 220 (2000).] We show in this letter that nitridation of ISSG oxide using a remote plasma decreases the gate leakage current of ISSGmore » oxide by an order of magnitude without significantly degrading transistor performance. In particular, it is shown that the peak normalized transconductance of n-channel devices with an ISSG oxide gate dielectric decreases by only 4% and the normalized drive current by only 3% after remote plasma nitridation (RPN). In addition, it is shown that the reliability of the ISSG oxide exhibits only a small degradation after RPN. These observations suggest that the ISSG/RPN process holds promise for gate dielectric applications. {copyright} 2001 American Institute of Physics.« less

Chiral tunneling modulated by a time-periodic potential on the surface states of a topological insulator

PubMed Central

Li, Yuan; Jalil, Mansoor B. A.; Tan, S. G.; Zhao, W.; Bai, R.; Zhou, G. H.

2014-01-01

Time-periodic perturbation can be used to modify the transport properties of the surface states of topological insulators, specifically their chiral tunneling property. Using the scattering matrix method, we study the tunneling transmission of the surface states of a topological insulator under the influence of a time-dependent potential and finite gate bias voltage. It is found that perfect transmission is obtained for electrons which are injected normally into the time-periodic potential region in the absence of any bias voltage. However, this signature of Klein tunneling is destroyed when a bias voltage is applied, with the transmission probability of normally incident electrons decreasing with increasing gate bias voltage. Likewise, the overall conductance of the system decreases significantly when a gate bias voltage is applied. The characteristic left-handed helicity of the transmitted spin polarization is also broken by the finite gate bias voltage. In addition, the time-dependent potential modifies the large-angle transmission profile, which exhibits an oscillatory or resonance-like behavior. Finally, time-dependent transport modes (with oscillating potential in the THz frequency) can result in enhanced overall conductance, irrespective of the presence or absence of the gate bias voltage. PMID:24713634

Myocardial perfusion and left ventricular function indices assessed by gated myocardial perfusion SPECT in methamphetamine abusers.

PubMed

Dadpour, Bita; Dabbagh Kakhki, Vahid R; Afshari, Reza; Dorri-Giv, Masoumeh; Mohajeri, Seyed A R; Ghahremani, Somayeh

2016-12-01

Methamphetamine (MA) is associated with alterations of cardiac structure and function, although it is less known. In this study, we assessed possible abnormality in myocardial perfusion and left ventricular function using gated myocardial perfusion SPECT. Fifteen patients with MA abuse, on the basis of Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) MA dependency determined by Structured Clinical Interview for DSM-IV, underwent 2-day dipyridamole stress/rest Tc-sestamibi gated myocardial perfusion SPECT. An average daily dose of MA use was 0.91±1.1 (0.2-4) g. The duration of MA use was 3.4±2.1 (1-7) years. In visual and semiquantitative analyses, all patients had normal gated myocardial perfusion SPECT, with no perfusion defects. In all gated SPECT images, there was no abnormality in left ventricular wall motion and thickening. All summed stress scores and summed rest scores were below 3. Calculated left ventricular functional indices including the end-diastolic volume, end-systolic volume, and left ventricular ejection fraction were normal. Many cardiac findings because of MA mentioned in previous reports are less likely because of significant epicardial coronary artery stenosis.

Behavioural Adaptation to diminished Gravity in Fish - a Parabolic Aircraft Flight Study

NASA Astrophysics Data System (ADS)

Forster, A.; Anken, R.; Hilbig, R.

During the micro gravity phases in the course of parabolic aircraft flights PFs some fish of a given batch were frequently shown to exhibit sensorimotor disorders in terms of revealing so-called looping responses LR or spinning movements SM both forms of motion sickness a kinetosis In order to gain some insights into the time-course of the behavioural adaptation towards diminished gravity in total 272 larval cichlid fish Oreochromis mossambicus were subjected to PFs and their respective behaviour was monitored With the onset of the first parabola P1 15 9 of the animals revealed a kinetotic behaviour whereas kinetoses were shown in 6 5 1 5 and 1 of the animals in P5 P10 and P15 With P20 the animals had adapted completely 0 swimming kinetotically Since the relative decrease of kinetotic animals was especially prominent from P5 to P10 a detailed analysis of the behaviour was undertaken Regarding SM a ratio of 2 9 in P5 decreased to 0 5 in P10 Virtually all individuals showing a SM in P5 had regained a normal behaviour with P10 The SM animals in P10 had all exhibited a normal swimming behaviour in P5 The ratio of LR-fish also decreased from P5 3 6 to P10 1 0 In contrast to the findings regarding SM numerous LM specimens did not regain a normal postural control and only very few animals behaving normally in P5 began to sport a LM behaviour by P10 Summarizing most kinetotic animals rapidly adapted to diminished gravity but few individual fish who swam normally at the beginning of the flights may loose sensorimotor control

How do voltage-gated sodium channels enhance migration and invasiveness in cancer cells?

PubMed

Besson, Pierre; Driffort, Virginie; Bon, Émeline; Gradek, Frédéric; Chevalier, Stéphan; Roger, Sébastien

2015-10-01

Voltage-gated sodium channels are abnormally expressed in tumors, often as neonatal isoforms, while they are not expressed, or only at a low level, in the matching normal tissue. The level of their expression and their activity is related to the aggressiveness of the disease and to the formation of metastases. A vast knowledge on the regulation of their expression and functioning has been accumulated in normal excitable cells. This helped understand their regulation in cancer cells. However, how voltage-gated sodium channels impose a pro-metastatic behavior to cancer cells is much less documented. This aspect will be addressed in the review. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers. Copyright © 2015 Elsevier B.V. All rights reserved.

Protective circuit for thyristor controlled systems and thyristor converter embodying such protective circuit

DOEpatents

Downhower, Jr., Francis H.; Finlayson, Paul T.

1984-04-10

A snubber circuit coupled across each thyristor to be gated in a chain of thyristors determines the critical output of a NOR LATCH whenever one snubber circuit could not be charged and discharged under normal gating conditions because of a short failure.

Sensorimotor event: an approach to the dynamic, embodied, and embedded nature of sensorimotor cognition

PubMed Central

Vilarroya, Oscar

2014-01-01

In this paper, I explore the notion of sensorimotor event as the building block of sensorimotor cognition. A sensorimotor event is presented here as a neurally controlled event that recruits those processes and elements that are necessary to address the demands of the situation in which the individual is involved. The notion of sensorimotor event is intended to subsume the dynamic, embodied, and embedded nature of sensorimotor cognition, in agreement with the satisficing and bricoleur approach to sensorimotor cognition presented elsewhere (Vilarroya, 2012). In particular, the notion of sensorimotor event encompasses those relevant neural processes, but also those bodily and environmental elements, that are necessary to deal with the situation in which the individual is involved. This continuum of neural processes as well as bodily and environmental elements can be characterized, and this characterization is considered the basis for the identification of the particular sensorimotor event. Among other consequences, the notion of sensorimotor event suggests a different approach to the classical account of sensory-input mapping onto a motor output. Instead of characterizing how a neural system responds to an external input, the idea defended here is to characterize how system-in-an-environment responds to its antecedent situation. PMID:24427133

Correlation between border traps and exposed surface properties in gate recessed normally-off Al2O3/GaN MOSFET

NASA Astrophysics Data System (ADS)

Yin, Ruiyuan; Li, Yue; Sun, Yu; Wen, Cheng P.; Hao, Yilong; Wang, Maojun

2018-06-01

We report the effect of the gate recess process and the surface of as-etched GaN on the gate oxide quality and first reveal the correlation between border traps and exposed surface properties in normally-off Al2O3/GaN MOSFET. The inductively coupled plasma (ICP) dry etching gate recess with large damage presents a rough and active surface that is prone to form detrimental GaxO validated by atomic force microscopy and X-ray photoelectron spectroscopy. Lower drain current noise spectral density of the 1/f form and less dispersive ac transconductance are observed in GaN MOSFETs fabricated with oxygen assisted wet etching compared with devices based on ICP dry etching. One decade lower density of border traps is extracted in devices with wet etching according to the carrier number fluctuation model, which is consistent with the result from the ac transconductance method. Both methods show that the density of border traps is skewed towards the interface, indicating that GaxO is of higher trap density than the bulk gate oxide. GaxO located close to the interface is the major location of border traps. The damage-free oxidation assisted wet etching gate recess technique presents a relatively smooth and stable surface, resulting in lower border trap density, which would lead to better MOS channel quality and improved device reliability.

Hybrid circuit achieves pulse regeneration with low power drain

NASA Technical Reports Server (NTRS)

Cancro, C. A.

1965-01-01

Hybrid tunnel diode-transistor circuit provides a solid-state, low power drain pulse regenerator, frequency limiter, or gated oscillator. When the feedback voltage exceeds the input voltage, the circuit functions as a pulse normalizer or a frequency limiter. If the circuit is direct coupled, it functions as a gated oscillator.

Gate-tuned Josephson effect on the surface of a topological insulator

PubMed Central

2014-01-01

In the study, we investigate the Josephson supercurrent of a superconductor/normal metal/superconductor junction on the surface of a topological insulator, where a gate electrode is attached to the normal metal. It is shown that the Josephson supercurrent not only can be tuned largely by the temperature but also is related to the potential and the length of the weak-link region. Especially, the asymmetry excess critical supercurrent, oscillatory character, and plateau-like structure have been revealed. We except those phenomena that can be observed in the recent experiment. PMID:25249827

Sleep and vestibular adaptation: implications for function in microgravity

NASA Technical Reports Server (NTRS)

Hobson, J. A.; Stickgold, R.; Pace-Schott, E. F.; Leslie, K. R.

1998-01-01

Optimal human performance depends upon integrated sensorimotor and cognitive functions, both of which are known to be exquisitely sensitive to loss of sleep. Under the microgravity conditions of space flight, adaptation of both sensorimotor (especially vestibular) and cognitive functions (especially orientation) must occur quickly--and be maintained--despite any concurrent disruptions of sleep that may be caused by microgravity itself, or by the uncomfortable sleeping conditions of the spacecraft. It is the three-way interaction between sleep quality, general work efficiency, and sensorimotor integration that is the subject of this paper and the focus of new work in our laboratory. To record sleep under field conditions including microgravity, we utilize a novel system called the Nightcap that we have developed and extensively tested on normal and sleep-disordered subjects. To perturb the vestibular system in ground-based studies, we utilize a variety of experimental conditions including optokinetic stimulation and both minifying and reversing goggle paradigms that have been extensively studied in relation to plasticity of the vestibulo-ocular reflex. Using these techniques we will test the hypothesis that vestibular adaptation both provokes and is enhanced by REM sleep under both ground-based and space conditions. In this paper we describe preliminary results of some of our studies.

Sensory augmentation: integration of an auditory compass signal into human perception of space

PubMed Central

Schumann, Frank; O’Regan, J. Kevin

2017-01-01

Bio-mimetic approaches to restoring sensory function show great promise in that they rapidly produce perceptual experience, but have the disadvantage of being invasive. In contrast, sensory substitution approaches are non-invasive, but may lead to cognitive rather than perceptual experience. Here we introduce a new non-invasive approach that leads to fast and truly perceptual experience like bio-mimetic techniques. Instead of building on existing circuits at the neural level as done in bio-mimetics, we piggy-back on sensorimotor contingencies at the stimulus level. We convey head orientation to geomagnetic North, a reliable spatial relation not normally sensed by humans, by mimicking sensorimotor contingencies of distal sounds via head-related transfer functions. We demonstrate rapid and long-lasting integration into the perception of self-rotation. Short training with amplified or reduced rotation gain in the magnetic signal can expand or compress the perceived extent of vestibular self-rotation, even with the magnetic signal absent in the test. We argue that it is the reliability of the magnetic signal that allows vestibular spatial recalibration, and the coding scheme mimicking sensorimotor contingencies of distal sounds that permits fast integration. Hence we propose that contingency-mimetic feedback has great potential for creating sensory augmentation devices that achieve fast and genuinely perceptual experiences. PMID:28195187

Sensorimotor adaptation is influenced by background music.

PubMed

Bock, Otmar

2010-06-01

It is well established that listening to music can modify subjects' cognitive performance. The present study evaluates whether this so-called Mozart Effect extends beyond cognitive tasks and includes sensorimotor adaptation. Three subject groups listened to musical pieces that in the author's judgment were serene, neutral, or sad, respectively. This judgment was confirmed by the subjects' introspective reports. While listening to music, subjects engaged in a pointing task that required them to adapt to rotated visual feedback. All three groups adapted successfully, but the speed and magnitude of adaptive improvement was more pronounced with serene music than with the other two music types. In contrast, aftereffects upon restoration of normal feedback were independent of music type. These findings support the existence of a "Mozart effect" for strategic movement control, but not for adaptive recalibration. Possibly, listening to music modifies neural activity in an intertwined cognitive-emotional network.

Sex differences in the influence of body mass index on anatomical architecture of brain networks.

PubMed

Gupta, A; Mayer, E A; Hamadani, K; Bhatt, R; Fling, C; Alaverdyan, M; Torgerson, C; Ashe-McNalley, C; Van Horn, J D; Naliboff, B; Tillisch, K; Sanmiguel, C P; Labus, J S

2017-08-01

The brain has a central role in regulating ingestive behavior in obesity. Analogous to addiction behaviors, an imbalance in the processing of rewarding and salient stimuli results in maladaptive eating behaviors that override homeostatic needs. We performed network analysis based on graph theory to examine the association between body mass index (BMI) and network measures of integrity, information flow and global communication (centrality) in reward, salience and sensorimotor regions and to identify sex-related differences in these parameters. Structural and diffusion tensor imaging were obtained in a sample of 124 individuals (61 males and 63 females). Graph theory was applied to calculate anatomical network properties (centrality) for regions of the reward, salience and sensorimotor networks. General linear models with linear contrasts were performed to test for BMI and sex-related differences in measures of centrality, while controlling for age. In both males and females, individuals with high BMI (obese and overweight) had greater anatomical centrality (greater connectivity) of reward (putamen) and salience (anterior insula) network regions. Sex differences were observed both in individuals with normal and elevated BMI. In individuals with high BMI, females compared to males showed greater centrality in reward (amygdala, hippocampus and nucleus accumbens) and salience (anterior mid-cingulate cortex) regions, while males compared to females had greater centrality in reward (putamen) and sensorimotor (posterior insula) regions. In individuals with increased BMI, reward, salience and sensorimotor network regions are susceptible to topological restructuring in a sex-related manner. These findings highlight the influence of these regions on integrative processing of food-related stimuli and increased ingestive behavior in obesity, or in the influence of hedonic ingestion on brain topological restructuring. The observed sex differences emphasize the importance of considering sex differences in obesity pathophysiology.

Sex Differences in the Influence of Body Mass Index on Anatomical Architecture of Brain Networks

PubMed Central

Gupta, Arpana; Mayer, Emeran A.; Hamadani, Kareem; Bhatt, Ravi; Fling, Connor; Alaverdyan, Mher; Torgenson, Carinna; Ashe-McNalley, Cody; Van Horn, John D; Naliboff, Bruce; Tillisch, Kirsten; Sanmiguel, Claudia P.; Labus, Jennifer S.

2017-01-01

Background/Objective The brain plays a central role in regulating ingestive behavior in obesity. Analogous to addiction behaviors, an imbalance in the processing of rewarding and salient stimuli results in maladaptive eating behaviors that override homeostatic needs. We performed network analysis based on graph theory to examine the association between body mass index (BMI) and network measures of integrity, information flow, and global communication (centrality) in reward, salience and sensorimotor regions, and to identify sex-related differences in these parameters. Subjects/Methods Structural and diffusion tensor imaging were obtained in a sample of 124 individuals (61 males and 63 females). Graph theory was applied to calculate anatomical network properties (centrality) for regions of the reward, salience, and sensorimotor networks. General linear models with linear contrasts were performed to test for BMI and sex-related differences in measures of centrality, while controlling for age. Results In both males and females, individuals with high BMI (obese and overweight) had greater anatomical centrality (greater connectivity) of reward (putamen) and salience (anterior insula) network regions. Sex differences were observed both in individuals with normal and elevated BMI. In individuals with high BMI, females compared to males showed greater centrality in reward (amygdala, hippocampus, nucleus accumbens) and salience (anterior mid cingulate cortex) regions, while males compared to females had greater centrality in reward (putamen) and sensorimotor (posterior insula) regions. Conclusions In individuals with increased BMI, reward, salience, and sensorimotor network regions are susceptible to topological restructuring in a sex related manner. These findings highlight the influence of these regions on integrative processing of food-related stimuli and increased ingestive behavior in obesity, or in the influence of hedonic ingestion on brain topological restructuring. The observed sex differences emphasize the importance of considering sex differences in obesity pathophysiology. PMID:28360430

Sensorimotor adaptation of point-to-point arm movements after spaceflight: the role of internal representation of gravity force in trajectory planning.

PubMed

Gaveau, Jérémie; Paizis, Christos; Berret, Bastien; Pozzo, Thierry; Papaxanthis, Charalambos

2011-08-01

After an exposure to weightlessness, the central nervous system operates under new dynamic and sensory contexts. To find optimal solutions for rapid adaptation, cosmonauts have to decide whether parameters from the world or their body have changed and to estimate their properties. Here, we investigated sensorimotor adaptation after a spaceflight of 10 days. Five cosmonauts performed forward point-to-point arm movements in the sagittal plane 40 days before and 24 and 72 h after the spaceflight. We found that, whereas the shape of hand velocity profiles remained unaffected after the spaceflight, hand path curvature significantly increased 1 day after landing and returned to the preflight level on the third day. Control experiments, carried out by 10 subjects under normal gravity conditions, showed that loading the arm with varying loads (from 0.3 to 1.350 kg) did not affect path curvature. Therefore, changes in path curvature after spaceflight cannot be the outcome of a control process based on the subjective feeling that arm inertia was increased. By performing optimal control simulations, we found that arm kinematics after exposure to microgravity corresponded to a planning process that overestimated the gravity level and optimized movements in a hypergravity environment (∼1.4 g). With time and practice, the sensorimotor system was recalibrated to Earth's gravity conditions, and cosmonauts progressively generated accurate estimations of the body state, gravity level, and sensory consequences of the motor commands (72 h). These observations provide novel insights into how the central nervous system evaluates body (inertia) and environmental (gravity) states during sensorimotor adaptation of point-to-point arm movements after an exposure to weightlessness.

Polarization-Engineered Ga-Face GaN-Based Heterostructures for Normally-Off Heterostructure Field-Effect Transistors

NASA Astrophysics Data System (ADS)

Kim, Hyeongnam; Nath, Digbijoy; Rajan, Siddharth; Lu, Wu

2013-01-01

Polarization-engineered Ga-face GaN-based heterostructures with a GaN cap layer and an AlGaN/ p-GaN back barrier have been designed for normally-off field-effect transistors (FETs). The simulation results show that an unintentionally doped GaN cap and p-GaN layer in the buffer primarily deplete electrons in the channel and the Al0.2Ga0.8N back barrier helps to pinch off the channel. Experimentally, we have demonstrated a normally-off GaN-based field-effect transistor on the designed GaN cap/Al0.3Ga0.7N/GaN channel/Al0.2Ga0.8N/ p-GaN/GaN heterostructure. A positive threshold voltage of 0.2 V and maximum transconductance of 2.6 mS/mm were achieved for 80- μm-long gate devices. The device fabrication process does not require a dry etching process for gate recessing, while highly selective etching of the GaN cap against a very thin Al0.3GaN0.7N top barrier has to be performed to create a two-dimensional electron gas for both the ohmic and access regions. A self-aligned, selective etch of the GaN cap in the access region is introduced, using the gate metal as an etch mask. The absence of gate recess etching is promising for uniform and repeatable threshold voltage control in normally-off AlGaN/GaN heterostructure FETs for power switching applications.

A simulation for the gated weir opening of Wonokromo River, Rungkut District, Surabaya

NASA Astrophysics Data System (ADS)

Handajani, N.; Wahjudijanto, I.; Mu'afi, M.

2018-01-01

The gated weir is a weir that the crest elevation could be operated based on the flow through the river. The upstream water level of the gated weir could be controlled with gate opening or closing. This study applied a simulation with HEC-RAS 4,0 program in order to know the river hydraulic condition after the gated weir has built. According to the rainfall intensity from each sub-watershed, Distribution Log Pearson III with return period 50 years (Q50) was determined to calculate the design flood discharge. By using Rational Method, the design flood discharge is 470 m3/s. The Results show that capacity of the river is able to accomodate Q50 with discharge 470 m3/s and the gate should be fully opened during flood. This condition could passed the normal discharge at + 5.00 m elevation.

Cytoplasmic Domains and Voltage-Dependent Potassium Channel Gating

PubMed Central

Barros, Francisco; Domínguez, Pedro; de la Peña, Pilar

2012-01-01

The basic architecture of the voltage-dependent K+ channels (Kv channels) corresponds to a transmembrane protein core in which the permeation pore, the voltage-sensing components and the gating machinery (cytoplasmic facing gate and sensor–gate coupler) reside. Usually, large protein tails are attached to this core, hanging toward the inside of the cell. These cytoplasmic regions are essential for normal channel function and, due to their accessibility to the cytoplasmic environment, constitute obvious targets for cell-physiological control of channel behavior. Here we review the present knowledge about the molecular organization of these intracellular channel regions and their role in both setting and controlling Kv voltage-dependent gating properties. This includes the influence that they exert on Kv rapid/N-type inactivation and on activation/deactivation gating of Shaker-like and eag-type Kv channels. Some illustrative examples about the relevance of these cytoplasmic domains determining the possibilities for modulation of Kv channel gating by cellular components are also considered. PMID:22470342

Quantification of calcium using localized normalization on laser-induced breakdown spectroscopy data

NASA Astrophysics Data System (ADS)

Sabri, Nursalwanie Mohd; Haider, Zuhaib; Tufail, Kashif; Aziz, Safwan; Ali, Jalil; Wahab, Zaidan Abdul; Abbas, Zulkifly

2017-03-01

This paper focuses on localized normalization for improved calibration curves in laser-induced breakdown spectroscopy (LIBS) measurements. The calibration curves have been obtained using five samples consisting of different concentrations of calcium (Ca) in potassium bromide (KBr) matrix. The work has utilized Q-switched Nd:YAG laser installed in LIBS2500plus system with fundamental wavelength and laser energy of 650 mJ. Optimization of gate delay can be obtained from signal-to-background ratio (SBR) of Ca II 315.9 and 317.9 nm. The optimum conditions are determined in which having high spectral intensity and SBR. The highest spectral lines of ionic and emission lines of Ca at gate delay of 0.83 µs. From SBR, the optimized gate delay is at 5.42 µs for both Ca II spectral lines. Calibration curves consist of three parts; original intensity from LIBS experimentation, normalization and localized normalization of the spectral line intensity. The R2 values of the calibration curves plotted using locally normalized intensities of Ca I 610.3, 612.2 and 616.2 nm spectral lines are 0.96329, 0.97042, and 0.96131, respectively. The enhancement from calibration curves using the regression coefficient allows more accurate analysis in LIBS. At the request of all authors of the paper, and with the agreement of the Proceedings Editor, an updated version of this article was published on 24 May 2017.

Motion mitigation for lung cancer patients treated with active scanning proton therapy

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

Grassberger, Clemens, E-mail: Grassberger.Clemens@mgh.harvard.edu; Dowdell, Stephen; Sharp, Greg

2015-05-15

Purpose: Motion interplay can affect the tumor dose in scanned proton beam therapy. This study assesses the ability of rescanning and gating to mitigate interplay effects during lung treatments. Methods: The treatments of five lung cancer patients [48 Gy(RBE)/4fx] with varying tumor size (21.1–82.3 cm{sup 3}) and motion amplitude (2.9–30.6 mm) were simulated employing 4D Monte Carlo. The authors investigated two spot sizes (σ ∼ 12 and ∼3 mm), three rescanning techniques (layered, volumetric, breath-sampled volumetric) and respiratory gating with a 30% duty cycle. Results: For 4/5 patients, layered rescanning 6/2 times (for the small/large spot size) maintains equivalent uniformmore » dose within the target >98% for a single fraction. Breath sampling the timing of rescanning is ∼2 times more effective than the same number of continuous rescans. Volumetric rescanning is sensitive to synchronization effects, which was observed in 3/5 patients, though not for layered rescanning. For the large spot size, rescanning compared favorably with gating in terms of time requirements, i.e., 2x-rescanning is on average a factor ∼2.6 faster than gating for this scenario. For the small spot size however, 6x-rescanning takes on average 65% longer compared to gating. Rescanning has no effect on normal lung V{sub 20} and mean lung dose (MLD), though it reduces the maximum lung dose by on average 6.9 ± 2.4/16.7 ± 12.2 Gy(RBE) for the large and small spot sizes, respectively. Gating leads to a similar reduction in maximum dose and additionally reduces V{sub 20} and MLD. Breath-sampled rescanning is most successful in reducing the maximum dose to the normal lung. Conclusions: Both rescanning (2–6 times, depending on the beam size) as well as gating was able to mitigate interplay effects in the target for 4/5 patients studied. Layered rescanning is superior to volumetric rescanning, as the latter suffers from synchronization effects in 3/5 patients studied. Gating minimizes the irradiated volume of normal lung more efficiently, while breath-sampled rescanning is superior in reducing maximum doses to organs at risk.« less

Behavioral, Brain Imaging and Genomic Measures to Predict Functional Outcomes Post - Bed Rest and Spaceflight

NASA Technical Reports Server (NTRS)

Mulavara, A. P.; DeDios, Y. E.; Gadd, N. E.; Caldwell, E. E.; Batson, C. D.; Goel, R.; Seidler, R. D.; Oddsson, L.; Zanello, S.; Clarke, T.;

Learning to perceive in the sensorimotor approach: Piaget’s theory of equilibration interpreted dynamically

PubMed Central

Di Paolo, Ezequiel Alejandro; Barandiaran, Xabier E.; Beaton, Michael; Buhrmann, Thomas

2014-01-01

Learning to perceive is faced with a classical paradox: if understanding is required for perception, how can we learn to perceive something new, something we do not yet understand? According to the sensorimotor approach, perception involves mastery of regular sensorimotor co-variations that depend on the agent and the environment, also known as the “laws” of sensorimotor contingencies (SMCs). In this sense, perception involves enacting relevant sensorimotor skills in each situation. It is important for this proposal that such skills can be learned and refined with experience and yet up to this date, the sensorimotor approach has had no explicit theory of perceptual learning. The situation is made more complex if we acknowledge the open-ended nature of human learning. In this paper we propose Piaget’s theory of equilibration as a potential candidate to fulfill this role. This theory highlights the importance of intrinsic sensorimotor norms, in terms of the closure of sensorimotor schemes. It also explains how the equilibration of a sensorimotor organization faced with novelty or breakdowns proceeds by re-shaping pre-existing structures in coupling with dynamical regularities of the world. This way learning to perceive is guided by the equilibration of emerging forms of skillful coping with the world. We demonstrate the compatibility between Piaget’s theory and the sensorimotor approach by providing a dynamical formalization of equilibration to give an explicit micro-genetic account of sensorimotor learning and, by extension, of how we learn to perceive. This allows us to draw important lessons in the form of general principles for open-ended sensorimotor learning, including the need for an intrinsic normative evaluation by the agent itself. We also explore implications of our micro-genetic account at the personal level. PMID:25126065

Learning to perceive in the sensorimotor approach: Piaget's theory of equilibration interpreted dynamically.

PubMed

Di Paolo, Ezequiel Alejandro; Barandiaran, Xabier E; Beaton, Michael; Buhrmann, Thomas

2014-01-01

if understanding is required for perception, how can we learn to perceive something new, something we do not yet understand? According to the sensorimotor approach, perception involves mastery of regular sensorimotor co-variations that depend on the agent and the environment, also known as the "laws" of sensorimotor contingencies (SMCs). In this sense, perception involves enacting relevant sensorimotor skills in each situation. It is important for this proposal that such skills can be learned and refined with experience and yet up to this date, the sensorimotor approach has had no explicit theory of perceptual learning. The situation is made more complex if we acknowledge the open-ended nature of human learning. In this paper we propose Piaget's theory of equilibration as a potential candidate to fulfill this role. This theory highlights the importance of intrinsic sensorimotor norms, in terms of the closure of sensorimotor schemes. It also explains how the equilibration of a sensorimotor organization faced with novelty or breakdowns proceeds by re-shaping pre-existing structures in coupling with dynamical regularities of the world. This way learning to perceive is guided by the equilibration of emerging forms of skillful coping with the world. We demonstrate the compatibility between Piaget's theory and the sensorimotor approach by providing a dynamical formalization of equilibration to give an explicit micro-genetic account of sensorimotor learning and, by extension, of how we learn to perceive. This allows us to draw important lessons in the form of general principles for open-ended sensorimotor learning, including the need for an intrinsic normative evaluation by the agent itself. We also explore implications of our micro-genetic account at the personal level.

Feasibility of quantification of the distribution of blood flow in the normal human fetal circulation using CMR: a cross-sectional study.

PubMed

Seed, Mike; van Amerom, Joshua F P; Yoo, Shi-Joon; Al Nafisi, Bahiyah; Grosse-Wortmann, Lars; Jaeggi, Edgar; Jansz, Michael S; Macgowan, Christopher K

2012-11-26

We present the first phase contrast (PC) cardiovascular magnetic resonance (CMR) measurements of the distribution of blood flow in twelve late gestation human fetuses. These were obtained using a retrospective gating technique known as metric optimised gating (MOG). A validation experiment was performed in five adult volunteers where conventional cardiac gating was compared with MOG. Linear regression and Bland Altman plots were used to compare MOG with the gold standard of conventional gating. Measurements using MOG were then made in twelve normal fetuses at a median gestational age of 37 weeks (range 30-39 weeks). Flow was measured in the major fetal vessels and indexed to the fetal weight. There was good correlation between the conventional gated and MOG measurements in the adult validation experiment (R=0.96). Mean flows in ml/min/kg with standard deviations in the major fetal vessels were as follows: combined ventricular output (CVO) 540 ± 101, main pulmonary artery (MPA) 327 ± 68, ascending aorta (AAo) 198 ± 38, superior vena cava (SVC) 147 ± 46, ductus arteriosus (DA) 220 ± 39,pulmonary blood flow (PBF) 106 ± 59,descending aorta (DAo) 273 ± 85, umbilical vein (UV) 160 ± 62, foramen ovale (FO)107 ± 54. Results expressed as mean percentages of the CVO with standard deviations were as follows: MPA 60 ± 4, AAo37 ± 4, SVC 28 ± 7, DA 41 ± 8, PBF 19 ± 10, DAo50 ± 12, UV 30 ± 9, FO 21 ± 12. This study demonstrates how PC CMR with MOG is a feasible technique for measuring the distribution of the normal human fetal circulation in late pregnancy. Our preliminary results are in keeping with findings from previous experimental work in fetal lambs.

Enhancing ejection fraction measurement through 4D respiratory motion compensation in cardiac PET imaging

NASA Astrophysics Data System (ADS)

Tang, Jing; Wang, Xinhui; Gao, Xiangzhen; Segars, W. Paul; Lodge, Martin A.; Rahmim, Arman

2017-06-01

ECG gated cardiac PET imaging measures functional parameters such as left ventricle (LV) ejection fraction (EF), providing diagnostic and prognostic information for management of patients with coronary artery disease (CAD). Respiratory motion degrades spatial resolution and affects the accuracy in measuring the LV volumes for EF calculation. The goal of this study is to systematically investigate the effect of respiratory motion correction on the estimation of end-diastolic volume (EDV), end-systolic volume (ESV), and EF, especially on the separation of normal and abnormal EFs. We developed a respiratory motion incorporated 4D PET image reconstruction technique which uses all gated-frame data to acquire a motion-suppressed image. Using the standard XCAT phantom and two individual-specific volunteer XCAT phantoms, we simulated dual-gated myocardial perfusion imaging data for normally and abnormally beating hearts. With and without respiratory motion correction, we measured the EDV, ESV, and EF from the cardiac-gated reconstructed images. For all the phantoms, the estimated volumes increased and the biases significantly reduced with motion correction compared with those without. Furthermore, the improvement of ESV measurement in the abnormally beating heart led to better separation of normal and abnormal EFs. The simulation study demonstrated the significant effect of respiratory motion correction on cardiac imaging data with motion amplitude as small as 0.7 cm. The larger the motion amplitude the more improvement respiratory motion correction brought about on the EF measurement. Using data-driven respiratory gating, we also demonstrated the effect of respiratory motion correction on estimating the above functional parameters from list mode patient data. Respiratory motion correction has been shown to improve the accuracy of EF measurement in clinical cardiac PET imaging.

Direct activation of the olfactory cyclic nucleotide-gated channel through modification of sulfhydryl groups by NO compounds.

PubMed

Broillet, M C; Firestein, S

1996-02-01

The activation of a cyclic nucleotide-gated channel is the final step in sensory transduction in olfaction. Normally, this channel is opened by the intracellular cyclic nucleotide second messenger cAMP or cGMP. However, in single channel recordings we found that donors of nitric oxide, a putative intercellular messenger, could directly activate the native olfactory neuron channel. Its action was independent of the presence of the normal ligand and did not involve the cyclic nucleotide binding site, suggesting an alternate site on the molecule that is critical in channel gating. The biochemical pathway appears to utilize nitric oxide in one of its alternate redox states, the nitrosonium ion, transnitrosylating a free sulfhydryl group belonging to a cysteine residue tentatively identified as being in the region linking the S6 transmembrane domain to the ligand binding domain.

Rehabilitation robots for the treatment of sensorimotor deficits: a neurophysiological perspective.

PubMed

Gassert, Roger; Dietz, Volker

2018-06-05

The past decades have seen rapid and vast developments of robots for the rehabilitation of sensorimotor deficits after damage to the central nervous system (CNS). Many of these innovations were technology-driven, limiting their clinical application and impact. Yet, rehabilitation robots should be designed on the basis of neurophysiological insights underlying normal and impaired sensorimotor functions, which requires interdisciplinary collaboration and background knowledge.Recovery of sensorimotor function after CNS damage is based on the exploitation of neuroplasticity, with a focus on the rehabilitation of movements needed for self-independence. This requires a physiological limb muscle activation that can be achieved through functional arm/hand and leg movement exercises and the activation of appropriate peripheral receptors. Such considerations have already led to the development of innovative rehabilitation robots with advanced interaction control schemes and the use of integrated sensors to continuously monitor and adapt the support to the actual state of patients, but many challenges remain. For a positive impact on outcome of function, rehabilitation approaches should be based on neurophysiological and clinical insights, keeping in mind that recovery of function is limited. Consequently, the design of rehabilitation robots requires a combination of specialized engineering and neurophysiological knowledge. When appropriately applied, robot-assisted therapy can provide a number of advantages over conventional approaches, including a standardized training environment, adaptable support and the ability to increase therapy intensity and dose, while reducing the physical burden on therapists. Rehabilitation robots are thus an ideal means to complement conventional therapy in the clinic, and bear great potential for continued therapy and assistance at home using simpler devices.This review summarizes the evolution of the field of rehabilitation robotics, as well as the current state of clinical evidence. It highlights fundamental neurophysiological factors influencing the recovery of sensorimotor function after a stroke or spinal cord injury, and discusses their implications for the development of effective rehabilitation robots. It thus provides insights on essential neurophysiological mechanisms to be considered for a successful development and clinical inclusion of robots in rehabilitation.

Atomic layer deposition of sub-10 nm high-K gate dielectrics on top-gated MoS2 transistors without surface functionalization

NASA Astrophysics Data System (ADS)

Lin, Yu-Shu; Cheng, Po-Hsien; Huang, Kuei-Wen; Lin, Hsin-Chih; Chen, Miin-Jang

2018-06-01

Sub-10 nm high-K gate dielectrics are of critical importance in two-dimensional transition metal dichalcogenides (TMDs) transistors. However, the chemical inertness of TMDs gives rise to a lot of pinholes in gate dielectrics, resulting in large gate leakage current. In this study, sub-10 nm, uniform and pinhole-free Al2O3 high-K gate dielectrics on MoS2 were achieved by atomic layer deposition without surface functionalization, in which an ultrathin Al2O3 layer prepared with a short purge time at a low temperature of 80 °C offers the nucleation cites for the deposition of the overlaying oxide at a higher temperature. Conductive atomic force microscopy reveals the significant suppression of gate leakage current in the sub-10 nm Al2O3 gate dielectrics with the low-temperature nucleation layer. Raman and X-ray photoelectron spectroscopies indicate that no oxidation occurred during the deposition of the low-temperature Al2O3 nucleation layer on MoS2. With the high-quality sub-10 nm Al2O3 high-K gate dielectrics, low hysteresis and subthreshold swing were demonstrated on the normally-off top-gated MoS2 transistors.

Canceling actions involves a race between basal ganglia pathways

PubMed Central

Schmidt, Robert; Leventhal, Daniel K.; Mallet, Nicolas; Chen, Fujun; Berke, Joshua D.

2013-01-01

Salient cues can prompt the rapid interruption of planned actions. It has been proposed that fast, reactive behavioral inhibition involves specific basal ganglia pathways, and we tested this by comparing activity in multiple rat basal ganglia structures during performance of a stop-signal task. Subthalamic nucleus (STN) neurons showed low-latency responses to Stop cues, irrespective of whether actions were successfully canceled or not. By contrast, neurons downstream in the substantia nigra pars reticulata (SNr) responded to Stop cues only in trials with successful cancellation. Recordings and simulations together indicate that this sensorimotor gating arises from the relative timing of two distinct inputs to neurons in the SNr dorsolateral “core” subregion: cue-related excitation from STN and movement-related inhibition from striatum. Our results support race models of action cancellation, with successful stopping requiring Stop cue information to be transmitted from STN to SNr before increased striatal input creates a point of no return. PMID:23852117

AC-186, a Selective Nonsteroidal Estrogen Receptor β Agonist, Shows Gender Specific Neuroprotection in a Parkinson’s Disease Rat Model

PubMed Central

2013-01-01

Drugs that selectively activate estrogen receptor β (ERβ) are potentially safer than the nonselective estrogens currently used in hormonal replacement treatments that activate both ERβ and ERα. The selective ERβ agonist AC-186 was evaluated in a rat model of Parkinson’s disease induced through bilateral 6-hydroxydopamine lesions of the substantia nigra. In this model, AC-186 prevented motor, cognitive, and sensorimotor gating deficits and mitigated the loss of dopamine neurons in the substantia nigra, in males, but not in females. Furthermore, in male rats, 17β-estradiol, which activates ERβ and ERα with equal potency, did not show the same neuroprotective benefits as AC-186. Hence, in addition to a beneficial safety profile for use in both males and females, a selective ERβ agonist has a differentiated pharmacological profile compared to 17β-estradiol in males. PMID:23898966

Toxoplasma gondii strain-dependent effects on mouse behaviour.

PubMed

Kannan, Geetha; Moldovan, Krisztina; Xiao, Jian-Chun; Yolken, Robert H; Jones-Brando, Lorraine; Pletnikov, Mikhail V

2010-06-01

Toxoplasma gondii reportedly manipulates rodent behaviour to increase transmission to its definitive feline host. We compared the effects of mouse infection by two Type II strains of T. gondii, Prugniaud (PRU) and ME49, on attraction to cat odour, locomotor activity, anxiety, sensorimotor gating, and spatial working and recognition memory 2 months post-infection (mpi). Attraction to cat odour was reassessed 7 mpi. At 2 mpi, mice infected with either strain exhibited significantly more attraction to cat odour than uninfected animals did, but only PRU-infected mice exhibited this behaviour 7 mpi. PRU-infected mice had significantly greater body weights and hyperactivity, while ME49-infected mice exhibited impaired spatial working memory. No differences in parasite antibody titres were seen between PRU- and ME49-infected mice. The present data suggest the effect of T. gondii infection on mouse behaviour is parasite strain-dependent.

A risk PRODH haplotype affects sensorimotor gating, memory, schizotypy, and anxiety in healthy male subjects.

PubMed

Roussos, Panos; Giakoumaki, Stella G; Bitsios, Panos

2009-06-15

Significant associations have been shown for haplotypes comprising three PRODH single nucleotide polymorphisms (SNPs; 1945T/C, 1766A/G, 1852G/A) located in the 3' region of the gene, suggesting a role of these variants in the etiopathogenesis of schizophrenia. We assessed the relationship between these high-risk PRODH polymorphisms and schizophrenia-related endophenotypes in a large and highly homogeneous cohort of healthy males. Participants (n = 217) were tested in prepulse inhibition (PPI), verbal and working memory, trait anxiety and schizotypy. The QTPHASE from the UNPHASED package was used for the association analysis of each SNP or haplotype data. This procedure revealed significant phenotypic impact of the risk CGA haplotype. Subjects were then divided in two groups; levels of PPI, anxiety, and schizotypy, verbal and working memory were compared with analysis of variance. CGA carriers (n = 32) exhibited attenuated PPI (p < .001) and verbal memory (p < .001) and higher anxiety (p < .004) and schizotypy (p < .008) compared with the noncarriers (n = 185). There were no differences in baseline startle, demographics, and working memory. The main significant correlations were schizotypy x PPI [85-dB, 120-msec trials] in the carriers and schizotypy x anxiety in the entire group and the noncarriers but not the carriers group. Our results strongly support PPI as a valid schizophrenia endophenotype and highlight the importance of examining the role of risk haplotypes on multiple endophenotypes and have implications for understanding the continuum from normality to psychosis, transitional states, and the genetics of schizophrenia-related traits.

Disrupting Jagged1-Notch signaling impairs spatial memory formation in adult mice.

PubMed

Sargin, Derya; Botly, Leigh C P; Higgs, Gemma; Marsolais, Alexander; Frankland, Paul W; Egan, Sean E; Josselyn, Sheena A

2013-07-01

It is well-known that Notch signaling plays a critical role in brain development and growing evidence implicates this signaling pathway in adult synaptic plasticity and memory formation. The Notch1 receptor is activated by two subclasses of ligands, Delta-like (including Dll1 and Dll4) and Jagged (including Jag1 and Jag2). Ligand-induced Notch1 receptor signaling is modulated by a family of Fringe proteins, including Lunatic fringe (Lfng). Although Dll1, Jag1 and Lfng are critical regulators of Notch signaling, their relative contribution to memory formation in the adult brain is unknown. To investigate the roles of these important components of Notch signaling in memory formation, we examined spatial and fear memory formation in adult mice with reduced expression of Dll1, Jag1, Lfng and Dll1 plus Lfng. We also examined motor activity, anxiety-like behavior and sensorimotor gating using the acoustic startle response in these mice. Of the lines of mutant mice tested, we found that only mice with reduced Jag1 expression (mice heterozygous for a null mutation in Jag1, Jag1(+/-)) showed a selective impairment in spatial memory formation. Importantly, all other behavior including open field activity, conditioned fear memory (both context and discrete cue), acoustic startle response and prepulse inhibition, was normal in this line of mice. These results provide the first in vivo evidence that Jag1-Notch signaling is critical for memory formation in the adult brain. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Comparison of gating methods for the real-time analysis of left ventricular function in nonimaging blood pool studies.

PubMed

Beard, B B; Stewart, J R; Shiavi, R G; Lorenz, C H

1995-01-01

Gating methods developed for electrocardiographic-triggered radionuclide ventriculography are being used with nonimaging detectors. These methods have not been compared on the basis of their real-time performance or suitability for determination of load-independent indexes of left ventricular function. This work evaluated the relative merits of different gating methods for nonimaging radionuclude ventriculographic studies, with particular emphasis on their suitability for real-time measurements and the determination of pressure-volume loops. A computer model was used to investigate the relative accuracy of forward gating, backward gating, and phase-mode gating. The durations of simulated left ventricular time-activity curves were randomly varied. Three acquisition parameters were considered: frame rate, acceptance window, and sample size. Twenty-five studies were performed for each combination of acquisition parameters. Hemodynamic and shape parameters from each study were compared with reference parameters derived directly from the random time-activity curves. Backward gating produced the largest errors under all conditions. For both forward gating and phase-mode gating, ejection fraction was underestimated and time to end systole and normalized peak ejection rate were overestimated. For the hemodynamic parameters, forward gating was marginally superior to phase-mode gating. The mean difference in errors between forward and phase-mode gating was 1.47% (SD 2.78%). However, for root mean square shape error, forward gating was several times worse in every case and seven times worse than phase-mode gating on average. Both forward and phase-mode gating are suitable for real-time hemodynamic measurements by nonimaging techniques. The small statistical difference between the methods is not clinically significant. The true shape of the time-activity curve is maintained most accurately by phase-mode gating.

Comparison of gating methods for the real-time analysis of left ventricular function in nonimaging blood pool studies

PubMed Central

Beard, Brian B.; Stewart, James R.; Shiavi, Richard G.; Lorenz, Christine H.

2018-01-01

Background Gating methods developed for electrocardiographic-triggered radionuclide ventriculography are being used with nonimaging detectors. These methods have not been compared on the basis of their real-time performance or suitability for determination of load-independent indexes of left ventricular function. This work evaluated the relative merits of different gating methods for nonimaging radionuclude ventriculographic studies, with particular emphasis on their suitability for real-time measurements and the determination of pressure-volume loops. Methods and Results A computer model was used to investigate the relative accuracy of forward gating, backward gating, and phase-mode gating. The durations of simulated left ventricular time-activity curves were randomly varied. Three acquisition parameters were considered: frame rate, acceptance window, and sample size. Twenty-five studies were performed for each combination of acquisition parameters. Hemodynamic and shape parameters from each study were compared with reference parameters derived directly from the random time-activity curves. Backward gating produced the largest errors under all conditions. For both forward gating and phase-mode gating, ejection fraction was underestimated and time to end systole and normalized peak ejection rate were overestimated. For the hemodynamic parameters, forward gating was marginally superior to phase-mode gating. The mean difference in errors between forward and phase-mode gating was 1.47% (SD 2.78%). However, for root mean square shape error, forward gating was several times worse in every case and seven times worse than phase-mode gating on average. Conclusions Both forward and phase-mode gating are suitable for real-time hemodynamic measurements by nonimaging techniques. The small statistical difference between the methods is not clinically significant. The true shape of the time-activity curve is maintained most accurately by phase-mode gating. PMID:9420820

Gated-SPECT myocardial perfusion imaging as a complementary technique to magnetic resonance imaging in chronic myocardial infarction patients.

PubMed

Cuberas-Borrós, Gemma; Pineda, Victor; Aguadé-Bruix, Santiago; Romero-Farina, Guillermo; Pizzi, M Nazarena; de León, Gustavo; Castell-Conesa, Joan; García-Dorado, David; Candell-Riera, Jaume

2013-09-01

The aim of this study was to compare magnetic resonance and gated-SPECT myocardial perfusion imaging in patients with chronic myocardial infarction. Magnetic resonance imaging and gated-SPECT were performed in 104 patients (mean age, 61 [12] years; 87.5% male) with a previous infarction. Left ventricular volumes and ejection fraction and classic late gadolinium enhancement viability criteria (<75% transmurality) were correlated with those of gated-SPECT (uptake >50%) in the 17 segments of the left ventricle. Motion, thickening, and ischemia on SPECT were analyzed in segments showing nonviable tissue or equivocal enhancement features (50%-75% transmurality). A good correlation was observed between the 2 techniques for volumes, ejection fraction (P<.05), and estimated necrotic mass (P<.01). In total, 82 of 264 segments (31%) with >75% enhancement had >50% single SPECT uptake. Of the 106 equivocal segments on magnetic resonance imaging, 68 (64%) had >50% uptake, 41 (38.7%) had normal motion, 46 (43.4%) had normal thickening, and 17 (16%) had ischemic criteria on SPECT. A third of nonviable segments on magnetic resonance imaging showed >50% uptake on SPECT. Gated-SPECT can be useful in the analysis of motion, thickening, and ischemic criteria in segments with questionable viability on magnetic resonance imaging. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Cognitive-behavioral therapy induces sensorimotor and specific electrocortical changes in chronic tic and Tourette's disorder.

PubMed

Morand-Beaulieu, Simon; O'Connor, Kieron P; Sauvé, Geneviève; Blanchet, Pierre J; Lavoie, Marc E

2015-12-01

Tic disorders, such as the Gilles de la Tourette syndrome and persistent tic disorder, are neurodevelopmental movement disorders involving impaired motor control. Hence, patients show repetitive unwanted muscular contractions in one or more parts of the body. A cognitive-behavioral therapy, with a particular emphasis on the psychophysiology of tic expression and sensorimotor activation, can reduce the frequency and intensity of tics. However, its impact on motor activation and inhibition is not fully understood. To study the effects of a cognitive-behavioral therapy on electrocortical activation, we recorded the event-related potentials (ERP) and lateralized readiness potentials (LRP), before and after treatment, of 20 patients with tic disorders and 20 healthy control participants (matched on age, sex and intelligence), during a stimulus-response compatibility inhibition task. The cognitive-behavioral therapy included informational, awareness training, relaxation, muscle discrimination, cognitive restructuration and relapse prevention strategies. Our results revealed that prior to treatment; tic patients had delayed stimulus-locked LRP onset latency, larger response-locked LRP peak amplitude, and a frontal overactivation during stimulus inhibition processing. Both stimulus-locked LRP onset latency and response-locked LRP peak amplitude normalized after the cognitive behavioral therapy completion. However, the frontal overactivation related to inhibition remained unchanged following therapy. Our results showed that P300 and reaction times are sensitive to stimulus-response compatibility, but are not related to tic symptoms. Secondly, overactivity of the frontal LPC and impulsivity in TD patients were not affected by treatment. Finally, CBT had normalizing effects on the activation of the pre-motor and motor cortex in TD patients. These results imply specific modifications of motor processes following therapy, while inhibition processes remained unchanged. Given that LRPs are partially generated within the sensorimotor and supplementary motor area, the reported reduction in tic frequency and improvements of LRPs components suggest that CBT induced a physiological change in patients' motor area. Copyright © 2015 Elsevier Ltd. All rights reserved.

A conserved tripeptide in CNG and HCN channels regulates ligand gating by controlling C-terminal oligomerization.

PubMed

Zhou, Lei; Olivier, Nelson B; Yao, Huan; Young, Edgar C; Siegelbaum, Steven A

2004-12-02

Cyclic nucleotides directly enhance the opening of the tetrameric CNG and HCN channels, although the mechanism remains unclear. We examined why HCN and certain CNG subunits form functional homomeric channels, whereas other CNG subunits only function in heteromeric channels. The "defect" in the CNGA4 subunit that prevents its homomeric expression was localized to its C-linker, which connects the transmembrane domain to the binding domain and contains a tripeptide that decreases the efficacy of ligand gating. Remarkably, replacement of the homologous HCN tripeptide with the CNGA4 sequence transformed cAMP into an inverse agonist that inhibits HCN channel opening. Using analytical ultracentrifugation, we identified the structural basis for this gating switch: whereas cAMP normally enhances the assembly of HCN C-terminal domains into a tetrameric gating ring, inclusion of the CNGA4 tripeptide reversed this action so that cAMP now causes gating ring disassembly. Thus, ligand gating depends on the dynamic oligomerization of C-terminal binding domains.

Localized normalization for improved calibration curves of manganese and zinc in laser-induced plasma spectroscopy

NASA Astrophysics Data System (ADS)

Sabri, Nursalwanie Mohd; Haider, Zuhaib; Tufail, Kashif; Imran, Muhammad; Ali, Jalil

2017-03-01

Laser-induced plasma spectroscopy is performed to determine the elemental compositions of manganese and zinc in potassium bromide (KBr) matrix. This work has utilized Q-switched Nd:YAG laser installed in LIBS2500plus system at fundamental wavelength. The pelletized sample were ablated in air with maximum laser energy of 650 mJ for different gate delays ranging from 0-18 µs. The spectra of samples are obtained for five different compositions containing preferred spectral lines. The intensity of spectral line is observed at its maximum at a gate-delay 0.83 µs and subsequently decayed exponentially with the increasing of gate delay. Maximum signal-to-background ratio of Mn and Zn were found at gate delays of 7.92 and 7.50 µs, respectively. Initial calibration curves show bad data fitting, whereas the locally normalized intensity for both spectral lines shows enhancement since it is more linearly regressed. This study will give a better understanding in studying the plasma emission and the spectra analysis. At the request of all authors of the paper, and with the agreement of the Proceedings Editor, an updated version of this article was published on 24 May 2017.

Tourette syndrome: the self under siege.

PubMed

Leckman, James F; Bloch, Michael H; Scahill, Lawrence; King, Robert A

2006-08-01

Tourette syndrome is a neurodevelopmental disorder characterized by motor and vocal tics--rapid, repetitive, stereotyped movements or vocalizations. Tourette syndrome typically has a prepubertal onset, and boys are more commonly affected than girls. Symptoms usually begin with transient bouts of simple motor tics. By age 10 years, most children are aware of nearly irresistible somatosensory urges that precede the tics. These urges likely reflect a defect in sensorimotor gating because they intrude into the child's conscious awareness and become a source of distraction and distress. A momentary sense of relief typically follows the completion of a tic. Over the course of hours, tics occur in bouts, with a regular intertic interval. Tics increase during periods of emotional excitement and fatigue. Tics can become "complex" in nature and appear to be purposeful. Tics can be willfully suppressed for brief intervals and can be evoked by the mere mention of them. Tics typically diminish during periods of goal-directed behavior, especially those that involve both heightened attention and fine motor or vocal control, as occur in musical and athletic performances. Over the course of months, tics wax and wane. New tics appear, often in response to new sources of somatosensory irritation, such as the appearance of a persistent vocal tic (a cough) following a cold. Over the course of years, tic severity typically peaks between 8 and 12 years of age. By the end of the second decade of life, many individuals are virtually tic free. Less than 20% of cases continue to experience clinically impairing tics as adults. Tics rarely occur in isolation, and other coexisting conditions--such as behavioral disinhibition, hypersensitivity to a broad range of sensory stimuli, problems with visual motor integration, procedural learning difficulties, attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder, depression, anxiety, and emotional instability--are often a greater source of impairment than the tics themselves. Emerging behavioral treatments of Tourette syndrome are based in part on an understanding of the moment-to-moment experience of somatosensory urges and motor response. With identification of specific genes of major effect and advances in our understanding of the neural circuitry of sensorimotor gating, habit formation, and procedural memory--together with insights from postmortem brain studies, in vivo brain imaging, and electrophysiologic recordings--we might be on the threshold of a deeper understanding of the phenomenology and natural history of Tourette syndrome.

Behavioral, Neurophysiological, and Synaptic Impairment in a Transgenic Neuregulin1 (NRG1-IV) Murine Schizophrenia Model

PubMed Central

Papaleo, Francesco; Yang, Feng; Paterson, Clare; Palumbo, Sara; Carr, Gregory V.; Wang, Yanhong; Floyd, Kirsten; Huang, Wenwei; Thomas, Craig J.; Chen, Jingshan; Weinberger, Daniel R.

2016-01-01

Schizophrenia is a chronic, disabling neuropsychiatric disorder with complex genetic origins. The development of strategies for genome manipulation in rodents provides a platform for understanding the pathogenic role of genes and for testing novel therapeutic agents. Neuregulin 1 (NRG1), a critical developmental neurotrophin, is associated with schizophrenia. The NRG1 gene undergoes extensive alternative splicing and, to date, little is known about the neurobiology of a novel NRG1 isoform, NRG1-IV, which is increased in the brains of individuals with schizophrenia and associated with genetic risk variation. Here, we developed a transgenic mouse model (NRG1-IV/NSE-tTA) in which human NRG1-IV is selectively overexpressed in a neuronal specific manner. Using a combination of molecular, biochemical, electrophysiological, and behavioral analyses, we demonstrate that NRG1-IV/NSE-tTA mice exhibit abnormal behaviors relevant to schizophrenia, including impaired sensorimotor gating, discrimination memory, and social behaviors. These neurobehavioral phenotypes are accompanied by increases in cortical expression of the NRG1 receptor, ErbB4 and the downstream signaling target, PIK3-p110δ, along with disrupted dendritic development, synaptic pathology, and altered prefrontal cortical excitatory–inhibitory balance. Pharmacological inhibition of p110δ reversed sensorimotor gating and cognitive deficits. These data demonstrate a novel role for NRG1-IV in learning, memory, and neural circuit formation and a potential neurobiological mechanism for schizophrenia risk; show that deficits are pharmacologically reversible in adulthood; and further highlight p110δ as a target for antipsychotic drug development. SIGNIFICANCE STATEMENT Schizophrenia is a disabling psychiatric disorder with neurodevelopmental origins. Genes that increase risk for schizophrenia have been identified. Understanding how these genes affect brain development and function is necessary. This work is the first report of a newly generated humanized transgenic mouse model engineered to express human NRG1-IV, an isoform of the NRG1 (Neuregulin 1) gene that is increased in the brains of patients with schizophrenia in association with genetic risk. Using behavioral neuroscience, molecular biology, electrophysiology, and pharmacology, we identify a role for NRG1-IV in learning, memory, and cognition and determine that this relates to brain excitatory–inhibitory balance and changes in ErbB4/PI3K/AKT signaling. Moreover, the study further highlights the potential of targeting the PI3K pathway for the treatment of schizophrenia. PMID:27122041

Analyzing the experiences of adolescent control rats: Effects of the absence of physical or social stimulation on anxiety-like behaviour are dependent on the test.

PubMed

Joshi, Namrata; Leslie, Ronald A; Perrot, Tara S

2017-10-01

The present study was designed to systematically assess the control experience routinely used in our laboratory as part of studies on predator odour stress. Specifically, we examined effects of the physical and social components of this control experience on measures of anxiety-like behaviour in adolescent rats. Adolescent animals are at increased susceptibility to environmental perturbations and have been used for such studies much less often. Long-Evans rats of both sexes were subjected to physical stimulation (Exposed or Unexposed) and social stimulation (Single-Housed or Pair-Housed), resulting in four groups. Exposed rats received six 30-min exposures to an enclosed arena containing an unscented piece of cat collar occurring between adolescence and early adulthood, while Unexposed remained in the home cage. Groups of Exposed and Unexposed animals were housed singly (Single-Housed) from early adolescence to early adulthood or Pair-Housed during this time. Experimental procedures began in adolescence and involved repeated assessment of startle amplitude (measure of anxiety-like behaviour) and prepulse inhibition (PPI; a measure of sensorimotor gating) to gauge the short-term impact of social and/or physical stimulation. All animals were re-paired in adulthood prior to a final startle/PPI session to assess if isolation limited to adolescence could impose long-term effects that were not reversible. We also measured anxiety-like behaviour in adulthood using an extended open field test (EOFT; addition of novel objects to the open field on later days), and the elevated plus maze task (EPM), as well as a sucrose preference test (SPT) to measure anhedonia. An absence of social or physical stimulation resulted in increased startle amplitude and some measures of anxiety-like behaviour in the EOFT, but a reduction in such anxiety-like behaviour in the EPM task. These results suggest common neural substrates for the physical and social experiences. Performance in the SPT was unaltered by any experimental treatments. Sensorimotor gating, as measured by PPI, was increased in the absence of physical stimulation with no short-term effect of isolation, or of re-pairing. These results indicate the importance of considering individual components of the rearing environment of rats, while showing the need to use multiple assays of anxiety-like behaviour. Copyright © 2017. Published by Elsevier Inc.

Neuroprosthetics and Solutions for Restoring Sensorimotor Functions

DTIC Science & Technology

2009-01-01

in the stab wound control (A, C) and the 1-week implantation of the electrode (B, D). Striking neurofilament loss occurred surrounding both the stab...force. (Like in heel strike and toe of in normal gait cycle). (B) The Proof Test is a static test for foot ankle unit in which maximum load is...applied on heel and forefoot in one single time successively. Project 1. Develop a somatosensory neural interface (SSNI) -Completed pilot testing of

Electrical Stimulation of the Midbrain to Promote Recovery from Traumatic Forebrain Injury

DTIC Science & Technology

2009-04-01

the beneficial trophic effects . The cylinder test, taken to indicate somatosensory function, gave highly variable results. We were unable to see a...learning in a hidden-platform water maze test was speeded by both dorsal and median raphe stimulation. Rearing movements in a transparent cylinder ...sensorimotor performance) were normalized by the median but not the dorsal raphe. One adverse effect was seen: the dorsal but not the median raphe reduced

Sensorimotor integration in human postural control

NASA Technical Reports Server (NTRS)

Peterka, R. J.

2002-01-01

It is generally accepted that human bipedal upright stance is achieved by feedback mechanisms that generate an appropriate corrective torque based on body-sway motion detected primarily by visual, vestibular, and proprioceptive sensory systems. Because orientation information from the various senses is not always available (eyes closed) or accurate (compliant support surface), the postural control system must somehow adjust to maintain stance in a wide variety of environmental conditions. This is the sensorimotor integration problem that we investigated by evoking anterior-posterior (AP) body sway using pseudorandom rotation of the visual surround and/or support surface (amplitudes 0.5-8 degrees ) in both normal subjects and subjects with severe bilateral vestibular loss (VL). AP rotation of body center-of-mass (COM) was measured in response to six conditions offering different combinations of available sensory information. Stimulus-response data were analyzed using spectral analysis to compute transfer functions and coherence functions over a frequency range from 0.017 to 2.23 Hz. Stimulus-response data were quite linear for any given condition and amplitude. However, overall behavior in normal subjects was nonlinear because gain decreased and phase functions sometimes changed with increasing stimulus amplitude. "Sensory channel reweighting" could account for this nonlinear behavior with subjects showing increasing reliance on vestibular cues as stimulus amplitudes increased. VL subjects could not perform this reweighting, and their stimulus-response behavior remained quite linear. Transfer function curve fits based on a simple feedback control model provided estimates of postural stiffness, damping, and feedback time delay. There were only small changes in these parameters with increasing visual stimulus amplitude. However, stiffness increased as much as 60% with increasing support surface amplitude. To maintain postural stability and avoid resonant behavior, an increase in stiffness should be accompanied by a corresponding increase in damping. Increased damping was achieved primarily by decreasing the apparent time delay of feedback control rather than by changing the damping coefficient (i.e., corrective torque related to body-sway velocity). In normal subjects, stiffness and damping were highly correlated with body mass and moment of inertia, with stiffness always about 1/3 larger than necessary to resist the destabilizing torque due to gravity. The stiffness parameter in some VL subjects was larger compared with normal subjects, suggesting that they may use increased stiffness to help compensate for their loss. Overall results show that the simple act of standing quietly depends on a remarkably complex sensorimotor control system.

Voltage gating of mechanosensitive PIEZO channels.

PubMed

Moroni, Mirko; Servin-Vences, M Rocio; Fleischer, Raluca; Sánchez-Carranza, Oscar; Lewin, Gary R

2018-03-15

Mechanosensitive PIEZO ion channels are evolutionarily conserved proteins whose presence is critical for normal physiology in multicellular organisms. Here we show that, in addition to mechanical stimuli, PIEZO channels are also powerfully modulated by voltage and can even switch to a purely voltage-gated mode. Mutations that cause human diseases, such as xerocytosis, profoundly shift voltage sensitivity of PIEZO1 channels toward the resting membrane potential and strongly promote voltage gating. Voltage modulation may be explained by the presence of an inactivation gate in the pore, the opening of which is promoted by outward permeation. Older invertebrate (fly) and vertebrate (fish) PIEZO proteins are also voltage sensitive, but voltage gating is a much more prominent feature of these older channels. We propose that the voltage sensitivity of PIEZO channels is a deep property co-opted to add a regulatory mechanism for PIEZO activation in widely different cellular contexts.

Remodeling of Sensorimotor Brain Connectivity in Gpr88-Deficient Mice.

PubMed

Arefin, Tanzil Mahmud; Mechling, Anna E; Meirsman, Aura Carole; Bienert, Thomas; Hübner, Neele Saskia; Lee, Hsu-Lei; Ben Hamida, Sami; Ehrlich, Aliza; Roquet, Dan; Hennig, Jürgen; von Elverfeldt, Dominik; Kieffer, Brigitte Lina; Harsan, Laura-Adela

2017-10-01

Recent studies have demonstrated that orchestrated gene activity and expression support synchronous activity of brain networks. However, there is a paucity of information on the consequences of single gene function on overall brain functional organization and connectivity and how this translates at the behavioral level. In this study, we combined mouse mutagenesis with functional and structural magnetic resonance imaging (MRI) to determine whether targeted inactivation of a single gene would modify whole-brain connectivity in live animals. The targeted gene encodes GPR88 (G protein-coupled receptor 88), an orphan G protein-coupled receptor enriched in the striatum and previously linked to behavioral traits relevant to neuropsychiatric disorders. Connectivity analysis of Gpr88-deficient mice revealed extensive remodeling of intracortical and cortico-subcortical networks. Most prominent modifications were observed at the level of retrosplenial cortex connectivity, central to the default mode network (DMN) whose alteration is considered a hallmark of many psychiatric conditions. Next, somatosensory and motor cortical networks were most affected. These modifications directly relate to sensorimotor gating deficiency reported in mutant animals and also likely underlie their hyperactivity phenotype. Finally, we identified alterations within hippocampal and dorsal striatum functional connectivity, most relevant to a specific learning deficit that we previously reported in Gpr88 -/- animals. In addition, amygdala connectivity with cortex and striatum was weakened, perhaps underlying the risk-taking behavior of these animals. This is the first evidence demonstrating that GPR88 activity shapes the mouse brain functional and structural connectome. The concordance between connectivity alterations and behavior deficits observed in Gpr88-deficient mice suggests a role for GPR88 in brain communication.

Too Little and Too Much: Hypoactivation and Disinhibition of Medial Prefrontal Cortex Cause Attentional Deficits

PubMed Central

McGarrity, Stephanie; Mason, Rob; Fone, Kevin C.

2014-01-01

Attentional deficits are core symptoms of schizophrenia, contributing strongly to disability. Prefrontal dysfunction has emerged as a candidate mechanism, with clinical evidence for prefrontal hypoactivation and disinhibition (reduced GABAergic inhibition), possibly reflecting different patient subpopulations. Here, we tested in rats whether imbalanced prefrontal neural activity impairs attention. To induce prefrontal hypoactivation or disinhibition, we microinfused the GABA-A receptor agonist muscimol (C4H6N2O2; 62.5, 125, 250 ng/side) or antagonist picrotoxin (C30H34O13; 75, 150, 300 ng/side), respectively, into the medial prefrontal cortex. Using the five-choice serial reaction time (5CSRT) test, we showed that both muscimol and picrotoxin impaired attention (reduced accuracy, increased omissions). Muscimol also impaired response control (increased premature responses). In addition, muscimol dose dependently reduced open-field locomotor activity, whereas 300 ng of picrotoxin caused locomotor hyperactivity; sensorimotor gating (startle prepulse inhibition) was unaffected. Therefore, infusion effects on the 5CSRT test can be dissociated from sensorimotor effects. Combining microinfusions with in vivo electrophysiology, we showed that muscimol inhibited prefrontal firing, whereas picrotoxin increased firing, mainly within bursts. Muscimol reduced and picrotoxin enhanced bursting and both drugs changed the temporal pattern of bursting. Picrotoxin also markedly enhanced prefrontal LFP power. Therefore, prefrontal hypoactivation and disinhibition both cause attentional deficits. Considering the electrophysiological findings, this suggests that attention requires appropriately tuned prefrontal activity. Apart from attentional deficits, prefrontal disinhibition caused additional neurobehavioral changes that may be relevant to schizophrenia pathophysiology, including enhanced prefrontal bursting and locomotor hyperactivity, which have been linked to psychosis-related dopamine hyperfunction. PMID:24899715

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

PubMed

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

2013-08-01

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

Effects of memantine on hippocampal long-term potentiation, gamma activity, and sensorimotor gating in freely moving rats.

PubMed

Ma, Jingyi; Mufti, Asfandyar; Stan Leung, L

2015-09-01

Memantine, an uncompetitive N-methyl-D-aspartate receptor antagonist, is used for treatment of patients with Alzheimer's disease. The mechanisms of memantine in relieving cognitive and behavioral symptoms are unclear, and this study attempts to elucidate its action on network and synaptic functions of the hippocampus. The effects of memantine on electrographic activity and hippocampal long-term potentiation (LTP) were investigated in freely moving rats. Basal dendritic excitation on hippocampal CA1 pyramidal cells showed a robust LTP after theta-frequency primed bursts, and the LTP was higher after 5-10 mg/kg intraperitoneal (ip) memantine pretreatment, as compared with saline pretreatment. Injection of scopolamine (5 mg/kg ip) before memantine failed to block the LTP-enhancing effect of memantine. Memantine as compared with saline pretreatment did not affect the LTP after an afterdischarge induced by high-frequency (200-Hz) train stimulation. Memantine (5 or 10 mg/kg ip) significantly enhanced gamma oscillations in the hippocampal local field potentials of 40-100 Hz during walking and awake immobility. Memantine at 10 mg/kg ip, but not at 5 mg/kg ip, increased prepulse inhibition of the acoustic startle response, while both 5 and 10 mg/kg ip memantine enhanced the acoustic startle response as compared with saline-injected rats. These electrophysiological and behavioral effects of memantine are unique among N-methyl-D-aspartate receptor antagonists but are consistent with memantine's effects in improving cognitive and sensorimotor functions of Alzheimer's patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Histidine168 is crucial for ΔpH-dependent gating of the human voltage-gated proton channel, hHV1.

PubMed

Cherny, Vladimir V; Morgan, Deri; Thomas, Sarah; Smith, Susan M E; DeCoursey, Thomas E

2018-05-09

We recently identified a voltage-gated proton channel gene in the snail Helisoma trivolvis , HtH V 1, and determined its electrophysiological properties. Consistent with early studies of proton currents in snail neurons, HtH V 1 opens rapidly, but it unexpectedly exhibits uniquely defective sensitivity to intracellular pH (pH i ). The H + conductance ( g H )- V relationship in the voltage-gated proton channel (H V 1) from other species shifts 40 mV when either pH i or pH o (extracellular pH) is changed by 1 unit. This property, called ΔpH-dependent gating, is crucial to the functions of H V 1 in many species and in numerous human tissues. The HtH V 1 channel exhibits normal pH o dependence but anomalously weak pH i dependence. In this study, we show that a single point mutation in human hH V 1-changing His 168 to Gln 168 , the corresponding residue in HtH V 1-compromises the pH i dependence of gating in the human channel so that it recapitulates the HtH V 1 response. This location was previously identified as a contributor to the rapid gating kinetics of H V 1 in Strongylocentrotus purpuratus His 168 mutation in human H V 1 accelerates activation but accounts for only a fraction of the species difference. H168Q, H168S, or H168T mutants exhibit normal pH o dependence, but changing pH i shifts the g H - V relationship on average by <20 mV/unit. Thus, His 168 is critical to pH i sensing in hH V 1. His 168 , located at the inner end of the pore on the S3 transmembrane helix, is the first residue identified in H V 1 that significantly impairs pH sensing when mutated. Because pH o dependence remains intact, the selective erosion of pH i dependence supports the idea that there are distinct internal and external pH sensors. Although His 168 may itself be a pH i sensor, the converse mutation, Q229H, does not normalize the pH i sensitivity of the HtH V 1 channel. We hypothesize that the imidazole group of His 168 interacts with nearby Phe 165 or other parts of hH V 1 to transduce pH i into shifts of voltage-dependent gating. © 2018 Cherny et al.

Silicon on insulator self-aligned transistors

DOEpatents

McCarthy, Anthony M.

2003-11-18

A method for fabricating thin-film single-crystal silicon-on-insulator (SOI) self-aligned transistors. Standard processing of silicon substrates is used to fabricate the transistors. Physical spaces, between the source and gate, and the drain and gate, introduced by etching the polysilicon gate material, are used to provide connecting implants (bridges) which allow the transistor to perform normally. After completion of the silicon substrate processing, the silicon wafer is bonded to an insulator (glass) substrate, and the silicon substrate is removed leaving the transistors on the insulator (glass) substrate. Transistors fabricated by this method may be utilized, for example, in flat panel displays, etc.

Improving Sensorimotor Function and Adaptation using Stochastic Vestibular Stimulation

NASA Technical Reports Server (NTRS)

Galvan, R. C.; Bloomberg, J. J.; Mulavara, A. P.; Clark, T. K.; Merfeld, D. M.; Oman, C. M.

2014-01-01

Astronauts experience sensorimotor changes during adaption to G-transitions that occur when entering and exiting microgravity. Post space flight, these sensorimotor disturbances can include postural and gait instability, visual performance changes, manual control disruptions, spatial disorientation, and motion sickness, all of which can hinder the operational capabilities of the astronauts. Crewmember safety would be significantly increased if sensorimotor changes brought on by gravitational changes could be mitigated and adaptation could be facilitated. The goal of this research is to investigate and develop the use of electrical stochastic vestibular stimulation (SVS) as a countermeasure to augment sensorimotor function and facilitate adaptation. For this project, SVS will be applied via electrodes on the mastoid processes at imperceptible amplitude levels. We hypothesize that SVS will improve sensorimotor performance through the phenomena of stochastic resonance, which occurs when the response of a nonlinear system to a weak input signal is optimized by the application of a particular nonzero level of noise. In line with the theory of stochastic resonance, a specific optimal level of SVS will be found and tested for each subject [1]. Three experiments are planned to investigate the use of SVS in sensory-dependent tasks and performance. The first experiment will aim to demonstrate stochastic resonance in the vestibular system through perception based motion recognition thresholds obtained using a 6-degree of freedom Stewart platform in the Jenks Vestibular Laboratory at Massachusetts Eye and Ear Infirmary. A range of SVS amplitudes will be applied to each subject and the subjectspecific optimal SVS level will be identified as that which results in the lowest motion recognition threshold, through previously established, well developed methods [2,3,4]. The second experiment will investigate the use of optimal SVS in facilitating sensorimotor adaptation to system disturbances. Subjects will adapt to wearing minifying glasses, resulting in decreased vestibular ocular reflex (VOR) gain. The VOR gain will then be intermittently measured while the subject readapts to normal vision, with and without optimal SVS. We expect that optimal SVS will cause a steepening of the adaptation curve. The third experiment will test the use of optimal SVS in an operationally relevant aerospace task, using the tilt translation sled at NASA Johnson Space Center, a test platform capable of recreating the tilt-gain and tilt-translation illusions associated with landing of a spacecraft post-space flight. In this experiment, a perception based manual control measure will be used to compare performance with and without optimal SVS. We expect performance to improve in this task when optimal SVS is applied. The ultimate goal of this work is to systematically investigate and further understand the potential benefits of stochastic vestibular stimulation in the context of human space flight so that it may be used in the future as a component of a comprehensive countermeasure plan for adaptation to G-transitions.

Cluster State Quantum Computing

DTIC Science & Technology

2012-12-01

probability that the desired target gate ATar has been faithfully implemented on the computational modes given a successful measurement of the ancilla...modes: () = �(†)� 2 2(†) , (3) since Tr ( ATar † ATar )=2Mc for a properly normalized target gate. As we are interested...optimization method we have developed maximizes the success probability S for a given target transformation ATar , for given ancilla resources, and for a

Cluster State Quantum Computation

DTIC Science & Technology

2014-02-01

information of relevance to the transformation. We define the fidelity as the probability that the desired target gate ATar has been faithfully...implemented on the computational modes given a successful measurement of the ancilla modes: 2 , (3) since Tr ( ATar † ATar )=2Mc for a properly normalized...photonic gates The optimization method we have developed maximizes the success probability S for a given target transformation ATar , for given

Reference ranges for LVEF and LV volumes from electrocardiographically gated 82Rb cardiac PET/CT using commercially available software.

PubMed

Bravo, Paco E; Chien, David; Javadi, Mehrbod; Merrill, Jennifer; Bengel, Frank M

2010-06-01

Electrocardiographic gating is increasingly used for (82)Rb cardiac PET/CT, but reference ranges for global functional parameters are not well defined. We sought to establish reference values for left ventricular ejection fraction (LVEF), end systolic volume (ESV), and end diastolic volume (EDV) using 4 different commercial software packages. Additionally, we compared 2 different approaches for the definition of a healthy individual. Sixty-two subjects (mean age +/- SD, 49 +/- 9 y; 85% women; mean body mass index +/- SD, 34 +/- 10 kg/m(2)) who underwent (82)Rb-gated myocardial perfusion PET/CT were evaluated. All subjects had normal myocardial perfusion and no history of coronary artery disease (CAD) or cardiomyopathy. Subgroup 1 consisted of 34 individuals with low pretest probability of CAD (<10%), and subgroup 2 comprised 28 subjects who had no atherosclerosis on a coronary CT angiogram obtained concurrently during the PET/CT session. LVEF, ESV, and EDV were calculated at rest and during dipyridamole-induced stress, using CardIQ Physio (a dedicated PET software) and the 3 major SPECT software packages (Emory Cardiac Toolbox, Quantitative Gated SPECT, and 4DM-SPECT). Mean LVEF was significantly different among all 4 software packages. LVEF was most comparable between CardIQ Physio (62% +/- 6% and 54% +/- 7% at stress and rest, respectively) and 4DM-SPECT (64% +/- 7% and 56% +/- 8%, respectively), whereas Emory Cardiac Toolbox yielded higher values (71% +/- 6% and 65% +/- 6%, respectively, P < 0.001) and Quantitated Gated SPECT lower values (56% +/- 8% and 50% +/- 8%, respectively, P < 0.001). Subgroup 1 (low likelihood) demonstrated higher LVEF values than did subgroup 2 (normal CT angiography findings), using all software packages (P < 0.05). However, mean ESV and EDV at stress and rest were comparable between both subgroups (p = NS). Intra- and interobserver agreement were excellent for all methods. The reference range of LVEF and LV volumes from gated (82)Rb PET/CT varies significantly among available software programs and therefore cannot be used interchangeably. LVEF results were higher when healthy subjects were defined by a low pretest probability of CAD than by normal CT angiography results.

Rescue of protein expression defects may not be enough to abolish the pro-arrhythmic phenotype of long QT type 2 mutations.

PubMed

Perry, Matthew D; Ng, Chai Ann; Phan, Kevin; David, Erikka; Steer, Kieran; Hunter, Mark J; Mann, Stefan A; Imtiaz, Mohammad; Hill, Adam P; Ke, Ying; Vandenberg, Jamie I

2016-07-15

Most missense long QT syndrome type 2 (LQTS2) mutations result in Kv11.1 channels that show reduced levels of membrane expression. Pharmacological chaperones that rescue mutant channel expression could have therapeutic potential to reduce the risk of LQTS2-associated arrhythmias and sudden cardiac death, but only if the mutant Kv11.1 channels function normally (i.e. like WT channels) after membrane expression is restored. Fewer than half of mutant channels exhibit relatively normal function after rescue by low temperature. The remaining rescued missense mutant Kv11.1 channels have perturbed gating and/or ion selectivity characteristics. Co-expression of WT subunits with gating defective missense mutations ameliorates but does not eliminate the functional abnormalities observed for most mutant channels. For patients with mutations that affect gating in addition to expression, it may be necessary to use a combination therapy to restore both normal function and normal expression of the channel protein. In the heart, Kv11.1 channels pass the rapid delayed rectifier current (IKr ) which plays critical roles in repolarization of the cardiac action potential and in the suppression of arrhythmias caused by premature stimuli. Over 500 inherited mutations in Kv11.1 are known to cause long QT syndrome type 2 (LQTS2), a cardiac electrical disorder associated with an increased risk of life threatening arrhythmias. Most missense mutations in Kv11.1 reduce the amount of channel protein expressed at the membrane and, as a consequence, there has been considerable interest in developing pharmacological agents to rescue the expression of these channels. However, pharmacological chaperones will only have clinical utility if the mutant Kv11.1 channels function normally after membrane expression is restored. The aim of this study was to characterize the gating phenotype for a subset of LQTS2 mutations to assess what proportion of mutations may be suitable for rescue. As an initial screen we used reduced temperature to rescue expression defects of mutant channels expressed in Xenopus laevis oocytes. Over half (∼56%) of Kv11.1 mutants exhibited functional gating defects that either dramatically reduced the amount of current contributing to cardiac action potential repolarization and/or reduced the amount of protective current elicited in response to premature depolarizations. Our data demonstrate that if pharmacological rescue of protein expression defects is going to have clinical utility in the treatment of LQTS2 then it will be important to assess the gating phenotype of LQTS2 mutations before attempting rescue. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Kinetic gating mechanism of DNA damage recognition by Rad4/XPC

NASA Astrophysics Data System (ADS)

Chen, Xuejing; Velmurugu, Yogambigai; Zheng, Guanqun; Park, Beomseok; Shim, Yoonjung; Kim, Youngchang; Liu, Lili; van Houten, Bennett; He, Chuan; Ansari, Anjum; Min, Jung-Hyun

2015-01-01

The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair by recognizing DNA lesions before recruiting downstream factors. How XPC detects structurally diverse lesions embedded within normal DNA is unknown. Here we present a crystal structure that captures the yeast XPC orthologue (Rad4) on a single register of undamaged DNA. The structure shows that a disulphide-tethered Rad4 flips out normal nucleotides and adopts a conformation similar to that seen with damaged DNA. Contrary to many DNA repair enzymes that can directly reject non-target sites as structural misfits, our results suggest that Rad4/XPC uses a kinetic gating mechanism whereby lesion selectivity arises from the kinetic competition between DNA opening and the residence time of Rad4/XPC per site. This mechanism is further supported by measurements of Rad4-induced lesion-opening times using temperature-jump perturbation spectroscopy. Kinetic gating may be a general mechanism used by site-specific DNA-binding proteins to minimize time-consuming interrogations of non-target sites.

Multibands tunneling in AAA-stacked trilayer graphene

NASA Astrophysics Data System (ADS)

Redouani, Ilham; Jellal, Ahmed; Bahaoui, Abdelhadi; Bahlouli, Hocine

2018-04-01

We study the electronic transport through np and npn junctions for AAA-stacked trilayer graphene. Two kinds of gates are considered where the first is a single gate and the second is a double gate. After obtaining the solutions for the energy spectrum, we use the transfer matrix method to determine the three transmission probabilities for each individual cone τ = 0 , ± 1 . We show that the quasiparticles in AAA-stacked trilayer graphene are not only chiral but also labeled by an additional cone index τ. The obtained bands are composed of three Dirac cones that depend on the chirality indexes. We show that there is perfect transmission for normal or near normal incidence, which is a manifestation of the Klein tunneling effect. We analyze also the corresponding total conductance, which is defined as the sum of the conductance channels in each individual cone. Our results are numerically discussed and compared with those obtained for ABA- and ABC-stacked trilayer graphene.

Kinetic gating mechanism of DNA damage recognition by Rad4/XPC

DOE PAGES

Chen, Xuejing; Velmurugu, Yogambigai; Zheng, Guanqun; ...

2015-01-06

The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair by recognizing DNA lesions before recruiting downstream factors. How XPC detects structurally diverse lesions embedded within normal DNA is unknown. Here we present a crystal structure that captures the yeast XPC orthologue (Rad4) on a single register of undamaged DNA. The structure shows that a disulphide-tethered Rad4 flips out normal nucleotides and adopts a conformation similar to that seen with damaged DNA. Contrary to many DNA repair enzymes that can directly reject non-target sites as structural misfits, our results suggest that Rad4/XPC uses a kinetic gating mechanism whereby lesion selectivitymore » arises from the kinetic competition between DNA opening and the residence time of Rad4/XPC per site. This mechanism is further supported by measurements of Rad4-induced lesion-opening times using temperature-jump perturbation spectroscopy. Lastly, kinetic gating may be a general mechanism used by site-specific DNA-binding proteins to minimize time-consuming interrogations of non-target sites.« less

Multimodal assessment of sensorimotor shoulder function in patients with untreated anterior shoulder instability and asymptomatic handball players.

PubMed

Mornieux, Guillaume; Hirschmüller, Anja; Gollhofer, Albert; Südkamp, Norbert P; Maier, Dirk

2018-04-01

Functional evaluation of sensorimotor function of the shoulder joint is important for guidance of sports-specific training, prevention and rehabilitation of shoulder instability. Such assessment should be multimodal and comprise all qualities of sensorimotor shoulder function. This study evaluates feasibility of such multimodal assessment of glenohumeral sensorimotor function in patients with shoulder instability and handball players. Nine patients with untreated anterior instability of their dominant shoulder and 15 asymptomatic recreational handball players performed proprioceptive joint position sense and dynamic stabilization evaluations on an isokinetic device, as well as a functional throwing performance task. Outcome measures were analysed individually and equally weighted in a Shoulder-Specific Sensorimotor Index (S-SMI). Finally, isokinetic strength evaluations were conducted. We observed comparable sensorimotor functions of unstable dominant shoulders compared to healthy, contralateral shoulders (e.g. P=0.59 for S-SMI). Handball players demonstrated superior sensorimotor function of their dominant shoulders exhibiting a significantly higher throwing performance and S-SMI (P<0.001 and P=0.002, respectively), but comparable internal rotator peak torques for both shoulders (P>0.22). The present study proves feasibility of multimodal assessment of shoulder sensorimotor function in overhead athletes and patients with symptomatic anterior shoulder instability. Untreated shoulder instability led to a loss of dominance-related sensorimotor superiority indicating functional internal rotation deficiency. Dominant shoulders of handball players showed a superior overall sensorimotor function but weakness of dominant internal rotation constituting a risk factor for occurrence of posterior superior impingement syndrome. The S-SMI could serve as a diagnostic tool for guidance of sports-specific training, prevention and rehabilitation of shoulder instability.

Sensorimotor integration in chronic stroke: Baseline differences and response to sensory training.

PubMed

Brown, Katlyn E; Neva, Jason L; Feldman, Samantha J; Staines, W Richard; Boyd, Lara A

2018-01-01

The integration of somatosensory information from the environment into the motor cortex to inform movement is essential for motor function. As motor deficits commonly persist into the chronic phase of stroke recovery, it is important to understand potential contributing factors to these deficits, as well as their relationship with motor function. To date the impact of chronic stroke on sensorimotor integration has not been thoroughly investigated. The current study aimed to comprehensively examine the influence of chronic stroke on sensorimotor integration, and determine whether sensorimotor integration can be modified with an intervention. Further, it determined the relationship between neurophysiological measures of sensorimotor integration and motor deficits post-stroke. Fourteen individuals with chronic stroke and twelve older healthy controls participated. Motor impairment and function were quantified in individuals with chronic stroke. Baseline neurophysiology was assessed using nerve-based measures (short- and long-latency afferent inhibition, afferent facilitation) and vibration-based measures of sensorimotor integration, which paired vibration with single and paired-pulse TMS techniques. Neurophysiological assessment was performed before and after a vibration-based sensory training paradigm to assess changes within these circuits. Vibration-based, but not nerve-based measures of sensorimotor integration were different in individuals with chronic stroke, as compared to older healthy controls, suggesting that stroke differentially impacts integration of specific types of somatosensory information. Sensorimotor integration was behaviourally relevant in that it related to both motor function and impairment post-stroke. Finally, sensory training modulated sensorimotor integration in individuals with chronic stroke and controls. Sensorimotor integration is differentially impacted by chronic stroke based on the type of afferent feedback. However, both nerve-based and vibration-based measures relate to motor impairment and function in individuals with chronic stroke.

Static and Turn-on Switching Characteristics of 4H-Silicon Carbide SITs to 200 deg C

NASA Technical Reports Server (NTRS)

Niedra, Janis M.; Schwarze, Gene E.

2005-01-01

Test results are presented for normally-off 4H-SiC Static Induction Transistors (SITs) intended for power switching and are among the first normally-off such devices realized in SiC. At zero gate bias, the gate p-n junction depletion layers extend far enough into the conduction channel to cut off the channel. Application of forward gate bias narrows the depletion regions, opening up the channel to conduction by majority carriers. In the present devices, narrow vertical channels get pinched by depletion regions from opposite sides. Since the material is SiC, the devices are usable at temperatures above 150 C. Static curve and pulse mode switching observations were done at selected temperatures up to 200 C on a device with average static characteristics from a batch of similar devices. Gate and drain currents were limited to about 400 mA and 3.5 A, respectively. The drain voltage was limited to roughly 300 V, which is conservative for this 600 V rated device. At 23 C, 1 kW, or even more, could be pulse mode switched in 65 ns (10 to 90 percent) into a 100 load. But at 200 C, the switching capability is greatly reduced in large part by the excessive gate current required. Severe collapse of the saturated drain-to-source current was observed at 200 C. The relation of this property to channel mobility is reviewed.

2014 Sensorimotor Risk Standing Review Panel

NASA Technical Reports Server (NTRS)

Steinberg, Susan

2014-01-01

The Sensorimotor Risk Standing Review Panel (from here on referred to as the SRP) met on December 17 - 18, 2014 in Houston, TX to review the current status of the Risk of Impaired Control of Spacecraft, Associated Systems and Immediate Vehicle Egress due to Vestibular/Sensorimotor Alteration Associated with Space Flight (Sensorimotor Risk) in the Integrated Research Plan (IRP). During the meeting, the SRP received an in-depth briefing of the current status of the Sensorimotor Risk from Dr. Jacob Bloomberg, the Human Research Program (HRP) Sensorimotor Discipline Lead Scientist and Dr. Millard Reschke, the Chief Scientist of the Neuroscience Laboratories at the NASA Johnson Space Center (JSC). The SRP was impressed with the information that Dr. Bloomberg and Dr. Reschke presented and think that the in-person meeting (instead of WebEx/teleconference) allowed for more interactive and thoughtful conversations.

Statistical Determination of the Gating Windows for Respiratory-Gated Radiotherapy Using a Visible Guiding System.

PubMed

Oh, Se An; Yea, Ji Woon; Kim, Sung Kyu

2016-01-01

Respiratory-gated radiation therapy (RGRT) is used to minimize the radiation dose to normal tissue in lung-cancer patients. Although determining the gating window in the respiratory phase of patients is important in RGRT, it is not easy. Our aim was to determine the optimal gating window when using a visible guiding system for RGRT. Between April and October 2014, the breathing signals of 23 lung-cancer patients were recorded with a real-time position management (RPM) respiratory gating system (Varian, USA). We performed statistical analysis with breathing signals to find the optimal gating window for guided breathing in RGRT. When we compared breathing signals before and after the breathing training, 19 of the 23 patients showed statistically significant differences (p < 0.05). The standard deviation of the respiration signals after breathing training was lowest for phases of 30%-70%. The results showed that the optimal gating window in RGRT is 40% (30%-70%) with respect to repeatability for breathing after respiration training with the visible guiding system. RGRT was performed with the RPM system to confirm the usefulness of the visible guiding system. The RPM system and our visible guiding system improve the respiratory regularity, which in turn should improve the accuracy and efficiency of RGRT.

Kinematic markers dissociate error correction from sensorimotor realignment during prism adaptation.

PubMed

O'Shea, Jacinta; Gaveau, Valérie; Kandel, Matthieu; Koga, Kazuo; Susami, Kenji; Prablanc, Claude; Rossetti, Yves

2014-03-01

This study investigated the motor control mechanisms that enable healthy individuals to adapt their pointing movements during prism exposure to a rightward optical shift. In the prism adaptation literature, two processes are typically distinguished. Strategic motor adjustments are thought to drive the pattern of rapid endpoint error correction typically observed during the early stage of prism exposure. This is distinguished from so-called 'true sensorimotor realignment', normally measured with a different pointing task, at the end of prism exposure, which reveals a compensatory leftward 'prism after-effect'. Here, we tested whether each mode of motor compensation - strategic adjustments versus 'true sensorimotor realignment' - could be distinguished, by analyzing patterns of kinematic change during prism exposure. We hypothesized that fast feedforward versus slower feedback error corrective processes would map onto two distinct phases of the reach trajectory. Specifically, we predicted that feedforward adjustments would drive rapid compensation of the initial (acceleration) phase of the reach, resulting in the rapid reduction of endpoint errors typically observed early during prism exposure. By contrast, we expected visual-proprioceptive realignment to unfold more slowly and to reflect feedback influences during the terminal (deceleration) phase of the reach. The results confirmed these hypotheses. Rapid error reduction during the early stage of prism exposure was achieved by trial-by-trial adjustments of the motor plan, which were proportional to the endpoint error feedback from the previous trial. By contrast, compensation of the terminal reach phase unfolded slowly across the duration of prism exposure. Even after 100 trials of pointing through prisms, adaptation was incomplete, with participants continuing to exhibit a small rightward shift in both the reach endpoints and in the terminal phase of reach trajectories. Individual differences in the degree of adaptation of the terminal reach phase predicted the magnitude of prism after-effects. In summary, this study identifies distinct kinematic signatures of fast strategic versus slow sensorimotor realignment processes, which combine to adjust motor performance to compensate for a prismatic shift. © 2013 Elsevier Ltd. All rights reserved.

An error-tuned model for sensorimotor learning

PubMed Central

Sadeghi, Mohsen; Wolpert, Daniel M.

2017-01-01

Current models of sensorimotor control posit that motor commands are generated by combining multiple modules which may consist of internal models, motor primitives or motor synergies. The mechanisms which select modules based on task requirements and modify their output during learning are therefore critical to our understanding of sensorimotor control. Here we develop a novel modular architecture for multi-dimensional tasks in which a set of fixed primitives are each able to compensate for errors in a single direction in the task space. The contribution of the primitives to the motor output is determined by both top-down contextual information and bottom-up error information. We implement this model for a task in which subjects learn to manipulate a dynamic object whose orientation can vary. In the model, visual information regarding the context (the orientation of the object) allows the appropriate primitives to be engaged. This top-down module selection is implemented by a Gaussian function tuned for the visual orientation of the object. Second, each module's contribution adapts across trials in proportion to its ability to decrease the current kinematic error. Specifically, adaptation is implemented by cosine tuning of primitives to the current direction of the error, which we show to be theoretically optimal for reducing error. This error-tuned model makes two novel predictions. First, interference should occur between alternating dynamics only when the kinematic errors associated with each oppose one another. In contrast, dynamics which lead to orthogonal errors should not interfere. Second, kinematic errors alone should be sufficient to engage the appropriate modules, even in the absence of contextual information normally provided by vision. We confirm both these predictions experimentally and show that the model can also account for data from previous experiments. Our results suggest that two interacting processes account for module selection during sensorimotor control and learning. PMID:29253869

Abnormal functional network connectivity among resting-state networks in children with frontal lobe epilepsy.

PubMed

Widjaja, E; Zamyadi, M; Raybaud, C; Snead, O C; Smith, M L

2013-12-01

Epilepsy is considered a disorder of neural networks. The aims of this study were to assess functional connectivity within resting-state networks and functional network connectivity across resting-state networks by use of resting-state fMRI in children with frontal lobe epilepsy and to relate changes in resting-state networks with neuropsychological function. Fifteen patients with frontal lobe epilepsy and normal MR imaging and 14 healthy control subjects were recruited. Spatial independent component analysis was used to identify the resting-state networks, including frontal, attention, default mode network, sensorimotor, visual, and auditory networks. The Z-maps of resting-state networks were compared between patients and control subjects. The relation between abnormal connectivity and neuropsychological function was assessed. Correlations from all pair-wise combinations of independent components were performed for each group and compared between groups. The frontal network was the only network that showed reduced connectivity in patients relative to control subjects. The remaining 5 networks demonstrated both reduced and increased functional connectivity within resting-state networks in patients. There was a weak association between connectivity in frontal network and executive function (P = .029) and a significant association between sensorimotor network and fine motor function (P = .004). Control subjects had 79 pair-wise independent components that showed significant temporal coherence across all resting-state networks except for default mode network-auditory network. Patients had 66 pairs of independent components that showed significant temporal coherence across all resting-state networks. Group comparison showed reduced functional network connectivity between default mode network-attention, frontal-sensorimotor, and frontal-visual networks and increased functional network connectivity between frontal-attention, default mode network-sensorimotor, and frontal-visual networks in patients relative to control subjects. We found abnormal functional connectivity within and across resting-state networks in children with frontal lobe epilepsy. Impairment in functional connectivity was associated with impaired neuropsychological function.

Structured-gate organic field-effect transistors

NASA Astrophysics Data System (ADS)

Aljada, Muhsen; Pandey, Ajay K.; Velusamy, Marappan; Burn, Paul L.; Meredith, Paul; Namdas, Ebinazar B.

2012-06-01

We report the fabrication and electrical characteristics of structured-gate organic field-effect transistors consisting of a gate electrode patterned with three-dimensional pillars. The pillar gate electrode was over-coated with a gate dielectric (SiO2) and solution processed organic semiconductors producing both unipolar p-type and bipolar behaviour. We show that this new structured-gate architecture delivers higher source-drain currents, higher gate capacitance per unit equivalent linear channel area, and enhanced charge injection (electrons and/or holes) versus the conventional planar structure in all modes of operation. For the bipolar field-effect transistor (FET) the maximum source-drain current enhancements in p- and n-channel mode were >600% and 28%, respectively, leading to p and n charge mobilities with the same order of magnitude. Thus, we have demonstrated that it is possible to use the FET architecture to manipulate and match carrier mobilities of material combinations where one charge carrier is normally dominant. Mobility matching is advantageous for creating organic logic circuit elements such as inverters and amplifiers. Hence, the method represents a facile and generic strategy for improving the performance of standard organic semiconductors as well as new materials and blends.

AlGaN/GaN high electron mobility transistors with selective area grown p-GaN gates

NASA Astrophysics Data System (ADS)

Yuliang, Huang; Lian, Zhang; Zhe, Cheng; Yun, Zhang; Yujie, Ai; Yongbing, Zhao; Hongxi, Lu; Junxi, Wang; Jinmin, Li

2016-11-01

We report a selective area growth (SAG) method to define the p-GaN gate of AlGaN/GaN high electron mobility transistors (HEMTs) by metal-organic chemical vapor deposition. Compared with Schottky gate HEMTs, the SAG p-GaN gate HEMTs show more positive threshold voltage (V th) and better gate control ability. The influence of Cp2Mg flux of SAG p-GaN gate on the AlGaN/GaN HEMTs has also been studied. With the increasing Cp2Mg from 0.16 μmol/min to 0.20 μmol/min, the V th raises from -0.67 V to -0.37 V. The maximum transconductance of the SAG HEMT at a drain voltage of 10 V is 113.9 mS/mm while that value of the Schottky HEMT is 51.6 mS/mm. The SAG method paves a promising way for achieving p-GaN gate normally-off AlGaN/GaN HEMTs without dry etching damage. Project supported by the National Natural Sciences Foundation of China (Nos. 61376090, 61306008) and the National High Technology Program of China (No. 2014AA032606).

Gating of human ClC-2 chloride channels and regulation by carboxy-terminal domains

PubMed Central

Garcia-Olivares, Jennie; Alekov, Alexi; Boroumand, Mohammad Reza; Begemann, Birgit; Hidalgo, Patricia; Fahlke, Christoph

2008-01-01

Eukaryotic ClC channels are dimeric proteins with each subunit forming an individual protopore. Single protopores are gated by a fast gate, whereas the slow gate is assumed to control both protopores through a cooperative movement of the two carboxy-terminal domains. We here study the role of the carboxy-terminal domain in modulating fast and slow gating of human ClC-2 channels, a ubiquitously expressed ClC-type chloride channel involved in transepithelial solute transport and in neuronal chloride homeostasis. Partial truncation of the carboxy-terminus abolishes function of ClC-2 by locking the channel in a closed position. However, unlike other isoforms, its complete removal preserves function of ClC-2. ClC-2 channels without the carboxy-terminus exhibit fast and slow gates that activate and deactivate significantly faster than in WT channels. In contrast to the prevalent view, a single carboxy-terminus suffices for normal slow gating, whereas both domains regulate fast gating of individual protopores. Our findings demonstrate that the carboxy-terminus is not strictly required for slow gating and that the cooperative gating resides in other regions of the channel protein. ClC-2 is expressed in neurons and believed to open at negative potentials and increased internal chloride concentrations after intense synaptic activity. We propose that the function of the ClC-2 carboxy-terminus is to slow down the time course of channel activation in order to stabilize neuronal excitability PMID:18801843

Gating of human ClC-2 chloride channels and regulation by carboxy-terminal domains.

PubMed

Garcia-Olivares, Jennie; Alekov, Alexi; Boroumand, Mohammad Reza; Begemann, Birgit; Hidalgo, Patricia; Fahlke, Christoph

2008-11-15

Eukaryotic ClC channels are dimeric proteins with each subunit forming an individual protopore. Single protopores are gated by a fast gate, whereas the slow gate is assumed to control both protopores through a cooperative movement of the two carboxy-terminal domains. We here study the role of the carboxy-terminal domain in modulating fast and slow gating of human ClC-2 channels, a ubiquitously expressed ClC-type chloride channel involved in transepithelial solute transport and in neuronal chloride homeostasis. Partial truncation of the carboxy-terminus abolishes function of ClC-2 by locking the channel in a closed position. However, unlike other isoforms, its complete removal preserves function of ClC-2. ClC-2 channels without the carboxy-terminus exhibit fast and slow gates that activate and deactivate significantly faster than in WT channels. In contrast to the prevalent view, a single carboxy-terminus suffices for normal slow gating, whereas both domains regulate fast gating of individual protopores. Our findings demonstrate that the carboxy-terminus is not strictly required for slow gating and that the cooperative gating resides in other regions of the channel protein. ClC-2 is expressed in neurons and believed to open at negative potentials and increased internal chloride concentrations after intense synaptic activity. We propose that the function of the ClC-2 carboxy-terminus is to slow down the time course of channel activation in order to stabilize neuronal excitability.

Robotic assessment of sensorimotor deficits after traumatic brain injury.

PubMed

Debert, Chantel T; Herter, Troy M; Scott, Stephen H; Dukelow, Sean

2012-06-01

Robotic technology is commonly used to quantify aspects of typical sensorimotor function. We evaluated the feasibility of using robotic technology to assess visuomotor and position sense impairments following traumatic brain injury (TBI). We present results of robotic sensorimotor function testing in 12 subjects with TBI, who had a range of initial severities (9 severe, 2 moderate, 1 mild), and contrast these results with those of clinical tests. We also compared these with robotic test outcomes in persons without disability. For each subject with TBI, a review of the initial injury and neuroradiologic findings was conducted. Following this, each subject completed a number of standardized clinical measures (Fugl-Meyer Assessment, Purdue Peg Board, Montreal Cognitive Assessment, Rancho Los Amigos Scale), followed by two robotic tasks. A visually guided reaching task was performed to assess visuomotor control of the upper limb. An arm position-matching task was used to assess position sense. Robotic task performance in the subjects with TBI was compared with findings in a cohort of 170 person without disabilities. Subjects with TBI demonstrated a broad range of sensory and motor deficits on robotic testing. Notably, several subjects with TBI displayed significant deficits in one or both of the robotic tasks, despite normal scores on traditional clinical motor and cognitive assessment measures. The findings demonstrate the potential of robotic assessments for identifying deficits in visuomotor control and position sense following TBI. Improved identification of neurologic impairments following TBI may ultimately enhance rehabilitation.

Dynamic modulation of corticospinal excitability and short-latency afferent inhibition during onset and maintenance phase of selective finger movement.

PubMed

Cho, Hyun Joo; Panyakaew, Pattamon; Thirugnanasambandam, Nivethida; Wu, Tianxia; Hallett, Mark

2016-06-01

During highly selective finger movement, corticospinal excitability is reduced in surrounding muscles at the onset of movement but this phenomenon has not been demonstrated during maintenance of movement. Sensorimotor integration may play an important role in selective movement. We sought to investigate how corticospinal excitability and short-latency afferent inhibition changes in active and surrounding muscles during onset and maintenance of selective finger movement. Using transcranial magnetic stimulation (TMS) and paired peripheral stimulation, input-output recruitment curve and short-latency afferent inhibition (SAI) were measured in the first dorsal interosseus and abductor digiti minimi muscles during selective index finger flexion. Motor surround inhibition was present only at the onset phase, but not at the maintenance phase of movement. SAI was reduced at onset but not at the maintenance phase of movement in both active and surrounding muscles. Our study showed dynamic changes in corticospinal excitability and sensorimotor modulation for active and surrounding muscles in different movement states. SAI does not appear to contribute to motor surround inhibition at the movement onset phase. Also, there seems to be different inhibitory circuit(s) other than SAI for the movement maintenance phase in order to delineate the motor output selectively when corticospinal excitability is increased in both active and surrounding muscles. This study enhances our knowledge of dynamic changes in corticospinal excitability and sensorimotor interaction in different movement states to understand normal and disordered movements. Published by Elsevier Ireland Ltd.

Two-Photon Excitation STED Microscopy with Time-Gated Detection

PubMed Central

Coto Hernández, Iván; Castello, Marco; Lanzanò, Luca; d’Amora, Marta; Bianchini, Paolo; Diaspro, Alberto; Vicidomini, Giuseppe

2016-01-01

We report on a novel two-photon excitation stimulated emission depletion (2PE-STED) microscope based on time-gated detection. The time-gated detection allows for the effective silencing of the fluorophores using moderate stimulated emission beam intensity. This opens the possibility of implementing an efficient 2PE-STED microscope with a stimulated emission beam running in a continuous-wave. The continuous-wave stimulated emission beam tempers the laser architecture’s complexity and cost, but the time-gated detection degrades the signal-to-noise ratio (SNR) and signal-to-background ratio (SBR) of the image. We recover the SNR and the SBR through a multi-image deconvolution algorithm. Indeed, the algorithm simultaneously reassigns early-photons (normally discarded by the time-gated detection) to their original positions and removes the background induced by the stimulated emission beam. We exemplify the benefits of this implementation by imaging sub-cellular structures. Finally, we discuss of the extension of this algorithm to future all-pulsed 2PE-STED implementationd based on time-gated detection and a nanosecond laser source. PMID:26757892

Structural-metabolic organization of field 4 of the cat brain in normal conditions and after unilateral enucleation of the eye.

PubMed

Zykin, P A

2005-01-01

Comparative data on the structural-metabolic organization of field 4 of the cat brain in normal conditions and after unilateral enucleation of the eye are presented. Cytochrome oxidase was detected histochemically. Data were processed by a computerized method using an original video capture system. Data were obtained demonstrating the uneven distribution of enzyme along sublayer IlIb of field 4 in animals with unilateral enucleation. A hypothesis based on published data is suggested whereby the alternation of high- and low-reactive areas is evidence for the ordering of the retinal representations of the right and left eyes in the sensorimotor cortex.

Inversion channel diamond metal-oxide-semiconductor field-effect transistor with normally off characteristics.

PubMed

Matsumoto, Tsubasa; Kato, Hiromitsu; Oyama, Kazuhiro; Makino, Toshiharu; Ogura, Masahiko; Takeuchi, Daisuke; Inokuma, Takao; Tokuda, Norio; Yamasaki, Satoshi

2016-08-22

We fabricated inversion channel diamond metal-oxide-semiconductor field-effect transistors (MOSFETs) with normally off characteristics. At present, Si MOSFETs and insulated gate bipolar transistors (IGBTs) with inversion channels are widely used because of their high controllability of electric power and high tolerance. Although a diamond semiconductor is considered to be a material with a strong potential for application in next-generation power devices, diamond MOSFETs with an inversion channel have not yet been reported. We precisely controlled the MOS interface for diamond by wet annealing and fabricated p-channel and planar-type MOSFETs with phosphorus-doped n-type body on diamond (111) substrate. The gate oxide of Al2O3 was deposited onto the n-type diamond body by atomic layer deposition at 300 °C. The drain current was controlled by the negative gate voltage, indicating that an inversion channel with a p-type character was formed at a high-quality n-type diamond body/Al2O3 interface. The maximum drain current density and the field-effect mobility of a diamond MOSFET with a gate electrode length of 5 μm were 1.6 mA/mm and 8.0 cm(2)/Vs, respectively, at room temperature.

Sensorimotor abilities predict on-field performance in professional baseball.

PubMed

Burris, Kyle; Vittetoe, Kelly; Ramger, Benjamin; Suresh, Sunith; Tokdar, Surya T; Reiter, Jerome P; Appelbaum, L Gregory

2018-01-08

Baseball players must be able to see and react in an instant, yet it is hotly debated whether superior performance is associated with superior sensorimotor abilities. In this study, we compare sensorimotor abilities, measured through 8 psychomotor tasks comprising the Nike Sensory Station assessment battery, and game statistics in a sample of 252 professional baseball players to evaluate the links between sensorimotor skills and on-field performance. For this purpose, we develop a series of Bayesian hierarchical latent variable models enabling us to compare statistics across professional baseball leagues. Within this framework, we find that sensorimotor abilities are significant predictors of on-base percentage, walk rate and strikeout rate, accounting for age, position, and league. We find no such relationship for either slugging percentage or fielder-independent pitching. The pattern of results suggests performance contributions from both visual-sensory and visual-motor abilities and indicates that sensorimotor screenings may be useful for player scouting.

Sliding-gate valve

DOEpatents

Usnick, George B.; Ward, Gene T.; Blair, Henry O.; Roberts, James W.; Warner, Terry N.

1979-01-01

This invention is a novel valve of the slidable-gate type. The valve is designed especially for long-term use with highly abrasive slurries. The sealing surfaces of the gate are shielded by the valve seats when the valve is fully open or closed, and the gate-to-seat clearance is swept with an inflowing purge gas while the gate is in transit. A preferred form of the valve includes an annular valve body containing an annular seat assembly defining a flow channel. The seat assembly comprises a first seat ring which is slidably and sealably mounted in the body, and a second seat ring which is tightly fitted in the body. These rings cooperatively define an annular gap which, together with passages in the valve body, forms a guideway extending normal to the channel. A plate-type gate is mounted for reciprocation in the guideway between positions where a portion of the plate closes the channel and where a circular aperture in the gate is in register with the channel. The valve casing includes opposed chambers which extend outwardly from the body along the axis of the guideway to accommodate the end portions of the gate. The chambers are sealed from atmosphere; when the gate is in transit, purge gas is admitted to the chambers and flows inwardly through the gate-to-seat-ring, clearance, minimizing buildup of process solids therein. A shaft reciprocated by an external actuator extends into one of the sealed chambers through a shaft seal and is coupled to an end of the gate. Means are provided for adjusting the clearance between the first seat ring and the gate while the valve is in service.

Learning New Sensorimotor Contingencies: Effects of Long-Term Use of Sensory Augmentation on the Brain and Conscious Perception.

PubMed

König, Sabine U; Schumann, Frank; Keyser, Johannes; Goeke, Caspar; Krause, Carina; Wache, Susan; Lytochkin, Aleksey; Ebert, Manuel; Brunsch, Vincent; Wahn, Basil; Kaspar, Kai; Nagel, Saskia K; Meilinger, Tobias; Bülthoff, Heinrich; Wolbers, Thomas; Büchel, Christian; König, Peter

2016-01-01

Theories of embodied cognition propose that perception is shaped by sensory stimuli and by the actions of the organism. Following sensorimotor contingency theory, the mastery of lawful relations between own behavior and resulting changes in sensory signals, called sensorimotor contingencies, is constitutive of conscious perception. Sensorimotor contingency theory predicts that, after training, knowledge relating to new sensorimotor contingencies develops, leading to changes in the activation of sensorimotor systems, and concomitant changes in perception. In the present study, we spell out this hypothesis in detail and investigate whether it is possible to learn new sensorimotor contingencies by sensory augmentation. Specifically, we designed an fMRI compatible sensory augmentation device, the feelSpace belt, which gives orientation information about the direction of magnetic north via vibrotactile stimulation on the waist of participants. In a longitudinal study, participants trained with this belt for seven weeks in natural environment. Our EEG results indicate that training with the belt leads to changes in sleep architecture early in the training phase, compatible with the consolidation of procedural learning as well as increased sensorimotor processing and motor programming. The fMRI results suggest that training entails activity in sensory as well as higher motor centers and brain areas known to be involved in navigation. These neural changes are accompanied with changes in how space and the belt signal are perceived, as well as with increased trust in navigational ability. Thus, our data on physiological processes and subjective experiences are compatible with the hypothesis that new sensorimotor contingencies can be acquired using sensory augmentation.

Learning New Sensorimotor Contingencies: Effects of Long-Term Use of Sensory Augmentation on the Brain and Conscious Perception

PubMed Central

Schumann, Frank; Keyser, Johannes; Goeke, Caspar; Krause, Carina; Wache, Susan; Lytochkin, Aleksey; Ebert, Manuel; Brunsch, Vincent; Wahn, Basil; Kaspar, Kai; Nagel, Saskia K.; Meilinger, Tobias; Bülthoff, Heinrich; Wolbers, Thomas; Büchel, Christian; König, Peter

2016-01-01

Theories of embodied cognition propose that perception is shaped by sensory stimuli and by the actions of the organism. Following sensorimotor contingency theory, the mastery of lawful relations between own behavior and resulting changes in sensory signals, called sensorimotor contingencies, is constitutive of conscious perception. Sensorimotor contingency theory predicts that, after training, knowledge relating to new sensorimotor contingencies develops, leading to changes in the activation of sensorimotor systems, and concomitant changes in perception. In the present study, we spell out this hypothesis in detail and investigate whether it is possible to learn new sensorimotor contingencies by sensory augmentation. Specifically, we designed an fMRI compatible sensory augmentation device, the feelSpace belt, which gives orientation information about the direction of magnetic north via vibrotactile stimulation on the waist of participants. In a longitudinal study, participants trained with this belt for seven weeks in natural environment. Our EEG results indicate that training with the belt leads to changes in sleep architecture early in the training phase, compatible with the consolidation of procedural learning as well as increased sensorimotor processing and motor programming. The fMRI results suggest that training entails activity in sensory as well as higher motor centers and brain areas known to be involved in navigation. These neural changes are accompanied with changes in how space and the belt signal are perceived, as well as with increased trust in navigational ability. Thus, our data on physiological processes and subjective experiences are compatible with the hypothesis that new sensorimotor contingencies can be acquired using sensory augmentation. PMID:27959914

Deep brain stimulation of the inferior colliculus: a possible animal model to study paradoxical kinesia observed in some parkinsonian patients?

PubMed

Melo-Thomas, Liana; Thomas, Uwe

2015-02-15

The inferior colliculus (IC) plays an important role in the normal processing of the acoustic message and is also involved in the filtering of acoustic stimuli of aversive nature. The neural substrate of the IC can also influence haloperidol-induced catalepsy. Considering that (i) paradoxical kinesia, observed in some parkinsonian patients, seems to be dependent of their emotional state and (ii) deep brain stimulation (DBS) represents an alternative therapeutic route for the relief of parkinsonian symptoms, the present study investigated the consequence of DBS at the IC on the catalepsy induced by haloperidol in rats. Additionally, we investigated if DBS of the IC can elicit motor responses in anesthetized rats and whether DBS elicits distinct neural firing patterns of activity at the dorsal cortex (DCIC) or central nucleus (CNIC) of the IC. A significant reduction of the catalepsy response was seen in rats previously given haloperidol and receiving DBS at the IC. In addition, electrical stimulation to the ventral part of the CNIC induced immediate motor responses in anesthetized rats. The neuronal spontaneous activity was higher at the ventral part of the CNIC than the dorsal part. DBS to the ventral part but not to the dorsal part of the CNIC increased the spike rate at neurons a few hundred microns away from the stimulation site. It is possible that the IC plays a role in the sensorimotor gating activated by emotional stimuli, and that DBS at the IC can be a promising new animal model to study paradoxical kinesia in rats. Copyright © 2014 Elsevier B.V. All rights reserved.

Modeling bipolar disorder in mice by increasing acetylcholine or dopamine: Chronic lithium treats most, but not all features

PubMed Central

van Enkhuizen, Jordy; Milienne-Petiot, Morgane; Geyer, Mark A.; Young, Jared W.

2015-01-01

Rationale Bipolar disorder (BD) is a disabling and life-threatening disease characterized by states of depression and mania. New and efficacious treatments have not been forthcoming partly due to a lack of well-validated models representing both facets of BD. Objectives We hypothesized that cholinergic- and dopaminergic-pharmacological manipulations would model depression and mania respectively, each attenuated by lithium treatment. Methods C57BL/6J mice received the acetylcholinesterase inhibitor physostigmine or saline before testing for ‘behavioral despair’ (immobility) in the tail-suspension test (TST) and forced-swim test (FST). Physostigmine effects on exploration and sensorimotor gating were assessed using the cross-species behavioral pattern monitor (BPM) and prepulse inhibition (PPI) paradigms. Other C57BL/6J mice received chronic lithium drinking water (300, 600, or 1200 mg/l) before assessing their effects alone in the BPM or with physostigmine on FST performance. Another group was tested with acute GBR12909 (dopamine transporter inhibitor) and chronic lithium (1000 mg/l) in the BPM. Results Physostigmine (0.03 mg/kg) increased immobility in the TST and FST without affecting activity, exploration, or PPI. Lithium (600 mg/l) resulted in low therapeutic serum concentrations and normalized the physostigmine-increased immobility in the FST. GBR12909 induced mania-like behavior in the BPM of which hyper-exploration was attenuated, though not reversed, after chronic lithium (1000 mg/ml). Conclusions Increased cholinergic levels induced depression-like behavior and hyperdopaminergia induced mania-like behavior in mice, while chronic lithium treated some, but not all, facets of these effects. These data support a cholinergic-monoaminergic mechanism for modeling BD aspects and provide a way to assess novel therapeutics. PMID:26141192

Normal radial migration and lamination are maintained in dyslexia-susceptibility candidate gene homolog Kiaa0319 knockout mice.

PubMed

Martinez-Garay, Isabel; Guidi, Luiz G; Holloway, Zoe G; Bailey, Melissa A G; Lyngholm, Daniel; Schneider, Tomasz; Donnison, Timothy; Butt, Simon J B; Monaco, Anthony P; Molnár, Zoltán; Velayos-Baeza, Antonio

2017-04-01

Developmental dyslexia is a common disorder with a strong genetic component, but the underlying molecular mechanisms are still unknown. Several candidate dyslexia-susceptibility genes, including KIAA0319, DYX1C1, and DCDC2, have been identified in humans. RNA interference experiments targeting these genes in rat embryos have shown impairments in neuronal migration, suggesting that defects in radial cortical migration could be involved in the disease mechanism of dyslexia. Here we present the first characterisation of a Kiaa0319 knockout mouse line. Animals lacking KIAA0319 protein do not show anatomical abnormalities in any of the layered structures of the brain. Neurogenesis and radial migration of cortical projection neurons are not altered, and the intrinsic electrophysiological properties of Kiaa0319-deficient neurons do not differ from those of wild-type neurons. Kiaa0319 overexpression in cortex delays radial migration, but does not affect final neuronal position. However, knockout animals show subtle differences suggesting possible alterations in anxiety-related behaviour and in sensorimotor gating. Our results do not reveal a migration disorder in the mouse model, adding to the body of evidence available for Dcdc2 and Dyx1c1 that, unlike in the rat in utero knockdown models, the dyslexia-susceptibility candidate mouse homolog genes do not play an evident role in neuronal migration. However, KIAA0319 protein expression seems to be restricted to the brain, not only in early developmental stages but also in adult mice, indicative of a role of this protein in brain function. The constitutive and conditional knockout lines reported here will be useful tools for further functional analyses of Kiaa0319.

Atypical antipsychotic clozapine reversed deficit on prepulse inhibition of the acoustic startle reflex produced by microinjection of DOI into the inferior colliculus in rats.

PubMed

de Oliveira, Rodolpho Pereira; Nagaishi, Karen Yuriko; Barbosa Silva, Regina Cláudia

2017-05-15

Dysfunctions of the serotonergic system have been suggested to be important in the neurobiology of schizophrenia. Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of startle. PPI is the normal reduction in the startle response caused by a low intensity non-startling stimulus (prepulse) which is presented shortly before the startle stimulus (pulse). The hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI), a 5-hydroxytryptamine(HT) 2 receptor agonist disrupted PPI in rats. The inferior colliculus (IC) is a critical nucleus of the auditory pathway mediating acoustic PPI. The activation of the IC by the acoustic prepulse reduces startle magnitude. The present study investigated the role of serotonergic transmission in the IC on the expression of acoustic PPI. For that we investigated whether 5-HT2A receptor activation or blockade would affect this response. Unilateral microinjection of DOI (10μg/0.3μl) into the IC disrupted PPI, while microinjection of the 5-HT2A receptor antagonist ritanserin (4μg/0.3μl), into this structure did not alter PPI. We also examined the ability of the atypical antipsychotic clozapine (5.0mg/kg; I.P.) to reverse the disruption of PPI produced by unilateral microinjections of DOI into the IC of rats. Pretreatment with clozapine blocked DOI-induced disruption of PPI. Altogether, these results suggest that serotonin-mediated mechanisms of the IC are involved in the expression of PPI in rodents and that this response is sensitive to atypical antipsychotic clozapine. Copyright © 2017 Elsevier B.V. All rights reserved.

Atypical antipsychotic olanzapine reversed deficit on prepulse inhibition of the acoustic startle reflex produced by microinjection of dizocilpine (MK-801) into the inferior colliculus in rats.

PubMed

Zangrando, Julia; Carvalheira, Renata; Labbate, Giovanna; Medeiros, Priscila; Longo, Beatriz Monteiro; Melo-Thomas, Liana; Silva, Regina Claudia Barbosa

2013-11-15

Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of startle. PPI is the normal reduction in the startle response caused by a low intensity non-startling stimulus (prepulse) which is presented shortly before the startle stimulus (pulse). MK-801 is an NMDA receptor-antagonist known to produce hyperactivity, deficits in prepulse inhibition and social withdrawal, behaviors which correlate well with some of the positive, cognitive and negative symptoms of schizophrenia. The inferior colliculus (IC) is a critical part of the auditory pathway mediating acoustic PPI. The activation of the IC by the acoustic prepulse reduces startle magnitude. Thus, the purpose of the present study was to elucidate the role of glutamatergic transmission in the IC on the expression of acoustic PPI. For that we investigated whether NMDA receptor stimulation or blockade would affect this response. Unilateral microinjections of NMDA (30 nmol/0.5 μL) into the IC did not alter PPI while microinjections of MK-801 (30 nmol/0.5 μL) into this structure disrupted PPI. We also examined the ability of the atypical antipsychotic olanzapine (5.0mg/kg; i.p.) to reverse the disruption of pre-pulse inhibition produced by unilateral microinjections of MK-801 into the IC of rats. Pretreatment with olanzapine blocked MK-801-induced disruption of PPI. Altogether, these results suggest that glutamate-mediated mechanisms of the IC are involved in the expression of PPI in rodents and that this response is sensitive to atypical antipsychotic olanzapine. Copyright © 2013 Elsevier B.V. All rights reserved.

Ion-selective electrolyte-gated field-effect transistors: prerequisites for proper functioning

NASA Astrophysics Data System (ADS)

Kofler, Johannes; Schmoltner, Kerstin; List-Kratochvil, Emil J. W.

2014-10-01

Electrolyte-gated organic field-effect transistors (EGOFETs) used as transducers and amplifiers in potentiometric sensors have recently attracted a significant amount of scientific interest. For that reason, the fundamental prerequisites to achieve a proper potentiometric signal amplification and transduction are examined. First, polarizable as well as non-polarizable semiconductor- and gate-electrolyte- interface combinations are investigated by normal pulse voltammetry. The results of these measurements are correlated with the corresponding transistor characteristics, clarifying the functional principle of EGOFETs and the requirements for high signal amplification. In addition to a good electrical performance, the EGOFET-transducers should also be compatible with the targeted sensing application. Accordingly, the influence of different gate materials and electrolytes on the sensing abilities, are discussed. Even though all physical requirements are met, EGOFETs typically exhibit irreversible degradation, if the gate potential exceeds a certain level. For that reason, EGOFETs have to be operated using a constant source-drain operation mode which is presented by means of an H+ (pH) sensitive ion-sensor.

Characterization of high-dose and high-energy implanted gate and source diode and analysis of lateral spreading of p gate profile in high voltage SiC static induction transistors

NASA Astrophysics Data System (ADS)

Onose, Hidekatsu; Kobayashi, Yutaka; Onuki, Jin

2017-03-01

The effect of the p gate dose on the characteristics of the gate-source diode in SiC static induction transistors (SIT) was investigated. It was found that a dose of 1.5 × 1014 cm-2 yields a pn junction breakdown voltage higher than 60 V and good forward characteristics. A normally on SiC SIT was fabricated and demonstrated. A blocking voltage higher than 2.0 kV at a gate-source voltage of -50 V and on-resistance of 70 mΩ cm2 were obtained. Device simulations were performed to investigate the effect of the lateral spreading. By comparing the measured I-V curves with simulation results, the lateral spreading factor was estimated to be about 0.5. The lateral spreading detrimentally affected the electrical properties of the SIT made using implantations at energies higher than 1 MeV.

AlGaN/GaN-on-Si monolithic power-switching device with integrated gate current booster

NASA Astrophysics Data System (ADS)

Han, Sang-Woo; Jo, Min-Gi; Kim, Hyungtak; Cho, Chun-Hyung; Cha, Ho-Young

2017-08-01

This study investigates the effects of a monolithic gate current booster integrated with an AlGaN/GaN-on-Si power-switching device. The integrated gate current booster was implemented by a single-stage inverter topology consisting of a recessed normally-off AlGaN/GaN MOS-HFET and a mesa resistor. The monolithically integrated gate current booster in a switching FET eliminated the parasitic elements caused by external interconnection and enabled fast switching operation. The gate charging and discharging currents were boosted by the integrated inverter, which significantly reduced both rise and fall times: the rise time was reduced from 626 to 41.26 ns, while the fall time was reduced from 554 to 42.19 ns by the single-stage inverter. When the packaged monolithic power chip was tested under 1 MHz hard-switching operation with VDD = 200 V, the switching loss was found to have been drastically reduced, from 5.27 to 0.55 W.

Feedforward somatosensory inhibition is normal in cervical dystonia.

PubMed

Ferrè, Elisa R; Ganos, Christos; Bhatia, Kailash P; Haggard, Patrick

2015-03-01

Insufficient cortical inhibition is a key pathophysiological finding in dystonia. Subliminal sensory stimuli were reported to transiently inhibit somatosensory processing. Here we investigated whether such subliminal feedforward inhibition is reduced in patients with cervical dystonia. Sixteen cervical dystonia patients and 16 matched healthy controls performed a somatosensory detection task. We measured the drop in sensitivity to detect a threshold-level digital nerve shock when it was preceded by a subliminal conditioning shock, compared to when it was not. Subliminal conditioning shocks reduced sensitivity to threshold stimuli to a similar extent in both patients and controls, suggesting that somatosensory subliminal feedforward inhibition is normal in cervical dystonia. Somatosensory feedforward inhibition was normal in this group of cervical dystonia patients. Our results qualify previous concepts of a general dystonic deficit in sensorimotor inhibitory processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sensorimotor rhythm neurofeedback as adjunct therapy for Parkinson's disease.

PubMed

Philippens, Ingrid H C H M; Wubben, Jacqueline A; Vanwersch, Raymond A P; Estevao, Dave L; Tass, Peter A

2017-08-01

Neurofeedback may enhance compensatory brain mechanisms. EEG-based sensorimotor rhythm neurofeedback training was suggested to be beneficial in Parkinson's disease. In a placebo-controlled study in parkinsonian nonhuman primates we here show that sensorimotor rhythm neurofeedback training reduces MPTP-induced parkinsonian symptoms and both ON and OFF scores during classical L-DOPA treatment. Our findings encourage further development of sensorimotor rhythm neurofeedback training as adjunct therapy for Parkinson's disease which might help reduce L-DOPA-induced side effects.

Beta Peak Frequencies at Rest Correlate with Endogenous GABA+/Cr Concentrations in Sensorimotor Cortex Areas

PubMed Central

Baumgarten, Thomas J.; Oeltzschner, Georg; Hoogenboom, Nienke; Wittsack, Hans-Jörg; Schnitzler, Alfons; Lange, Joachim

2016-01-01

Neuronal oscillatory activity in the beta band (15–30 Hz) is a prominent signal within the human sensorimotor cortex. Computational modeling and pharmacological modulation studies suggest an influence of GABAergic interneurons on the generation of beta band oscillations. Accordingly, studies in humans have demonstrated a correlation between GABA concentrations and power of beta band oscillations. It remains unclear, however, if GABA concentrations also influence beta peak frequencies and whether this influence is present in the sensorimotor cortex at rest and without pharmacological modulation. In the present study, we investigated the relation between endogenous GABA concentration (measured by magnetic resonance spectroscopy) and beta oscillations (measured by magnetoencephalography) at rest in humans. GABA concentrations and beta band oscillations were measured for left and right sensorimotor and occipital cortex areas. A significant positive linear correlation between GABA concentration and beta peak frequency was found for the left sensorimotor cortex, whereas no significant correlations were found for the right sensorimotor and the occipital cortex. The results show a novel connection between endogenous GABA concentration and beta peak frequency at rest. This finding supports previous results that demonstrated a connection between oscillatory beta activity and pharmacologically modulated GABA concentration in the sensorimotor cortex. Furthermore, the results demonstrate that for a predominantly right-handed sample, the correlation between beta band oscillations and endogenous GABA concentrations is evident only in the left sensorimotor cortex. PMID:27258089

Motor Skills Training Improves Sensorimotor Dysfunction and Increases Microtubule-Associated Protein 2 mRNA Expression in Rats with Intracerebral Hemorrhage.

PubMed

Tamakoshi, Keigo; Kawanaka, Kentaro; Onishi, Hideaki; Takamatsu, Yasuyuki; Ishida, Kazuto

2016-08-01

In this study, we examined the effects of motor skills training on the sensorimotor function and the expression of genes associated with synaptic plasticity after intracerebral hemorrhage (ICH) in rats. Male Wistar rats were subjected to ICH or sham operation. ICH was caused by the injection of collagenase into the left striatum. Rats were randomly assigned to no training, acrobatic training, and sham groups. The acrobatic group performed 5 types of acrobatic tasks from 4 to 28 days after surgery. The forelimb sensorimotor function was evaluated over time using forepaw grasping, forelimb placing, and postural instability tests. At 14 and 29 days after the lesion, we analyzed the mRNA expression levels of microtubule-associated protein 2 (MAP2), brain-derived neurotrophic factor, and growth-associated protein 43 in the bilateral sensorimotor cortex (forelimb area) by real-time reverse transcription-polymerase chain reaction. Motor skills training in ICH rats improved the sensorimotor dysfunction significantly from the early phase. The mRNA expression level of MAP2 was upregulated in the ipsilesional sensorimotor cortex by motor skills training at 29 days after the lesion. Our results suggest that sensorimotor functional recovery following motor skills training after ICH is promoted by dendritic growth in the ipsilesional sensorimotor cortex. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Post-Movement Beta Activity in Sensorimotor Cortex Indexes Confidence in the Estimations from Internal Models.

PubMed

Tan, Huiling; Wade, Cian; Brown, Peter

2016-02-03

Beta oscillations are a dominant feature of the sensorimotor system. A transient and prominent increase in beta oscillations is consistently observed across the sensorimotor cortical-basal ganglia network after cessation of voluntary movement: the post-movement beta synchronization (PMBS). Current theories about the function of the PMBS have been focused on either the closure of motor response or the processing of sensory afferance. Computational models of sensorimotor control have emphasized the importance of the integration between feedforward estimation and sensory feedback, and therefore the putative motor and sensory functions of beta oscillations may reciprocally interact with each other and in fact be indissociable. Here we show that the amplitude of sensorimotor PMBS is modulated by the history of visual feedback of task-relevant errors, and negatively correlated with the trial-to-trial exploratory adjustment in a sensorimotor adaptation task in young healthy human subjects. The PMBS also negatively correlated with the uncertainty associated with the feedforward estimation, which was recursively updated in light of new sensory feedback, as identified by a Bayesian learning model. These results reconcile the two opposing motor and sensory views of the function of PMBS, and suggest a unifying theory in which PMBS indexes the confidence in internal feedforward estimation in Bayesian sensorimotor integration. Its amplitude simultaneously reflects cortical sensory processing and signals the need for maintenance or adaptation of the motor output, and if necessary, exploration to identify an altered sensorimotor transformation. For optimal sensorimotor control, sensory feedback and feedforward estimation of a movement's sensory consequences should be weighted by the inverse of their corresponding uncertainties, which require recursive updating in a dynamic environment. We show that post-movement beta activity (13-30 Hz) over sensorimotor cortex in young healthy subjects indexes the evaluation of uncertainty in feedforward estimation. Our work contributes to the understanding of the function of beta oscillations in sensorimotor control, and provides further insight into how aberrant beta activity can contribute to the pathophysiology of movement disorders. Copyright © 2016 Tan et al.

Enzymatic AND logic gates operated under conditions characteristic of biomedical applications.

PubMed

Melnikov, Dmitriy; Strack, Guinevere; Zhou, Jian; Windmiller, Joshua Ray; Halámek, Jan; Bocharova, Vera; Chuang, Min-Chieh; Santhosh, Padmanabhan; Privman, Vladimir; Wang, Joseph; Katz, Evgeny

2010-09-23

Experimental and theoretical analyses of the lactate dehydrogenase and glutathione reductase based enzymatic AND logic gates in which the enzymes and their substrates serve as logic inputs are performed. These two systems are examples of the novel, previously unexplored class of biochemical logic gates that illustrate potential biomedical applications of biochemical logic. They are characterized by input concentrations at logic 0 and 1 states corresponding to normal and pathophysiological conditions. Our analysis shows that the logic gates under investigation have similar noise characteristics. Both significantly amplify random noise present in inputs; however, we establish that for realistic widths of the input noise distributions, it is still possible to differentiate between the logic 0 and 1 states of the output. This indicates that reliable detection of pathophysiological conditions is indeed possible with such enzyme logic systems.

Top-gated field-effect LaAlO{sub 3}/SrTiO{sub 3} devices made by ion-irradiation

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

Hurand, S.; Jouan, A.; Feuillet-Palma, C.

2016-02-01

We present a method to fabricate top-gated field-effect devices in a LaAlO{sub 3}/SrTiO{sub 3} two-dimensional electron gas (2-DEG). Prior to the gate deposition, the realisation of micron size conducting channels in the 2-DEG is achieved by an ion-irradiation with high-energy oxygen ions. After identifying the ion fluence as the key parameter that determines the electrical transport properties of the channels, we demonstrate the field-effect operation. At low temperature, the normal state resistance and the superconducting T{sub c} can be tuned over a wide range by a top-gate voltage without any leakage. A superconductor-to-insulator quantum phase transition is observed for amore » strong depletion of the 2-DEG.« less

Setup of a novel biofeedback prototype for sensorimotor control of the hand and preliminary application in patients with peripheral nerve injuries.

PubMed

Chiu, Haw-Yen; Hsu, Hsiu-Yun; Su, Fong-Chin; Jou, I-Ming; Lin, Cheng-Feng; Kuo, Li-Chieh

2013-02-01

Biofeedback training is widely used for rehabilitative intervention in patients with central or peripheral nervous impairment to train correct movement patterns; however, no biofeedback apparatus is currently available to correct pinch force ratios for patients with sensory deficiencies. A cross-sectional and longitudinal design was used in an observational measurement study for establishing a prototype and to determine the effects of biofeedback intervention, respectively. This study aimed to develop a computerized evaluation and re-education biofeedback (CERB) prototype for application in clinical settings. A CERB prototype was developed integrating pinch apparatus hardware, a biofeedback user-controlled interface, and a data processing/analysis interface to detect momentary pinch performances in 79 people with normal hand sensation. Nine patients with hand sensory impairments were recruited to investigate the effects of training hand function with the CERB prototype. Hand dominance, pinch pattern, and age significantly affected the peak pinch force and force ratio for lifting a 480-g object with a steel surface. In the case of the 79 volunteers with normal hand sensation, hand dominance affected the time lag between peak pinch force and maximum load; however, it was unaffected by pinch pattern or age. Training with the CERB prototype produced significant improvements in force ratio and better performance in the pin insertion subtests, although the results for both 2-point discriminative and Semmes-Weinstein monofilament tests did not change significantly. The intervention findings are preliminary. This study developed a conjunct system suited for evaluating and restoring sensorimotor function for patients with impaired hand sensibility. The results from the participants with normal hand sensation could serve as a reference database for comparison with patients with nerve injuries.

Developmental pattern of diacylglycerol lipase-α (DAGLα) immunoreactivity in brain regions important for song learning and control in the zebra finch (Taeniopygia guttata).

PubMed

Soderstrom, Ken; Wilson, Ashley R

2013-11-01

Zebra finch song is a learned behavior dependent upon successful progress through a sensitive period of late-postnatal development. This learning is associated with maturation of distinct brain nuclei and the fiber tract interconnections between them. We have previously found remarkably distinct and dense CB1 cannabinoid receptor expression within many of these song control brain regions, implying a normal role for endocannabinoid signaling in vocal learning. Activation of CB1 receptors via daily treatments with exogenous agonist during sensorimotor stages of song learning (but not in adulthood) results in persistent alteration of song patterns. Now we are working to understand physiological changes responsible for this cannabinoid-altered vocal learning. We have found that song-altering developmental treatments are associated with changes in expression of endocannabinoid signaling elements, including CB1 receptors and the principal CNS endogenous agonist, 2-AG. Within CNS, 2-AG is produced largely through activity of the α isoform of the enzyme diacylglycerol lipase (DAGLα). To better appreciate the role of 2-AG production in normal vocal development we have determined the spatial distribution of DAGLα expression within zebra finch CNS during vocal development. Early during vocal development at 25 days, DAGLα staining is typically light and of fibroid processes. Staining peaks late in the sensorimotor stage of song learning at 75 days and is characterized by fiber, neuropil and some staining of both small and large cell somata. Results provide insight to the normal role for endocannabinoid signaling in the maturation of brain regions responsible for song learning and vocal-motor output, and suggest mechanisms by which exogenous cannabinoid exposure alters acquisition of this form of vocal communication. Copyright © 2013 Elsevier B.V. All rights reserved.

Sensorimotor coordination and the structure of space.

PubMed

McCollum, Gin

2003-01-01

Embedded in neural and behavioral organization is a structure of sensorimotor space. Both this embedded spatial structure and the structure of physical space inform sensorimotor control. This paper reviews studies in which the gravitational vertical and horizontal are crucial. The mathematical expressions of spatial geometry in these studies indicate methods for investigating sensorimotor control in freefall. In freefall, the spatial structure introduced by gravitation - the distinction between vertical and horizontal - does not exist. However, an astronaut arriving in space carries the physiologically-embedded distinction between horizontal and vertical learned on earth. The physiological organization based on this distinction collapses when the strong otolith activity and other gravitational cues for sensorimotor behavior become unavailable. The mathematical methods in this review are applicable in understanding the changes in physiological organization as an astronaut adapts to sensorimotor control in freefall. Many mathematical languages are available for characterizing the logical structures in physiological organization. Here, group theory is used to characterize basic structure of physical and physiological spaces. Dynamics and topology allow the grouping of trajectory ranges according to the outcomes or attractors. The mathematics of ordered structures express complex orderings, such as in multiphase movements in which different parts of the body are moving in different phase sequences. Conditional dynamics, which combines dynamics with the mathematics of ordered structures, accommodates the parsing of movement sequences into trajectories and transitions. Studies reviewed include those of the sit-to-stand movement and early locomotion, because of the salience of gravitation in those behaviors. Sensorimotor transitions and the conditions leading to them are characterized in conditional dynamic control structures that do not require thinking of an organism as an input-output device. Conditions leading to sensorimotor transitions on earth assume the presence of a gravitational vertical which is lacking in space. Thus, conditions used on earth for sensorimotor transitions may become ambiguous in space. A platform study in which sensorimotor transition conditions are ambiguous and are related to motion sickness is reviewed.

STUDIES IN THE COMMON COLD

PubMed Central

Mills, Katherine C.; Shibley, G. S.; Dochez, A. R.

1928-01-01

1. A study of the Gram-negative, filter-passing, anaerobic organisms, described by Olitsky and Gates, and Gates and McCartney, has been undertaken with a view to determining their general character and their possible rôle in the causation of the common cold. 2. These organisms seem to constitute part of the normal flora of the upper respiratory tract and would seem to bear no etiological relationship to the common cold. PMID:19869406

Clinical Assessment of Tourette Syndrome and Tic Disorders

PubMed Central

Cohen, Stephanie; Leckman, James F.; Bloch, Michael H.

2013-01-01

Tourette Syndrome (TS) is a neuropsychiatric disorder involving multiple motor and phonic tics. Tics, which usually begin between the ages of 6 and 8, are sudden, rapid, stereotyped, and apparently purposeless movements or sounds that involve discrete muscle groups. Individuals with TS experience a variety of different sensory phenomena, including premonitory urges prior to tics and somatic hypersensitivity due to impaired sensorimotor gating. In addition to other conditions, stress, anxiety, fatigue, or other heightened emotional states tend to exacerbate tics, while relaxation, playing sports, and focused concentration on a specific task tend to alleviate tic symptoms. Ninety percent of children with TS also have comorbid conditions, such as Attention deficit hyperactivity disorder (ADHD), Obsessive-compulsive disorder (OCD), or an impulse control disorder. These disorders often cause more problems for the child both at home and at school than tics do alone. Proper diagnosis and treatment of TS involves appropriate evaluation and recognition, not only of tics, but also of these associated conditions. PMID:23206664

Stance-phase force on the opposite limb dictates swing-phase afferent presynaptic inhibition during locomotion

PubMed Central

Hayes, Heather Brant; Chang, Young-Hui

2012-01-01

Presynaptic inhibition is a powerful mechanism for selectively and dynamically gating sensory inputs entering the spinal cord. We investigated how hindlimb mechanics influence presynaptic inhibition during locomotion using pioneering approaches in an in vitro spinal cord–hindlimb preparation. We recorded lumbar dorsal root potentials to measure primary afferent depolarization-mediated presynaptic inhibition and compared their dependence on hindlimb endpoint forces, motor output, and joint kinematics. We found that stance-phase force on the opposite limb, particularly at toe contact, strongly influenced the magnitude and timing of afferent presynaptic inhibition in the swinging limb. Presynaptic inhibition increased in proportion to opposite limb force, as well as locomotor frequency. This form of presynaptic inhibition binds the sensorimotor states of the two limbs, adjusting sensory inflow to the swing limb based on forces generated by the stance limb. Functionally, it may serve to adjust swing-phase sensory transmission based on locomotor task, speed, and step-to-step environmental perturbations. PMID:22442562

Application of Cardiac Gating to Improve the Reproducibility of Intravoxel Incoherent Motion Measurements in the Head and Neck.

PubMed

Kang, Koung Mi; Choi, Seung Hong; Kim, Dong Eun; Yun, Tae Jin; Kim, Ji-Hoon; Sohn, Chul-Ho; Park, Sun-Won

2017-07-10

To prospectively evaluate whether cardiac gating can improve the reproducibility of intravoxel incoherent motion (IVIM) parameters in the head and neck, we performed IVIM diffusion-weighted imaging (DWI) using 4 b values (4b), 4 b values with cardiac gating (4b gating) and 17 b values (17b). We performed IVIM DWI twice per person on nine healthy volunteers using 4b, 4b gating and 17b and five patients with head and neck masses using 4b gating and 17b. The ADC, perfusion fraction (f), diffusion coefficient (D) and perfusion-related diffusion coefficient (D*) were calculated in the brain, masticator muscle, parotid gland, submandibular gland, tonsil and masses. Intraclass coefficient (ICC), Bland-Altman analysis (BAA) and coefficient of variation (CV) were used to assess short-term test-retest reproducibility. Kruskal-Wallis test and Mann-Whitney test were used to investigate whether 4b, 4b gating or 17b had significant influences on the parameters. For normal tissues and masses, ICC was excellent for all maps except the D* map. All parameters showed the lowest CV in the 4b gating. BAA also revealed the narrowest 95% limits of agreement using 4b gating for all parameters. In the subgroup analysis, almost all parameters in brain, muscle, parotid gland and submandibular gland showed the best reproducibility using 4b gating. In the muscle, parotid gland and submandibular gland, the values of ADC, f and D were not significantly different between among the three methods. 4b gating was more reproducible with respect to measurements of IVIM parameters in comparison with 4b or 17b.

Impact of gate engineering in enhancement mode n++GaN/InAlN/AlN/GaN HEMTs

NASA Astrophysics Data System (ADS)

Adak, Sarosij; Swain, Sanjit Kumar; Rahaman, Hafizur; Sarkar, Chandan Kumar

2016-12-01

This paper illustrate the effect of gate material engineering on the performance of enhancement mode n++GaN/InAlN/AlN/GaN high electron mobility transistors (HEMTs). A comparative analysis of key device parameters is discussed for the Triple Material Gate (TMG), Dual Material Gate (DMG) and the Single Material Gate (SMG) structure HEMTs by considering the same device dimensions. The simulation results shows that an significant improvement is noticed in the key analysis parameters such as drain current (Id), transconductance (gm), cut off frequency (fT), RF current gain, maximum cut off frequency (fmax) and RF power gain of the gate material engineered devices with respect to SMG normally off n++GaN/InAlN/AlN/GaN HEMTs. This improvement is due to the existence of the perceivable step in the surface potential along the channel which successfully screens the drain potential variation in the source side of the channel for the gate engineering devices. The analysis suggested that the proposed TMG and DMG engineered structure enhancement mode n++GaN/InAlN/AlN/GaN HEMTs can be considered as a potential device for future high speed, microwave and digital application.

GaN HEMTs with p-GaN gate: field- and time-dependent degradation

NASA Astrophysics Data System (ADS)

Meneghesso, G.; Meneghini, M.; Rossetto, I.; Canato, E.; Bartholomeus, J.; De Santi, C.; Trivellin, N.; Zanoni, E.

2017-02-01

GaN-HEMTs with p-GaN gate have recently demonstrated to be excellent normally-off devices for application in power conversion systems, thanks to the high and robust threshold voltage (VTH>1 V), the high breakdown voltage, and the low dynamic Ron increase. For this reason, studying the stability and reliability of these devices under high stress conditions is of high importance. This paper reports on our most recent results on the field- and time-dependent degradation of GaN-HEMTs with p-GaN gate submitted to stress with positive gate bias. Based on combined step-stress experiments, constant voltage stress and electroluminescence testing we demonstrated that: (i) when submitted to high/positive gate stress, the transistors may show a negative threshold voltage shift, that is ascribed to the injection of holes from the gate metal towards the p-GaN/AlGaN interface; (ii) in a step-stress experiment, the analyzed commercial devices fail at gate voltages higher than 9-10 V, due to the extremely high electric field over the p-GaN/AlGaN stack; (iii) constant voltage stress tests indicate that the failure is also time-dependent and Weibull distributed. The several processes that can explain the time-dependent failure are discussed in the following.

Developing Personalized Sensorimotor Adaptability Countermeasures for Spaceflight

NASA Technical Reports Server (NTRS)

Mulavara, A. P.; Seidler, R. D.; Peters, B.; Cohen, H. S.; Wood, S.; Bloomberg, J. J.

2016-01-01

Astronauts experience sensorimotor disturbances during their initial exposure to microgravity and during the re-adaptation phase following a return to an Earth-gravitational environment. Interestingly, astronauts who return from spaceflight show substantial differences in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which individual astronauts would be affected would improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. In this paper we will be presenting results from our ground-based study that show how behavioral, brain imaging and genomic data may be used to predict individual differences in sensorimotor adaptability to novel sensorimotor environments. This approach will allow us to better design and implement sensorimotor adaptability training countermeasures against decrements in post-mission adaptive capability that are customized for each crewmember's sensory biases, adaptive capacity, brain structure, functional capacities, and genetic predispositions. The ability to customize adaptability training will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes.

Modulation of α power and functional connectivity during facial affect recognition.

PubMed

Popov, Tzvetan; Miller, Gregory A; Rockstroh, Brigitte; Weisz, Nathan

2013-04-03

Research has linked oscillatory activity in the α frequency range, particularly in sensorimotor cortex, to processing of social actions. Results further suggest involvement of sensorimotor α in the processing of facial expressions, including affect. The sensorimotor face area may be critical for perception of emotional face expression, but the role it plays is unclear. The present study sought to clarify how oscillatory brain activity contributes to or reflects processing of facial affect during changes in facial expression. Neuromagnetic oscillatory brain activity was monitored while 30 volunteers viewed videos of human faces that changed their expression from neutral to fearful, neutral, or happy expressions. Induced changes in α power during the different morphs, source analysis, and graph-theoretic metrics served to identify the role of α power modulation and cross-regional coupling by means of phase synchrony during facial affect recognition. Changes from neutral to emotional faces were associated with a 10-15 Hz power increase localized in bilateral sensorimotor areas, together with occipital power decrease, preceding reported emotional expression recognition. Graph-theoretic analysis revealed that, in the course of a trial, the balance between sensorimotor power increase and decrease was associated with decreased and increased transregional connectedness as measured by node degree. Results suggest that modulations in α power facilitate early registration, with sensorimotor cortex including the sensorimotor face area largely functionally decoupled and thereby protected from additional, disruptive input and that subsequent α power decrease together with increased connectedness of sensorimotor areas facilitates successful facial affect recognition.

A normally-off fully AlGaN HEMT with high breakdown voltage and figure of merit for power switch applications

NASA Astrophysics Data System (ADS)

Ebrahimi, Behzad; Asad, Mohsen

2015-07-01

In this paper, we propose a fully AlGaN high electron mobility (HEMT) in which the gate electrode, the barrier and the channel are all AlGaN. The p-type AlGaN gate facilitates the normally-off operation to be compatible with the state-of-the-art power amplifiers. In addition, the AlGaN channel increases the breakdown voltage (VBR) to 598 V due to the higher breakdown field of AlGaN compared to GaN. To assess the efficiency of the proposed structure, its characteristics are compared with the conventional and recently proposed structures. The two-dimensional device simulation results show that the proposed structure has the highest threshold voltage (Vth) and the VBR with the moderately low ON-resistance (RON). These features lead to the highest figure of merit (2.49 × 1012) among the structures which is 83%, 59%, 47% and 49% more than those of the conventional, with a field plate, AlGaN gate and AlGaN channel structures, respectively.

Specific cerebellar activation during Braille reading in blind subjects.

PubMed

Gizewski, Elke R; Timmann, Dagmar; Forsting, Michael

2004-07-01

The traditional view that the cerebellum is involved only in the control of movements has been changed recently. It has been suggested that the human cerebellum is involved in cognition and language. Likewise, besides cortical activity in sensorimotor and visual areas, an increased global activation of the cerebellum has been revealed during Braille reading in blind subjects. Our purpose was to investigate whether there is cerebellar activation during Braille reading by blind subjects other than sensorimotor activation related to finger movements. Early blind and normal sighted subjects were studied with functional magnetic resonance imaging (fMRI) during Braille reading, tactile discrimination of nonsense dots, dots forming symbols, and finger tapping. The experiments were done in block design. Echo planar imaging sequences were carried out on a 1.5-T MR scanner. All blind individuals reading Braille showed robust activation of the posterior and lateral aspects of cerebellar hemispheral lobules Crus I bilaterally but more predominately on the right side. Additionally, activation was present in the medial cerebellum within lobules IV, V, and VIIIA, predominantly on the right. Discriminating nonsense dots did not reveal any activation of Crus I, but did reveal activation within the medial part of lobules IV, V, and VIIIA, predominately on the right. Analysis of sighted subjects during reading of printed text revealed activation of the posterolateral cerebellar hemisphere in Crus I bilaterally, predominantly on the right. Tactile analysis of dots representing symbols revealed an activation in lobules IV and VIII and in right Crus II but not in Crus I. In conclusion, parts of cerebellar activation during Braille reading in blind subjects (i.e., within lobules IV, V, and VIII) overlap with the known hand representation within the cerebellum and are likely related to the sensorimotor part of the task. Cerebellar activation during Braille reading within bilateral Crus I may be due to language processes or inner speech similar to those found during text reading in normal sighted subjects. Object recognition did not account for Crus I activation. Copyright 2004 Wiley-Liss, Inc.

Temporal Dynamics of Sensorimotor Networks in Effort-Based Cost-Benefit Valuation: Early Emergence and Late Net Value Integration.

PubMed

Harris, Alison; Lim, Seung-Lark

2016-07-06

Although physical effort can impose significant costs on decision-making, when and how effort cost information is incorporated into choice remains contested, reflecting a larger debate over the role of sensorimotor networks in specifying behavior. Serial information processing models, in which motor circuits simply implement the output of cognitive systems, hypothesize that effort cost factors into decisions relatively late, via integration with stimulus values into net (combined) value signals in dorsomedial frontal cortex (dmFC). In contrast, ethology-inspired approaches suggest a more active role for the dorsal sensorimotor stream, with effort cost signals emerging rapidly after stimulus onset. Here we investigated the time course of effort cost integration using event-related potentials in hungry human subjects while they made decisions about expending physical effort for appetitive foods. Consistent with the ethological perspective, we found that effort cost was represented from as early as 100-250 ms after stimulus onset, localized to dorsal sensorimotor regions including middle cingulate, somatosensory, and motor/premotor cortices. However, examining the same data time-locked to motor output revealed net value signals combining stimulus value and effort cost approximately -400 ms before response, originating from sensorimotor areas including dmFC, precuneus, and posterior parietal cortex. Granger causal connectivity analysis of the motor effector signal in the time leading to response showed interactions between these sensorimotor regions and ventrolateral prefrontal cortex, a structure associated with adjusting behavior-response mappings. These results suggest that rapid activation of sensorimotor regions interacts with cognitive valuation systems, producing a net value signal reflecting both physical effort and reward contingencies. Although physical effort imposes a cost on choice, when and how effort cost influences neural correlates of decision-making remains contested. This dispute reflects a larger disagreement between cognitive neuroscience and ethology over the role of sensorimotor systems in behavior: are sensorimotor circuits merely implementing the late-stage output of cognitive systems, or engaged rapidly and interactively from early in decision-making? We find that, although early representation of effort cost is associated with sensorimotor regions, these signals are also integrated with cognitive stimulus value representations in the time leading up to motor response. These data suggest that sensorimotor networks interact dynamically with cognitive systems to guide decision-making, providing a first step toward reconciling differing perspectives on sensorimotor roles in valuation and choice. Copyright © 2016 the authors 0270-6474/16/367167-17$15.00/0.

Customizing Countermeasure Prescriptions using Predictive Measures of Sensorimotor Adaptability

NASA Technical Reports Server (NTRS)

Bloomberg, J. J.; Peters, B. T.; Mulavara, A. P.; Miller, C. A.; Batson, C. D.; Wood, S. J.; Guined, J. R.; Cohen, H. S.; Buccello-Stout, R.; DeDios, Y. E.;

Intrinsic brain networks normalize with treatment in pediatric complex regional pain syndrome

PubMed Central

Becerra, Lino; Sava, Simona; Simons, Laura E.; Drosos, Athena M.; Sethna, Navil; Berde, Charles; Lebel, Alyssa A.; Borsook, David

2014-01-01

Pediatric complex regional pain syndrome (P-CRPS) offers a unique model of chronic neuropathic pain as it either resolves spontaneously or through therapeutic interventions in most patients. Here we evaluated brain changes in well-characterized children and adolescents with P-CRPS by measuring resting state networks before and following a brief (median = 3 weeks) but intensive physical and psychological treatment program, and compared them to matched healthy controls. Differences in intrinsic brain networks were observed in P-CRPS compared to controls before treatment (disease state) with the most prominent differences in the fronto-parietal, salience, default mode, central executive, and sensorimotor networks. Following treatment, behavioral measures demonstrated a reduction of symptoms and improvement of physical state (pain levels and motor functioning). Correlation of network connectivities with spontaneous pain measures pre- and post-treatment indicated concomitant reductions in connectivity in salience, central executive, default mode and sensorimotor networks (treatment effects). These results suggest a rapid alteration in global brain networks with treatment and provide a venue to assess brain changes in CRPS pre- and post-treatment, and to evaluate therapeutic effects. PMID:25379449

Music Making as a Tool for Promoting Brain Plasticity across the Life Span

PubMed Central

Wan, Catherine Y.; Schlaug, Gottfried

2010-01-01

Playing a musical instrument is an intense, multisensory, and motor experience that usually commences at an early age and requires the acquisition and maintenance of a range of skills over the course of a musician's lifetime. Thus, musicians offer an excellent human model for studying the brain effects of acquiring specialized sensorimotor skills. For example, musicians learn and repeatedly practice the association of motor actions with specific sound and visual patterns (musical notation) while receiving continuous multisensory feedback. This association learning can strengthen connections between auditory and motor regions (e.g., arcuate fasciculus) while activating multimodal integration regions (e.g., around the intraparietal sulcus). We argue that training of this neural network may produce cross-modal effects on other behavioral or cognitive operations that draw on this network. Plasticity in this network may explain some of the sensorimotor and cognitive enhancements that have been associated with music training. These enhancements suggest the potential for music making as an interactive treatment or intervention for neurological and developmental disorders, as well as those associated with normal aging. PMID:20889966

Music making as a tool for promoting brain plasticity across the life span.

PubMed

Wan, Catherine Y; Schlaug, Gottfried

2010-10-01

Playing a musical instrument is an intense, multisensory, and motor experience that usually commences at an early age and requires the acquisition and maintenance of a range of skills over the course of a musician's lifetime. Thus, musicians offer an excellent human model for studying the brain effects of acquiring specialized sensorimotor skills. For example, musicians learn and repeatedly practice the association of motor actions with specific sound and visual patterns (musical notation) while receiving continuous multisensory feedback. This association learning can strengthen connections between auditory and motor regions (e.g., arcuate fasciculus) while activating multimodal integration regions (e.g., around the intraparietal sulcus). We argue that training of this neural network may produce cross-modal effects on other behavioral or cognitive operations that draw on this network. Plasticity in this network may explain some of the sensorimotor and cognitive enhancements that have been associated with music training. These enhancements suggest the potential for music making as an interactive treatment or intervention for neurological and developmental disorders, as well as those associated with normal aging.

Decoding Intention at Sensorimotor Timescales

PubMed Central

Salvaris, Mathew; Haggard, Patrick

2014-01-01

The ability to decode an individual's intentions in real time has long been a ‘holy grail’ of research on human volition. For example, a reliable method could be used to improve scientific study of voluntary action by allowing external probe stimuli to be delivered at different moments during development of intention and action. Several Brain Computer Interface applications have used motor imagery of repetitive actions to achieve this goal. These systems are relatively successful, but only if the intention is sustained over a period of several seconds; much longer than the timescales identified in psychophysiological studies for normal preparation for voluntary action. We have used a combination of sensorimotor rhythms and motor imagery training to decode intentions in a single-trial cued-response paradigm similar to those used in human and non-human primate motor control research. Decoding accuracy of over 0.83 was achieved with twelve participants. With this approach, we could decode intentions to move the left or right hand at sub-second timescales, both for instructed choices instructed by an external stimulus and for free choices generated intentionally by the participant. The implications for volition are considered. PMID:24523855

Normal-inverse bimodule operation Hadamard transform ion mobility spectrometry.

PubMed

Hong, Yan; Huang, Chaoqun; Liu, Sheng; Xia, Lei; Shen, Chengyin; Chu, Yannan

2018-10-31

In order to suppress or eliminate the spurious peaks and improve signal-to-noise ratio (SNR) of Hadamard transform ion mobility spectrometry (HT-IMS), a normal-inverse bimodule operation Hadamard transform - ion mobility spectrometry (NIBOHT-IMS) technique was developed. In this novel technique, a normal and inverse pseudo random binary sequence (PRBS) was produced in sequential order by an ion gate controller and utilized to control the ion gate of IMS, and then the normal HT-IMS mobility spectrum and the inverse HT-IMS mobility spectrum were obtained. A NIBOHT-IMS mobility spectrum was gained by subtracting the inverse HT-IMS mobility spectrum from normal HT-IMS mobility spectrum. Experimental results demonstrate that the NIBOHT-IMS technique can significantly suppress or eliminate the spurious peaks, and enhance the SNR by measuring the reactant ions. Furthermore, the gas CHCl 3 and CH 2 Br 2 were measured for evaluating the capability of detecting real sample. The results show that the NIBOHT-IMS technique is able to eliminate the spurious peaks and improve the SNR notably not only for the detection of larger ion signals but also for the detection of small ion signals. Copyright © 2018 Elsevier B.V. All rights reserved.

A qualitative electron microscopic study of the corticopontine projections after neonatal cerebellar hemispherectomy.

PubMed

Leong, S K

1980-08-04

The present study shows that 3--5 days following lesions of the dentate and interposed nuclei in normal adult rats degenerating axons and axon terminals can be detected in the contralateral pontine gray. The degenerating axon terminals form Gray's type I axo-dendritic contacts with fine and intermediate dendrites measuring between 0.8--2.4 microns. The present study also investigates, by electron microscopy, the synaptic rearrangement of the sensorimotor corticopontine projections following neonatal left cerebellar hemispherectomy. Following neonatal left cerebellar hemispherectomy, the right sensorimotor and adjacent cortex (SMC) presents a very dense ipsilateral and a modest amount of contralateral corticopontine projections in contrast with a predominantly ipsilateral corticopontine projection seen in the normal adult rat. As with the ipsilateral corticopontine projection seen in the normal adult animal, the bilateral corticopontine projections seen in the experimental animals form contacts with dendrites suggestive of Gray's type I synapses. While the corticopontine projections in normal control animals form synapses with fine dendrites measuring 0.2--1.2 micron the corticopontine projections in the experimental animals form synaptic relations with fine dendrites and with intermediate dendrites measuring 0.2--2.4 microns. As the normal cerebellopontine fibers from the dentate and interposed nuclei also form axo-dendritic synapses on fine and intermediate dendrites and the contracts formed are also of Gray's type I synapses, it is possible that some of the newly formed corticopontine fibers in the experimental animals might have replaced the cerebellopontine fibers synapsing on intermediate dendrites. Synaptic rearrangement appears to take place as suggested by the presence of synaptic complexes in which one axon terminal contacts two or more dendrites or two or more axon terminals contact one dendrite. Such complexes are frequently seen to undergo degeneration following the right SMC lesion in the experimental animals. Other complex synaptic structures are also present in both the right and left pontine gray in the experimental animals. They are not seen to undergo degeneration following the right SMC lesions. Occasional features of neuronal reaction could still be seen in both sides of the pontine gray for as long as 3--6 months after the neonatal cerebellar lesions.

The Behavioral Pediatrics Feeding Assessment Scale is a reliable and valid tool for Greek children.

PubMed

Sdravou, Katerina S L T; Evangeliou, Athanasios; Tentzidou, Kyriaki; Sotiriadou, Fotini; Stasinou, Eleanna; Fotoulaki, Maria

2018-05-11

Development of normal feeding is a highly complex sensorimotor process that depends upon the integration of neurological maturation, internal motivation and experiential learning (1-3). Disruption of the child's feeding process can lead to feeding problems during infancy and early childhood. One of the most widely used and validated scales for measuring whether a child's feeding problem has clinical significance is the Behavioral Pediatric Feeding Assessment Scale (BPFAS) (4). The objective of this study was to translate the BPFAS into Greek and culturally adapt the scale to evaluate the psychometric properties among the Greek parents of normally developing children. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Enhanced detection threshold for in vivo cortical stimulation produced by Hebbian conditioning

NASA Astrophysics Data System (ADS)

Rebesco, James M.; Miller, Lee E.

2011-02-01

Normal brain function requires constant adaptation, as an organism learns to associate important sensory stimuli with the appropriate motor actions. Neurological disorders may disrupt these learned associations and require the nervous system to reorganize itself. As a consequence, neural plasticity is a crucial component of normal brain function and a critical mechanism for recovery from injury. Associative, or Hebbian, pairing of pre- and post-synaptic activity has been shown to alter stimulus-evoked responses in vivo; however, to date, such protocols have not been shown to affect the animal's subsequent behavior. We paired stimulus trains separated by a brief time delay to two electrodes in rat sensorimotor cortex, which changed the statistical pattern of spikes during subsequent behavior. These changes were consistent with strengthened functional connections from the leading electrode to the lagging electrode. We then trained rats to respond to a microstimulation cue, and repeated the paradigm using the cue electrode as the leading electrode. This pairing lowered the rat's ICMS-detection threshold, with the same dependence on intra-electrode time lag that we found for the functional connectivity changes. The timecourse of the behavioral effects was very similar to that of the connectivity changes. We propose that the behavioral changes were a consequence of strengthened functional connections from the cue electrode to other regions of sensorimotor cortex. Such paradigms might be used to augment recovery from a stroke, or to promote adaptation in a bidirectional brain-machine interface.

Circuit mechanisms of sensorimotor learning

PubMed Central

Makino, Hiroshi; Hwang, Eun Jung; Hedrick, Nathan G.; Komiyama, Takaki

2016-01-01

SUMMARY The relationship between the brain and the environment is flexible, forming the foundation for our ability to learn. Here we review the current state of our understanding of the modifications in the sensorimotor pathway related to sensorimotor learning. We divide the process in three hierarchical levels with distinct goals: 1) sensory perceptual learning, 2) sensorimotor associative learning, and 3) motor skill learning. Perceptual learning optimizes the representations of important sensory stimuli. Associative learning and the initial phase of motor skill learning are ensured by feedback-based mechanisms that permit trial-and-error learning. The later phase of motor skill learning may primarily involve feedback-independent mechanisms operating under the classic Hebbian rule. With these changes under distinct constraints and mechanisms, sensorimotor learning establishes dedicated circuitry for the reproduction of stereotyped neural activity patterns and behavior. PMID:27883902

Disentangling multimodal processes in social categorization.

PubMed

Slepian, Michael L

2015-03-01

The current work examines the role of sensorimotor processes (manipulating whether visual exposure to hard and soft stimuli encourage sensorimotor simulation) and metaphor processes (assessing whether participants have understanding of a pertinent metaphor: "hard" Republicans and "soft" Democrats) in social categorization. Using new methodology to disassociate these multimodal processes (i.e., semantic, metaphoric, and sensorimotoric), the current work demonstrates that both sensorimotor and metaphor processes, combined, are needed to find an effect upon conceptual processing, providing evidence in support of the combined importance of these two theorized components. When participants comprehended the metaphor of hard Republicans and soft Democrats, and when encouraged to simulate sensorimotor experiences of hard and soft stimuli, those stimuli influenced categorization of faces as Republican and Democrat. Copyright © 2014 Elsevier B.V. All rights reserved.

Type-2 diabetes mellitus reduces cortical thickness and decreases oxidative metabolism in sensorimotor regions after stroke.

PubMed

Ferris, Jennifer K; Peters, Sue; Brown, Katlyn E; Tourigny, Katherine; Boyd, Lara A

2018-05-01

Individuals with type-2 diabetes mellitus experience poor motor outcomes after ischemic stroke. Recent research suggests that type-2 diabetes adversely impacts neuronal integrity and function, yet little work has considered how these neuronal changes affect sensorimotor outcomes after stroke. Here, we considered how type-2 diabetes impacted the structural and metabolic function of the sensorimotor cortex after stroke using volumetric magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We hypothesized that the combination of chronic stroke and type-2 diabetes would negatively impact the integrity of sensorimotor cortex as compared to individuals with chronic stroke alone. Compared to stroke alone, individuals with stroke and diabetes had lower cortical thickness bilaterally in the primary somatosensory cortex, and primary and secondary motor cortices. Individuals with stroke and diabetes also showed reduced creatine levels bilaterally in the sensorimotor cortex. Contralesional primary and secondary motor cortex thicknesses were negatively related to sensorimotor outcomes in the paretic upper-limb in the stroke and diabetes group such that those with thinner primary and secondary motor cortices had better motor function. These data suggest that type-2 diabetes alters cerebral energy metabolism, and is associated with thinning of sensorimotor cortex after stroke. These factors may influence motor outcomes after stroke.

Persistent neurochemical and behavioral abnormalities in adulthood despite early iron supplementation for perinatal iron deficiency anemia in rats⋆

PubMed Central

Felt, Barbara T.; Beard, John L.; Schallert, Timothy; Shao, Jie; Aldridge, J. Wayne; Connor, James R.; Georgieff, Michael K.; Lozoff, Betsy

2006-01-01

Background Iron deficiency anemia (IDA) has been associated with altered cognitive, motor, and social-emotional outcomes in human infants. We recently reported that rats with chronic perinatal IDA, had altered regional brain iron, monoamines, and sensorimotor skill emergence during early development. Objective To examine the long-term consequences of chronic perinatal IDA on behavior, brain iron and monoamine systems after dietary iron treatment in rats. Methods Sixty dams were randomly assigned to iron-sufficient (CN) or low-iron (EID) diets during gestation and lactation. Thereafter, all offspring were fed the iron-sufficient diet, assessed for hematology and behavior after weaning and into adulthood and for brain measures as adults (regional brain iron, monoamines, dopamine and serotonin transporters, and dopamine receptor). Behavioral assessments included sensorimotor function, general activity, response to novelty, spatial alternation, and spatial water maze performance. Results Hematology and growth were similar for EID and CN rats by postnatal day 35. In adulthood, EID thalamic iron content was lower. Monoamines, dopamine transporter, and dopamine receptor concentrations did not differ from CN. EID serotonin transporter concentration was reduced in striatum and related regions. EID rats had persisting sensorimotor deficits (delayed vibrissae-evoked forelimb placing, longer sticker removal time, and more imperfect grooming chains), were more hesitant in novel settings, and had poorer spatial water maze performance than CN. General activity and spatial alternation were similar for EID and CN. Conclusion Rats that had chronic perinatal IDA showed behavioral impairments that suggest persistent striatal dopamine and hippocampal dysfunction despite normalization of hematology, growth and most brain measures. PMID:16713640

Neurological and robot-controlled induction of an apparition.

PubMed

Blanke, Olaf; Pozeg, Polona; Hara, Masayuki; Heydrich, Lukas; Serino, Andrea; Yamamoto, Akio; Higuchi, Toshiro; Salomon, Roy; Seeck, Margitta; Landis, Theodor; Arzy, Shahar; Herbelin, Bruno; Bleuler, Hannes; Rognini, Giulio

2014-11-17

Tales of ghosts, wraiths, and other apparitions have been reported in virtually all cultures. The strange sensation that somebody is nearby when no one is actually present and cannot be seen (feeling of a presence, FoP) is a fascinating feat of the human mind, and this apparition is often covered in the literature of divinity, occultism, and fiction. Although it is described by neurological and psychiatric patients and healthy individuals in different situations, it is not yet understood how the phenomenon is triggered by the brain. Here, we performed lesion analysis in neurological FoP patients, supported by an analysis of associated neurological deficits. Our data show that the FoP is an illusory own-body perception with well-defined characteristics that is associated with sensorimotor loss and caused by lesions in three distinct brain regions: temporoparietal, insular, and especially frontoparietal cortex. Based on these data and recent experimental advances of multisensory own-body illusions, we designed a master-slave robotic system that generated specific sensorimotor conflicts and enabled us to induce the FoP and related illusory own-body perceptions experimentally in normal participants. These data show that the illusion of feeling another person nearby is caused by misperceiving the source and identity of sensorimotor (tactile, proprioceptive, and motor) signals of one's own body. Our findings reveal the neural mechanisms of the FoP, highlight the subtle balance of brain mechanisms that generate the experience of "self" and "other," and advance the understanding of the brain mechanisms responsible for hallucinations in schizophrenia. Copyright © 2014 Elsevier Ltd. All rights reserved.

Determination of prospective displacement-based gate threshold for respiratory-gated radiation delivery from retrospective phase-based gate threshold selected at 4D CT simulation

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

Vedam, S.; Archambault, L.; Starkschall, G.

2007-11-15

Four-dimensional (4D) computed tomography (CT) imaging has found increasing importance in the localization of tumor and surrounding normal structures throughout the respiratory cycle. Based on such tumor motion information, it is possible to identify the appropriate phase interval for respiratory gated treatment planning and delivery. Such a gating phase interval is determined retrospectively based on tumor motion from internal tumor displacement. However, respiratory-gated treatment is delivered prospectively based on motion determined predominantly from an external monitor. Therefore, the simulation gate threshold determined from the retrospective phase interval selected for gating at 4D CT simulation may not correspond to the deliverymore » gate threshold that is determined from the prospective external monitor displacement at treatment delivery. The purpose of the present work is to establish a relationship between the thresholds for respiratory gating determined at CT simulation and treatment delivery, respectively. One hundred fifty external respiratory motion traces, from 90 patients, with and without audio-visual biofeedback, are analyzed. Two respiratory phase intervals, 40%-60% and 30%-70%, are chosen for respiratory gating from the 4D CT-derived tumor motion trajectory. From residual tumor displacements within each such gating phase interval, a simulation gate threshold is defined based on (a) the average and (b) the maximum respiratory displacement within the phase interval. The duty cycle for prospective gated delivery is estimated from the proportion of external monitor displacement data points within both the selected phase interval and the simulation gate threshold. The delivery gate threshold is then determined iteratively to match the above determined duty cycle. The magnitude of the difference between such gate thresholds determined at simulation and treatment delivery is quantified in each case. Phantom motion tests yielded coincidence of simulation and delivery gate thresholds to within 0.3%. For patient data analysis, differences between simulation and delivery gate thresholds are reported as a fraction of the total respiratory motion range. For the smaller phase interval, the differences between simulation and delivery gate thresholds are 8{+-}11% and 14{+-}21% with and without audio-visual biofeedback, respectively, when the simulation gate threshold is determined based on the mean respiratory displacement within the 40%-60% gating phase interval. For the longer phase interval, corresponding differences are 4{+-}7% and 8{+-}15% with and without audio-visual biofeedback, respectively. Alternatively, when the simulation gate threshold is determined based on the maximum average respiratory displacement within the gating phase interval, greater differences between simulation and delivery gate thresholds are observed. A relationship between retrospective simulation gate threshold and prospective delivery gate threshold for respiratory gating is established and validated for regular and nonregular respiratory motion. Using this relationship, the delivery gate threshold can be reliably estimated at the time of 4D CT simulation, thereby improving the accuracy and efficiency of respiratory-gated radiation delivery.« less

Determination of prospective displacement-based gate threshold for respiratory-gated radiation delivery from retrospective phase-based gate threshold selected at 4D CT simulation.

PubMed

Vedam, S; Archambault, L; Starkschall, G; Mohan, R; Beddar, S

2007-11-01

Four-dimensional (4D) computed tomography (CT) imaging has found increasing importance in the localization of tumor and surrounding normal structures throughout the respiratory cycle. Based on such tumor motion information, it is possible to identify the appropriate phase interval for respiratory gated treatment planning and delivery. Such a gating phase interval is determined retrospectively based on tumor motion from internal tumor displacement. However, respiratory-gated treatment is delivered prospectively based on motion determined predominantly from an external monitor. Therefore, the simulation gate threshold determined from the retrospective phase interval selected for gating at 4D CT simulation may not correspond to the delivery gate threshold that is determined from the prospective external monitor displacement at treatment delivery. The purpose of the present work is to establish a relationship between the thresholds for respiratory gating determined at CT simulation and treatment delivery, respectively. One hundred fifty external respiratory motion traces, from 90 patients, with and without audio-visual biofeedback, are analyzed. Two respiratory phase intervals, 40%-60% and 30%-70%, are chosen for respiratory gating from the 4D CT-derived tumor motion trajectory. From residual tumor displacements within each such gating phase interval, a simulation gate threshold is defined based on (a) the average and (b) the maximum respiratory displacement within the phase interval. The duty cycle for prospective gated delivery is estimated from the proportion of external monitor displacement data points within both the selected phase interval and the simulation gate threshold. The delivery gate threshold is then determined iteratively to match the above determined duty cycle. The magnitude of the difference between such gate thresholds determined at simulation and treatment delivery is quantified in each case. Phantom motion tests yielded coincidence of simulation and delivery gate thresholds to within 0.3%. For patient data analysis, differences between simulation and delivery gate thresholds are reported as a fraction of the total respiratory motion range. For the smaller phase interval, the differences between simulation and delivery gate thresholds are 8 +/- 11% and 14 +/- 21% with and without audio-visual biofeedback, respectively, when the simulation gate threshold is determined based on the mean respiratory displacement within the 40%-60% gating phase interval. For the longer phase interval, corresponding differences are 4 +/- 7% and 8 +/- 15% with and without audiovisual biofeedback, respectively. Alternatively, when the simulation gate threshold is determined based on the maximum average respiratory displacement within the gating phase interval, greater differences between simulation and delivery gate thresholds are observed. A relationship between retrospective simulation gate threshold and prospective delivery gate threshold for respiratory gating is established and validated for regular and nonregular respiratory motion. Using this relationship, the delivery gate threshold can be reliably estimated at the time of 4D CT simulation, thereby improving the accuracy and efficiency of respiratory-gated radiation delivery.

Cardiac-gated parametric images from 82 Rb PET from dynamic frames and direct 4D reconstruction.

PubMed

Germino, Mary; Carson, Richard E

2018-02-01

Cardiac perfusion PET data can be reconstructed as a dynamic sequence and kinetic modeling performed to quantify myocardial blood flow, or reconstructed as static gated images to quantify function. Parametric images from dynamic PET are conventionally not gated, to allow use of all events with lower noise. An alternative method for dynamic PET is to incorporate the kinetic model into the reconstruction algorithm itself, bypassing the generation of a time series of emission images and directly producing parametric images. So-called "direct reconstruction" can produce parametric images with lower noise than the conventional method because the noise distribution is more easily modeled in projection space than in image space. In this work, we develop direct reconstruction of cardiac-gated parametric images for 82 Rb PET with an extension of the Parametric Motion compensation OSEM List mode Algorithm for Resolution-recovery reconstruction for the one tissue model (PMOLAR-1T). PMOLAR-1T was extended to accommodate model terms to account for spillover from the left and right ventricles into the myocardium. The algorithm was evaluated on a 4D simulated 82 Rb dataset, including a perfusion defect, as well as a human 82 Rb list mode acquisition. The simulated list mode was subsampled into replicates, each with counts comparable to one gate of a gated acquisition. Parametric images were produced by the indirect (separate reconstructions and modeling) and direct methods for each of eight low-count and eight normal-count replicates of the simulated data, and each of eight cardiac gates for the human data. For the direct method, two initialization schemes were tested: uniform initialization, and initialization with the filtered iteration 1 result of the indirect method. For the human dataset, event-by-event respiratory motion compensation was included. The indirect and direct methods were compared for the simulated dataset in terms of bias and coefficient of variation as a function of iteration. Convergence of direct reconstruction was slow with uniform initialization; lower bias was achieved in fewer iterations by initializing with the filtered indirect iteration 1 images. For most parameters and regions evaluated, the direct method achieved the same or lower absolute bias at matched iteration as the indirect method, with 23%-65% lower noise. Additionally, the direct method gave better contrast between the perfusion defect and surrounding normal tissue than the indirect method. Gated parametric images from the human dataset had comparable relative performance of indirect and direct, in terms of mean parameter values per iteration. Changes in myocardial wall thickness and blood pool size across gates were readily visible in the gated parametric images, with higher contrast between myocardium and left ventricle blood pool in parametric images than gated SUV images. Direct reconstruction can produce parametric images with less noise than the indirect method, opening the potential utility of gated parametric imaging for perfusion PET. © 2017 American Association of Physicists in Medicine.

Intramuscular Neurotrophin-3 normalizes low threshold spinal reflexes, reduces spasms and improves mobility after bilateral corticospinal tract injury in rats.

PubMed

Kathe, Claudia; Hutson, Thomas Haynes; McMahon, Stephen Brendan; Moon, Lawrence David Falcon

2016-10-19

Brain and spinal injury reduce mobility and often impair sensorimotor processing in the spinal cord leading to spasticity. Here, we establish that complete transection of corticospinal pathways in the pyramids impairs locomotion and leads to increased spasms and excessive mono- and polysynaptic low threshold spinal reflexes in rats. Treatment of affected forelimb muscles with an adeno-associated viral vector (AAV) encoding human Neurotrophin-3 at a clinically-feasible time-point after injury reduced spasticity. Neurotrophin-3 normalized the short latency Hoffmann reflex to a treated hand muscle as well as low threshold polysynaptic spinal reflexes involving afferents from other treated muscles. Neurotrophin-3 also enhanced locomotor recovery. Furthermore, the balance of inhibitory and excitatory boutons in the spinal cord and the level of an ion co-transporter in motor neuron membranes required for normal reflexes were normalized. Our findings pave the way for Neurotrophin-3 as a therapy that treats the underlying causes of spasticity and not only its symptoms.

Separate Gating Mechanisms Mediate the Regulation of K2P Potassium Channel TASK-2 by Intra- and Extracellular pH*

PubMed Central

Niemeyer, María Isabel; Cid, L. Pablo; Peña-Münzenmayer, Gaspar; Sepúlveda, Francisco V.

2010-01-01

TASK-2 (KCNK5 or K2P5.1) is a background K+ channel that is opened by extracellular alkalinization and plays a role in renal bicarbonate reabsorption and central chemoreception. Here, we demonstrate that in addition to its regulation by extracellular protons (pHo) TASK-2 is gated open by intracellular alkalinization. The following pieces of evidence suggest that the gating process controlled by intracellular pH (pHi) is independent from that under the command of pHo. It was not possible to overcome closure by extracellular acidification by means of intracellular alkalinization. The mutant TASK-2-R224A that lacks sensitivity to pHo had normal pHi-dependent gating. Increasing extracellular K+ concentration acid shifts pHo activity curve of TASK-2 yet did not affect pHi gating of TASK-2. pHo modulation of TASK-2 is voltage-dependent, whereas pHi gating was not altered by membrane potential. These results suggest that pHo, which controls a selectivity filter external gate, and pHi act at different gating processes to open and close TASK-2 channels. We speculate that pHi regulates an inner gate. We demonstrate that neutralization of a lysine residue (Lys245) located at the C-terminal end of transmembrane domain 4 by mutation to alanine abolishes gating by pHi. We postulate that this lysine acts as an intracellular pH sensor as its mutation to histidine acid-shifts the pHi-dependence curve of TASK-2 as expected from its lower pKa. We conclude that intracellular pH, together with pHo, is a critical determinant of TASK-2 activity and therefore of its physiological function. PMID:20351106

A one-dimensional diffusion analogy model for estimation of tide heights in selected tidal marshes in Connecticut

USGS Publications Warehouse

Bjerklie, David M.; O’Brien, Kevin; Rozsa, Ron

2013-01-01

A one-dimensional diffusion analogy model for estimating tide heights in coastal marshes was developed and calibrated by using data from previous tidal-marsh studies. The method is simpler to use than other one- and two-dimensional hydrodynamic models because it does not require marsh depth and tidal prism information; however, the one-dimensional diffusion analogy model cannot be used to estimate tide heights, flow velocities, and tide arrival times for tide conditions other than the highest tide for which it is calibrated. Limited validation of the method indicates that it has an accuracy within 0.3 feet. The method can be applied with limited calibration information that is based entirely on remote sensing or geographic information system data layers. The method can be used to estimate high-tide heights in tidal wetlands drained by tide gates where tide levels cannot be observed directly by opening the gates without risk of flooding properties and structures. A geographic information system application of the method is demonstrated for Sybil Creek marsh in Branford, Connecticut. The tidal flux into this marsh is controlled by two tide gates that prevent full tidal inundation of the marsh. The method application shows reasonable tide heights for the gates-closed condition (the normal condition) and the one-gate-open condition on the basis of comparison with observed heights. The condition with all tide gates open (two gates) was simulated with the model; results indicate where several structures would be flooded if the gates were removed as part of restoration efforts or if the tide gates were to fail.

Addressing Anger Using Sensorimotor Psychotherapy and Cognitive Behaviour Therapy

ERIC Educational Resources Information Center

Flynn, Sarah M.

2010-01-01

A young woman initiated counselling services at a community agency to address her explosive anger that was a remnant of childhood physical and emotional abuse. Sensorimotor psychotherapy was used to help this client learn how to monitor and regulate her sensorimotor processes. In conjunction with this approach, Cognitive behavioural therapy was…

Toward a self-organizing pre-symbolic neural model representing sensorimotor primitives.

PubMed

Zhong, Junpei; Cangelosi, Angelo; Wermter, Stefan

2014-01-01

The acquisition of symbolic and linguistic representations of sensorimotor behavior is a cognitive process performed by an agent when it is executing and/or observing own and others' actions. According to Piaget's theory of cognitive development, these representations develop during the sensorimotor stage and the pre-operational stage. We propose a model that relates the conceptualization of the higher-level information from visual stimuli to the development of ventral/dorsal visual streams. This model employs neural network architecture incorporating a predictive sensory module based on an RNNPB (Recurrent Neural Network with Parametric Biases) and a horizontal product model. We exemplify this model through a robot passively observing an object to learn its features and movements. During the learning process of observing sensorimotor primitives, i.e., observing a set of trajectories of arm movements and its oriented object features, the pre-symbolic representation is self-organized in the parametric units. These representational units act as bifurcation parameters, guiding the robot to recognize and predict various learned sensorimotor primitives. The pre-symbolic representation also accounts for the learning of sensorimotor primitives in a latent learning context.

Toward a self-organizing pre-symbolic neural model representing sensorimotor primitives

PubMed Central

Zhong, Junpei; Cangelosi, Angelo; Wermter, Stefan

2014-01-01

The acquisition of symbolic and linguistic representations of sensorimotor behavior is a cognitive process performed by an agent when it is executing and/or observing own and others' actions. According to Piaget's theory of cognitive development, these representations develop during the sensorimotor stage and the pre-operational stage. We propose a model that relates the conceptualization of the higher-level information from visual stimuli to the development of ventral/dorsal visual streams. This model employs neural network architecture incorporating a predictive sensory module based on an RNNPB (Recurrent Neural Network with Parametric Biases) and a horizontal product model. We exemplify this model through a robot passively observing an object to learn its features and movements. During the learning process of observing sensorimotor primitives, i.e., observing a set of trajectories of arm movements and its oriented object features, the pre-symbolic representation is self-organized in the parametric units. These representational units act as bifurcation parameters, guiding the robot to recognize and predict various learned sensorimotor primitives. The pre-symbolic representation also accounts for the learning of sensorimotor primitives in a latent learning context. PMID:24550798

Understanding the mechanisms of cognitive impairments in developmental coordination disorder.

PubMed

Deng, Shining; Li, Wei-Guang; Ding, Jing; Wu, Jinlin; Zhang, Yuanyuan; Li, Fei; Shen, Xiaoming

2014-01-01

Developmental coordination disorder (DCD), a neurodevelopmental disability in which a child's motor coordination difficulties significantly interfere with activities of daily life or academic achievement, together with additional symptoms of diseases with childhood sensorimotor impairments, increases the risk of many cognitive problems. This exhibits the dynamic interplay between sensorimotor and cognition systems. However, the brain structures and pathways involved have remained unknown over the past decades. Here, we review developments in recent years that elucidate the neural mechanisms involved in the sensorimotor-cognitive difficulties. First, we briefly address the clinical and epidemiological discoveries in DCD as well as its comorbidities. Subsequently, we group the growing evidence including our findings that support the notion that sensorimotor manipulation indeed affects the cognition development at systematic, circuitry, cellular, and molecular levels. This corresponds to changes in diverse brain regions, synaptic plasticity, and neurotransmitter and receptor activity during development under these effects. Finally, we address the treatment potentials of task-oriented sensorimotor enhancement, as a new therapeutic strategy for cognitive rehabilitation, based on our current understanding of the neurobiology of cognitive-sensorimotor interaction.

The linguistic context effects on the processing of body-object interaction words: An ERP study on second language learners.

PubMed

Xue, Jin; Marmolejo-Ramos, Fernando; Pei, Xuna

2015-07-10

Embodied theories of cognition argue that the processing of both concrete and abstract concepts requires the activation of sensorimotor systems. The present study examined the time course for embedding a sensorimotor context in order to elicit sensitivity to the sensorimotor consequences of understanding body-object interaction (BOI) words. In the study, Event-Related Potentials (ERPs) were recorded while subjects performed a sentence acceptability task. Target BOI words were preceded by rich or poor sensorimotor sentential contexts. The behavioural results replicated previous findings in that high BOI words received a response faster than low BOI words. In addition to this, however, there was a context effect in the sensorimotor region as well as a BOI effect in the parietal region (involved in object representation). The results indicate that the sentential sensorimotor context contributes to the subsequent BOI processing and that action-and perception-related language leads to the activation of the same brain areas, which is consistent with the embodiment theory. Copyright © 2015 Elsevier B.V. All rights reserved.

Using virtual reality to augment perception, enhance sensorimotor adaptation, and change our minds.

PubMed

Wright, W Geoffrey

2014-01-01

Technological advances that involve human sensorimotor processes can have both intended and unintended effects on the central nervous system (CNS). This mini review focuses on the use of virtual environments (VE) to augment brain functions by enhancing perception, eliciting automatic motor behavior, and inducing sensorimotor adaptation. VE technology is becoming increasingly prevalent in medical rehabilitation, training simulators, gaming, and entertainment. Although these VE applications have often been shown to optimize outcomes, whether it be to speed recovery, reduce training time, or enhance immersion and enjoyment, there are inherent drawbacks to environments that can potentially change sensorimotor calibration. Across numerous VE studies over the years, we have investigated the effects of combining visual and physical motion on perception, motor control, and adaptation. Recent results from our research involving exposure to dynamic passive motion within a visually-depicted VE reveal that short-term exposure to augmented sensorimotor discordance can result in systematic aftereffects that last beyond the exposure period. Whether these adaptations are advantageous or not, remains to be seen. Benefits as well as risks of using VE-driven sensorimotor stimulation to enhance brain processes will be discussed.

Sensorimotor System Measurement Techniques

PubMed Central

Riemann, Bryan L.; Myers, Joseph B.; Lephart, Scott M.

2002-01-01

Objective: To provide an overview of currently available sensorimotor assessment techniques. Data Sources: We drew information from an extensive review of the scientific literature conducted in the areas of proprioception, neuromuscular control, and motor control measurement. Literature searches were conducted using MEDLINE for the years 1965 to 1999 with the key words proprioception, somatosensory evoked potentials, nerve conduction testing, electromyography, muscle dynamometry, isometric, isokinetic, kinetic, kinematic, posture, equilibrium, balance, stiffness, neuromuscular, sensorimotor, and measurement. Additional sources were collected using the reference lists of identified articles. Data Synthesis: Sensorimotor measurement techniques are discussed with reference to the underlying physiologic mechanisms, influential factors and locations of the variable within the system, clinical research questions, limitations of the measurement technique, and directions for future research. Conclusions/Recommendations: The complex interactions and relationships among the individual components of the sensorimotor system make measuring and analyzing specific characteristics and functions difficult. Additionally, the specific assessment techniques used to measure a variable can influence attained results. Optimizing the application of sensorimotor research to clinical settings can, therefore, be best accomplished through the use of common nomenclature to describe underlying physiologic mechanisms and specific measurement techniques. PMID:16558672

A novel nanoscaled Schottky barrier based transmission gate and its digital circuit applications

NASA Astrophysics Data System (ADS)

Kumar, Sunil; Loan, Sajad A.; Alamoud, Abdulrahman M.

2017-04-01

In this work we propose and simulate a compact nanoscaled transmission gate (TG) employing a single Schottky barrier based transistor in the transmission path and a single transistor based Sajad-Sunil-Schottky (SSS) device as an inverter. Therefore, just two transistors are employed to realize a complete transmission gate which normally consumes four transistors in the conventional technology. The transistors used to realize the transmission path and the SSS inverter in the proposed TG are the double gate Schottky barrier devices, employing stacks of two metal silicides, platinum silicide (PtSi) and erbium silicide (ErSi). It has been observed that the realization of the TG gate by the proposed technology has resulted into a compact structure, with reduced component count, junctions, interconnections and regions in comparison to the conventional technology. The further focus of this work is on the application part of the proposed technology. So for the first time, the proposed technology has been used to realize various combinational circuits, like a two input AND gate, a 2:1 multiplexer and a two input XOR circuits. It has been observed that the transistor count has got reduced by half in a TG, two input AND gate, 2:1 multiplexer and in a two input XOR gate. Therefore, a significant reduction in transistor count and area requirement can be achieved by using the proposed technology. The proposed technology can be also used to perform the compact realization of other combinational and sequential circuitry in future.

Anomalous single-electron transfer in common-gate quadruple-dot single-electron devices with asymmetric junction capacitances

NASA Astrophysics Data System (ADS)

Imai, Shigeru; Ito, Masato

2018-06-01

In this paper, anomalous single-electron transfer in common-gate quadruple-dot turnstile devices with asymmetric junction capacitances is revealed. That is, the islands have the same total number of excess electrons at high and low gate voltages of the swing that transfers a single electron. In another situation, two electrons enter the islands from the source and two electrons leave the islands for the source and drain during a gate voltage swing cycle. First, stability diagrams of the turnstile devices are presented. Then, sequences of single-electron tunneling events by gate voltage swings are investigated, which demonstrate the above-mentioned anomalous single-electron transfer between the source and the drain. The anomalous single-electron transfer can be understood by regarding the four islands as “three virtual islands and a virtual source or drain electrode of a virtual triple-dot device”. The anomalous behaviors of the four islands are explained by the normal behavior of the virtual islands transferring a single electron and the behavior of the virtual electrode.

Pinch-off mechanism in double-lateral-gate junctionless transistors fabricated by scanning probe microscope based lithography

PubMed Central

Dehzangi, Arash; Abedini, Alam; Abdullah, Ahmad Makarimi; Saion, Elias; Hutagalung, Sabar D; Hamidon, Mohd N; Hassan, Jumiah

2012-01-01

Summary A double-lateral-gate p-type junctionless transistor is fabricated on a low-doped (1015) silicon-on-insulator wafer by a lithography technique based on scanning probe microscopy and two steps of wet chemical etching. The experimental transfer characteristics are obtained and compared with the numerical characteristics of the device. The simulation results are used to investigate the pinch-off mechanism, from the flat band to the off state. The study is based on the variation of the carrier density and the electric-field components. The device is a pinch-off transistor, which is normally in the on state and is driven into the off state by the application of a positive gate voltage. We demonstrate that the depletion starts from the bottom corner of the channel facing the gates and expands toward the center and top of the channel. Redistribution of the carriers due to the electric field emanating from the gates creates an electric field perpendicular to the current, toward the bottom of the channel, which provides the electrostatic squeezing of the current. PMID:23365794

Distribution and function of voltage-gated sodium channels in the nervous system.

PubMed

Wang, Jun; Ou, Shao-Wu; Wang, Yun-Jie

2017-11-02

Voltage-gated sodium channels (VGSCs) are the basic ion channels for neuronal excitability, which are crucial for the resting potential and the generation and propagation of action potentials in neurons. To date, at least nine distinct sodium channel isoforms have been detected in the nervous system. Recent studies have identified that voltage-gated sodium channels not only play an essential role in the normal electrophysiological activities of neurons but also have a close relationship with neurological diseases. In this study, the latest research findings regarding the structure, type, distribution, and function of VGSCs in the nervous system and their relationship to neurological diseases, such as epilepsy, neuropathic pain, brain tumors, neural trauma, and multiple sclerosis, are reviewed in detail.

The effects of gated speech on the fluency of speakers who stutter

PubMed Central

Howell, Peter

2007-01-01

It is known that the speech of people who stutter improves when the speaker’s own vocalization is changed while the participant is speaking. One explanation of these effects is the disruptive rhythm hypothesis (DRH). DRH maintains that the manipulated sound only needs to disturb timing to affect speech control. The experiment investigated whether speech that was gated on and off (interrupted) affected the speech control of speakers who stutter. Eight children who stutter read a passage when they heard their voice normally and when the speech was gated. Fluency was enhanced (fewer errors were made and time to read a set passage was reduced) when speech was interrupted in this way. The results support the DRH. PMID:17726328

The effects of gated speech on the fluency of speakers who stutter.

PubMed

Howell, Peter

2007-01-01

It is known that the speech of people who stutter improves when the speaker's own vocalization is changed while the participant is speaking. One explanation of these effects is the disruptive rhythm hypothesis (DRH). The DRH maintains that the manipulated sound only needs to disturb timing to affect speech control. The experiment investigated whether speech that was gated on and off (interrupted) affected the speech control of speakers who stutter. Eight children who stutter read a passage when they heard their voice normally and when the speech was gated. Fluency was enhanced (fewer errors were made and time to read a set passage was reduced) when speech was interrupted in this way. The results support the DRH. Copyright 2007 S. Karger AG, Basel.

Transport Signatures of Quasiparticle Poisoning in a Majorana Island.

PubMed

Albrecht, S M; Hansen, E B; Higginbotham, A P; Kuemmeth, F; Jespersen, T S; Nygård, J; Krogstrup, P; Danon, J; Flensberg, K; Marcus, C M

2017-03-31

We investigate effects of quasiparticle poisoning in a Majorana island with strong tunnel coupling to normal-metal leads. In addition to the main Coulomb blockade diamonds, "shadow" diamonds appear, shifted by 1e in gate voltage, consistent with transport through an excited (poisoned) state of the island. Comparison to a simple model yields an estimate of parity lifetime for the strongly coupled island (∼1  μs) and sets a bound for a weakly coupled island (>10  μs). Fluctuations in the gate-voltage spacing of Coulomb peaks at high field, reflecting Majorana hybridization, are enhanced by the reduced lever arm at strong coupling. When converted from gate voltage to energy units, fluctuations are consistent with previous measurements.

Sensorimotor control and neuromuscular activity of the shoulder in adolescent competitive swimmers with generalized joint hypermobility.

PubMed

Frydendal, Thomas; Eshøj, Henrik; Liaghat, Behnam; Edouard, Pascal; Søgaard, Karen; Juul-Kristensen, Birgit

2018-05-05

Shoulder pain is highly prevalent in competitive swimmers, and generalized joint hypermobility (GJH) is considered a risk factor. Sensorimotor control deficiencies and altered neuromuscular activation of the shoulder may represent underlying factors. To investigate whether competitive swimmers with GJH including shoulder hypermobility (GJHS) differ in shoulder sensorimotor control and muscle activity from those without GJH and no shoulder hypermobility (NGJH). Competitive swimmers (aged 13-17) were recruited. GJHS or NGJH status was determined using the Beighton score (0-9) and Rotès-Quérol test (positive/negative). Inclusion criteria for GJHS were a Beighton score ≥5 and minimum one hypermobile shoulder, while NGJH was defined as a Beighton score ≤3 and no shoulder hypermobility. Three prone lying, upper-extremity weight-bearing shoulder stabilometric tests were performed on a force platform: Bilateral upper-extremity support eyes open (BL-EO) and eyes closed (BL-EC) and unilateral upper-extremity support eyes open (UL-EO). Surface electromyography (SEMG) was measured from the upper trapezius, lower trapezius, serratus anterior, infraspinatus and pectoralis major muscles. SEMG was normalized using maximal voluntary isometric contractions and presented relative to maximal voluntary SEMG (%MVE). Co-contraction index (CCI) was calculated for the following muscle pairs: upper trapezius-lower trapezius, upper trapezius-serratus anterior, and infraspinatus-pectoralis major. Between-group differences in stabilometric parameters, %MVE, and CCI were analyzed with a mixed effects model. Thirty-eight swimmers were enrolled as GJHS (n = 19) or NGJH (n = 19). There were no group differences in stabilometric parameters or CCI. GJHS displayed significantly decreased (29%) pectoralis major activity during BL-EO compared to NGJH (5.35 ± 1.77%MVE vs. 7.51 ± 1.96%MVE; p = 0.043). Adolescent competitive swimmers with GJHS displayed no shoulder sensorimotor control deficiencies and no generally altered shoulder muscle activity pattern, except for decreased pectoralis major activity in BL-EO. Longitudinal studies are needed to investigate whether decreased pectoralis major activation contributes to the development of shoulder pain in swimmers with GJHS. Copyright © 2018 Elsevier B.V. All rights reserved.

Exhibition of Stochastic Resonance in Vestibular Perception

NASA Technical Reports Server (NTRS)

Galvan-Garza, R. C.; Clark, T. K.; Merfeld, D. M.; Bloomberg, J. J.; Oman, C. M.; Mulavara, A. P.

2016-01-01

Astronauts experience sensorimotor changes during spaceflight, particularly during G-transitions. Post flight sensorimotor changes include spatial disorientation, along with postural and gait instability that may degrade operational capabilities of the astronauts and endanger the crew. A sensorimotor countermeasure that mitigates these effects would improve crewmember safety and decrease risk. The goal of this research is to investigate the potential use of stochastic vestibular stimulation (SVS) as a technology to improve sensorimotor function. We hypothesize that low levels of SVS will improve sensorimotor perception through the phenomenon of stochastic resonance (SR), when the response of a nonlinear system to a weak input signal is enhanced by the application of a particular nonzero level of noise. This study aims to advance the development of SVS as a potential countermeasure by 1) demonstrating the exhibition of stochastic resonance in vestibular perception, a vital component of sensorimotor function, 2) investigating the repeatability of SR exhibition, and 3) determining the relative contribution of the semicircular canals (SCC) and otolith (OTO) organs to vestibular perceptual SR. A constant current stimulator was used to deliver bilateral bipolar SVS via electrodes placed on each of the mastoid processes, as previously done. Vestibular perceptual motion recognition thresholds were measured using a 6-degree of freedom MOOG platform and a 150 trial 3-down/1-up staircase procedure. In the first test session, we measured vestibular perceptual thresholds in upright roll-tilt at 0.2 Hz (SCC+OTO) with SVS ranging from 0-700 µA. In a second test session a week later, we re-measured roll-tilt thresholds with 0, optimal (from test session 1), and 1500 µA SVS levels. A subset of these subjects, plus naive subjects, participated in two additional test sessions in which we measured thresholds in supine roll-rotation at 0.2 Hz (SCC) and upright y-translation at 1 Hz (OTO) with SVS up to 700 µA. A sinusoidal galvanic vestibular stimulation (GVS) perceptual threshold was also measured on each test day and used to normalize the SVS levels across subjects. In roll-tilt thresholds with SVS, the characteristic SR curve was qualitatively exhibited in 10 of 12 subjects, and the improvement in motion threshold was significant in 6 subjects, indicating that optimal SVS improved passive body motion perception in a way that is consistent with classical SR theory. A probabilistic comparison to numeric simulations further validated these experimental results. On the second test session, 4 out of the 10 SR exhibitors showed repeated improvement with SVS compared to the no SVS condition. Data collection is ongoing for the last two test sessions in which SCC and OTO only perceptual motion recognition thresholds are being measured with SVS. The final results of these test sessions will give insight into whether vestibular perceptual SR can occur when only one type of vestibular sensor is sensing motion or if it is more evident when sensory integration between the SCC and OTO is occurring during the motion. The overall purpose of this research is to further quantify the effects of SVS on various sensorimotor tasks and to gain a more fundamental understanding of how SVS causes SR in the vestibular system. In the context of human space flight, results from this research will help in understanding how SVS may be practically implemented in the future as a component of a comprehensive countermeasure plan for G-transition adaptation.

Acute quadriplegia caused by necrotizing myopathy in a renal transplant recipient with severe pneumonia: acute onset and complete recovery.

PubMed

Tu, Guo-Wei; Song, Jie-Qiong; Ting, Simon Kang Seng; Ju, Min-Jie; He, Hong-Yu; Dong, Ji-Hong; Luo, Zhe

2015-02-03

Critical illness polyneuropathy and myopathy are multifaceted complications that follow severe illnesses involving the sensorimotor axons and proximal skeletal muscles. These syndromes have rarely been reported among renal transplant recipients. In this paper, we report a case of acute quadriplegia caused by necrotizing myopathy in a renal transplant recipient with severe pneumonia. The muscle strength in the patient's extremities improved gradually after four weeks of comprehensive treatment, and his daily life activities were normal a year after being discharged.

SU-E-J-169: The Dosimetric and Temporal Effects of Respiratory-Gated Radiation Therapy in Lung Cancer Patients

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

Rouabhi, O; Gross, B; Xia, J

2015-06-15

Purpose: To evaluate the dosimetric and temporal effects of high dose rate treatment mode for respiratory-gated radiation therapy in lung cancer patients. Methods: Treatment plans from five lung cancer patients (3 nongated (Group 1), 2 gated at 80EX-80IN (Group 2)) were retrospectively evaluated. The maximum tumor motions range from 6–12 mm. Using the same planning criteria, four new treatment plans, corresponding to four gating windows (20EX–20IN, 40EX–40IN, 60EX–60IN, and 80EX–80IN), were generated for each patient. Mean tumor dose (MTD), mean lung dose (MLD), and lung V20 were used to assess the dosimetric effects. A MATLAB algorithm was developed to computemore » treatment time by considering gantry rotation time, time to position collimator leaves, dose delivery time (scaled relative to the gating window), and communication overhead. Treatment delivery time for each plan was estimated using a 500 MU/min dose rate for the original plans and a 1500 MU/min dose rate for the gated plans. Results: Differences in MTD were less than 1Gy across plans for all five patients. MLD and lung V20 were on average reduced between −16.1% to −6.0% and −20.0% to −7.2%, respectively for non-gated plans when compared with the corresponding gated plans, and between − 5.8% to −4.2% and −7.0% to −5.4%, respectively for plans originally gated at 80EX–80IN when compared with the corresponding 20EX-20IN to 60EX– 60IN gated plans. Treatment delivery times of gated plans using high dose rate were reduced on average between −19.7% (−1.9min) to −27.2% (−2.7min) for originally non-gated plans and −15.6% (−0.9min) to −20.3% (−1.2min) for originally 80EX-80IN gated plans. Conclusion: Respiratory-gated radiation therapy in lung cancer patients can reduce lung toxicity, while maintaining tumor dose. Using a gated high-dose-rate treatment, delivery time comparable to non-gated normal-dose-rate treatment can be achieved. This research is supported by Siemens Medical Solutions USA, Inc.« less

Sensorimotor Learning Biases Choice Behavior: A Learning Neural Field Model for Decision Making

PubMed Central

Schöner, Gregor; Gail, Alexander

2012-01-01

According to a prominent view of sensorimotor processing in primates, selection and specification of possible actions are not sequential operations. Rather, a decision for an action emerges from competition between different movement plans, which are specified and selected in parallel. For action choices which are based on ambiguous sensory input, the frontoparietal sensorimotor areas are considered part of the common underlying neural substrate for selection and specification of action. These areas have been shown capable of encoding alternative spatial motor goals in parallel during movement planning, and show signatures of competitive value-based selection among these goals. Since the same network is also involved in learning sensorimotor associations, competitive action selection (decision making) should not only be driven by the sensory evidence and expected reward in favor of either action, but also by the subject's learning history of different sensorimotor associations. Previous computational models of competitive neural decision making used predefined associations between sensory input and corresponding motor output. Such hard-wiring does not allow modeling of how decisions are influenced by sensorimotor learning or by changing reward contingencies. We present a dynamic neural field model which learns arbitrary sensorimotor associations with a reward-driven Hebbian learning algorithm. We show that the model accurately simulates the dynamics of action selection with different reward contingencies, as observed in monkey cortical recordings, and that it correctly predicted the pattern of choice errors in a control experiment. With our adaptive model we demonstrate how network plasticity, which is required for association learning and adaptation to new reward contingencies, can influence choice behavior. The field model provides an integrated and dynamic account for the operations of sensorimotor integration, working memory and action selection required for decision making in ambiguous choice situations. PMID:23166483

The possibility of left dominant activation of the sensorimotor cortex during lip protrusion in men.

PubMed

Fukunaga, Atsushi; Ohira, Takayuki; Kamba, Masayuki; Ogawa, Seiji; Akiyama, Takenori; Kawase, Takeshi

2009-09-01

Lip protrusion requires bilateral symmetrical movements of the facial muscles, but the laterality of the activated sensorimotor cortex corresponding to the area of the face activated during lip protrusion remains under discussion. In this study, blood-oxygenation-level-dependent (BOLD) responses in the sensorimotor cortex during non-verbal lip protrusion were evaluated in a 3T magnetic field in twenty healthy right-handed subjects. The results showed that the activated sensorimotor area on the left side was larger than that on the right side, and there was a statistically significant difference in the number of activated voxels between the left and right sensorimotor cortex in an individual study of the male group, although approximately symmetrical motor action potentials of facial muscles were recorded during lip protrusion. There was a statistically significant difference in interaction between the hemisphere (right and left) and sex (men and women) and multiple comparison test showed statistical significant differences between "men and right" and "men and left", and between "men and left" and "women and left". The peak value of the percent changes in BOLD signal responses on the left side was approximately twice as high as that on the right side in the males of the group, though the bilateral sensorimotor cortex was almost equally activated in the females in the group. In addition, the left primary sensory area related to the face area was significantly activated as a region where Male was more active than Female in a general linear model (multi-study, multisubject) analysis. This study revealed the possibility that the left sensorimotor cortex was more closely involved in non-verbal mouth movement in men, suggesting sex-related differences in sensorimotor cortex activation.

Effects of Increasing Neuromuscular Electrical Stimulation Current Intensity on Cortical Sensorimotor Network Activation: A Time Domain fNIRS Study

PubMed Central

Zucchelli, Lucia; Perrey, Stephane; Contini, Davide; Caffini, Matteo; Spinelli, Lorenzo; Kerr, Graham; Quaresima, Valentina; Ferrari, Marco; Torricelli, Alessandro

2015-01-01

Neuroimaging studies have shown neuromuscular electrical stimulation (NMES)-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O2Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O2Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions. PMID:26158464

Effects of Increasing Neuromuscular Electrical Stimulation Current Intensity on Cortical Sensorimotor Network Activation: A Time Domain fNIRS Study.

PubMed

Muthalib, Makii; Re, Rebecca; Zucchelli, Lucia; Perrey, Stephane; Contini, Davide; Caffini, Matteo; Spinelli, Lorenzo; Kerr, Graham; Quaresima, Valentina; Ferrari, Marco; Torricelli, Alessandro

2015-01-01

Neuroimaging studies have shown neuromuscular electrical stimulation (NMES)-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O2Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O2Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions.

Neurodegeneration and Sensorimotor Deficits in the Mouse Model of Traumatic Brain Injury

PubMed Central

Bhowmick, Saurav; D‘Mello, Veera; Ponery, Nizmi; Abdul-Muneer, P. M.

2018-01-01

Traumatic brain injury (TBI) can result in persistent sensorimotor and cognitive deficits, which occur through a cascade of deleterious pathophysiological events over time. In this study, we investigated the hypothesis that neurodegeneration caused by TBI leads to impairments in sensorimotor function. TBI induces the activation of the caspase-3 enzyme, which triggers cell apoptosis in an in vivo model of fluid percussion injury (FPI). We analyzed caspase-3 mediated apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and poly (ADP-ribose) polymerase (PARP) and annexin V western blotting. We correlated the neurodegeneration with sensorimotor deficits by conducting the animal behavioral tests including grid walk, balance beam, the inverted screen test, and the climb test. Our study demonstrated that the excess cell death or neurodegeneration correlated with the neuronal dysfunction and sensorimotor impairments associated with TBI. PMID:29316623

Effects of bilateral and unilateral locus coeruleus lesions on beam-walking recovery after subsequent unilateral sensorimotor cortex suction-ablation in the rat.

PubMed

Goldstein, L B

1997-01-01

The recovery of beam-walking ability following a unilateral sensorimotor cortex lesion in the rat is hypothesized to be noradrenergically-mediated. We carried out two experiments to further test this hypothesis. In the first experiment, bilateral 6-hydroxydopamine locus coeruleus (LC) lesions or sham LC lesions were made 2 weeks prior to a right sensorimotor cortex suction-ablation lesion or sham cortex lesion. In the second experiment, unilateral left or right LC lesions or sham LC lesions were made 2 weeks prior to a right sensorimotor cortex lesion or sham cortex lesion. Beam-walking recovery was measured over the 12 days following cortex lesioning in each experiment. Bilateral, unilateral left, and unilateral right LC lesions resulted in impaired recovery. These data provide additional support for the hypothesis that beam-walking recovery after sensorimotor cortex injury is, at least in part, noradrenergically mediated.

Oxidative Modulation of Voltage-Gated Potassium Channels

PubMed Central

Sahoo, Nirakar; Hoshi, Toshinori

2014-01-01

Abstract Significance: Voltage-gated K+ channels are a large family of K+-selective ion channel protein complexes that open on membrane depolarization. These K+ channels are expressed in diverse tissues and their function is vital for numerous physiological processes, in particular of neurons and muscle cells. Potentially reversible oxidative regulation of voltage-gated K+ channels by reactive species such as reactive oxygen species (ROS) represents a contributing mechanism of normal cellular plasticity and may play important roles in diverse pathologies including neurodegenerative diseases. Recent Advances: Studies using various protocols of oxidative modification, site-directed mutagenesis, and structural and kinetic modeling provide a broader phenomenology and emerging mechanistic insights. Critical Issues: Physicochemical mechanisms of the functional consequences of oxidative modifications of voltage-gated K+ channels are only beginning to be revealed. In vivo documentation of oxidative modifications of specific amino-acid residues of various voltage-gated K+ channel proteins, including the target specificity issue, is largely absent. Future Directions: High-resolution chemical and proteomic analysis of ion channel proteins with respect to oxidative modification combined with ongoing studies on channel structure and function will provide a better understanding of how the function of voltage-gated K+ channels is tuned by ROS and the corresponding reducing enzymes to meet cellular needs. Antioxid. Redox Signal. 21, 933–952. PMID:24040918

Realistic expectations of prepulse inhibition in translational models for schizophrenia research

PubMed Central

Swerdlow, Neal R.; Weber, Martin; Qu, Ying; Light, Gregory A.; Braff, David L.

2009-01-01

Introduction Under specific conditions, a weak lead stimulus, or “prepulse”, can inhibit the startling effects of a subsequent intense abrupt stimulus. This startle-inhibiting effect of the prepulse, termed “prepulse inhibition” (PPI), is widely used in translational models to understand the biology of brain based inhibitory mechanisms and their deficiency in neuropsychiatric disorders. In 1981, four published reports with “prepulse inhibition” as an index term were listed on Medline; over the past 5 years, new published Medline reports with “prepulse inhibition” as an index term have appeared at a rate exceeding once every 2.7 days (n = 678). Most of these reports focus on the use of PPI in translational models of impaired sensorimotor gating in schizophrenia. This rapid expansion and broad application of PPI as a tool for understanding schizophrenia has, at times, outpaced critical thinking and falsifiable hypotheses about the relative strengths vs. limitations of this measure. Objectives This review enumerates the realistic expectations for PPI in translational models for schizophrenia research, and provides cautionary notes for the future applications of this important research tool. Conclusion In humans, PPI is not “diagnostic”; levels of PPI do not predict clinical course, specific symptoms, or individual medication responses. In preclinical studies, PPI is valuable for evaluating models or model organisms relevant to schizophrenia, “mapping” neural substrates of deficient PPI in schizophrenia, and advancing the discovery and development of novel therapeutics. Across species, PPI is a reliable, robust quantitative phenotype that is useful for probing the neurobiology and genetics of gating deficits in schizophrenia. PMID:18568339

Phosphodiesterase 9A regulates central cGMP and modulates responses to cholinergic and monoaminergic perturbation in vivo.

PubMed

Kleiman, Robin J; Chapin, Douglas S; Christoffersen, Curt; Freeman, Jody; Fonseca, Kari R; Geoghegan, Kieran F; Grimwood, Sarah; Guanowsky, Victor; Hajós, Mihály; Harms, John F; Helal, Christopher J; Hoffmann, William E; Kocan, Geralyn P; Majchrzak, Mark J; McGinnis, Dina; McLean, Stafford; Menniti, Frank S; Nelson, Fredrick; Roof, Robin; Schmidt, Anne W; Seymour, Patricia A; Stephenson, Diane T; Tingley, Francis David; Vanase-Frawley, Michelle; Verhoest, Patrick R; Schmidt, Christopher J

2012-05-01

Cyclic nucleotides are critical regulators of synaptic plasticity and participate in requisite signaling cascades implicated across multiple neurotransmitter systems. Phosphodiesterase 9A (PDE9A) is a high-affinity, cGMP-specific enzyme widely expressed in the rodent central nervous system. In the current study, we observed neuronal staining with antibodies raised against PDE9A protein in human cortex, cerebellum, and subiculum. We have also developed several potent, selective, and brain-penetrant PDE9A inhibitors and used them to probe the function of PDE9A in vivo. Administration of these compounds to animals led to dose-dependent accumulation of cGMP in brain tissue and cerebrospinal fluid, producing a range of biological effects that implied functional significance for PDE9A-regulated cGMP in dopaminergic, cholinergic, and serotonergic neurotransmission and were consistent with the widespread distribution of PDE9A. In vivo effects of PDE9A inhibition included reversal of the respective disruptions of working memory by ketamine, episodic and spatial memory by scopolamine, and auditory gating by amphetamine, as well as potentiation of risperidone-induced improvements in sensorimotor gating and reversal of the stereotypic scratching response to the hallucinogenic 5-hydroxytryptamine 2A agonist mescaline. The results suggested a role for PDE9A in the regulation of monoaminergic circuitry associated with sensory processing and memory. Thus, PDE9A activity regulates neuronal cGMP signaling downstream of multiple neurotransmitter systems, and inhibition of PDE9A may provide therapeutic benefits in psychiatric and neurodegenerative diseases promoted by the dysfunction of these diverse neurotransmitter systems.

Integrating respiratory gating into a megavoltage cone-beam CT system

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

Chang Jenghwa; Sillanpaa, Jussi; Ling, Clifton C.

2006-07-15

We have previously described a low-dose megavoltage cone beam computed tomography (MV CBCT) system capable of producing projection image using one beam pulse. In this study, we report on its integration with respiratory gating for gated radiotherapy. The respiratory gating system tracks a reflective marker on the patient's abdomen midway between the xiphoid and umbilicus, and disables radiation delivery when the marker position is outside predefined thresholds. We investigate two strategies for acquiring gated scans. In the continuous rotation-gated acquisition, the linear accelerator (LINAC) is set to the fixed x-ray mode and the gantry makes a 5 min, 360 deg.continuousmore » rotation, during which the gating system turns the radiation beam on and off, resulting in projection images with an uneven distribution of projection angles (e.g., in 70 arcs each covering 2 deg.). In the gated rotation-continuous acquisition, the LINAC is set to the dynamic arc mode, which suspends the gantry rotation when the gating system inhibits the beam, leading to a slightly longer (6-7 min) scan time, but yielding projection images with more evenly distributed projection angles (e.g., {approx}0.8 deg.between two consecutive projection angles). We have tested both data acquisition schemes on stationary (a contrast detail and a thoracic) phantoms and protocol lung patients. For stationary phantoms, a separate motion phantom not visible in the images is used to trigger the RPM system. Frame rate is adjusted so that approximately 450 images (13 MU) are acquired for each scan and three-dimensional tomographic images reconstructed using a Feldkamp filtered backprojection algorithm. The gated rotation-continuous acquisition yield reconstructions free of breathing artifacts. The tumor in parenchymal lung and normal tissues are easily discernible and the boundary between the diaphragm and the lung sharply defined. Contrast-to-noise ratio (CNR) is not degraded relative to nongated scans of stationary phantoms. The continuous rotation-gated acquisition scan also yields tomographic images with discernible anatomic features; however, streak artifacts are observed and CNR is reduced by approximately a factor of 4. In conclusion, we have successfully developed a gated MV CBCT system to verify the patient positioning for gated radiotherapy.« less

Sensori-Motor and Daily Living Skills of Preschool Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Jasmin, Emmanuelle; Couture, Melanie; McKinley, Patricia; Reid, Greg; Fombonne, Eric; Gisel, Erika

2009-01-01

Sensori-motor development and performance of daily living skills (DLS) remain little explored in children with autism spectrum disorders (ASD). The objective of this study was to determine the impact of sensori-motor skills on the performance of DLS in preschool children with ASD. Thirty-five children, 3-4 years of age, were recruited and assessed…

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

Ahmed, Raef S.; Shen, Sui; Ove, Roger

We wanted to describe a technique for the implementation of intensity-modulated radiotherapy (IMRT) with a real-time position monitor (RPM) respiratory gating system for the treatment of pleural space with intact lung. The technique is illustrated by a case of pediatric osteosarcoma, metastatic to the pleura of the right lung. The patient was simulated in the supine position where a breathing tracer and computed tomography (CT) scans synchronized at end expiration were acquired using the RPM system. The gated CT images were used to define target volumes and critical structures. Right pleural gated IMRT delivered at end expiration was prescribed tomore » a dose of 44 Gy, with 55 Gy delivered to areas of higher risk via simultaneous integrated boost (SIB) technique. IMRT was necessary to avoid exceeding the tolerance of intact lung. Although very good coverage of the target volume was achieved with a shell-shaped dose distribution, dose over the targets was relatively inhomogeneous. Portions of target volumes necessarily intruded into the right lung, the liver, and right kidney, limiting the degree of normal tissue sparing that could be achieved. The radiation doses to critical structures were acceptable and well tolerated. With intact lung, delivering a relatively high dose to the pleura with acceptable doses to surrounding normal tissues using respiratory gated pleural IMRT is feasible. Treatment delivery during a limited part of the respiratory cycle allows for reduced CT target volume motion errors, with reduction in the portion of the planning margin that accounts for respiratory motion, and subsequent increase in the therapeutic ratio.« less

Time-resolved 3D MR velocity mapping at 3T: improved navigator-gated assessment of vascular anatomy and blood flow.

PubMed

Markl, Michael; Harloff, Andreas; Bley, Thorsten A; Zaitsev, Maxim; Jung, Bernd; Weigang, Ernst; Langer, Mathias; Hennig, Jürgen; Frydrychowicz, Alex

2007-04-01

To evaluate an improved image acquisition and data-processing strategy for assessing aortic vascular geometry and 3D blood flow at 3T. In a study with five normal volunteers and seven patients with known aortic pathology, prospectively ECG-gated cine three-dimensional (3D) MR velocity mapping with improved navigator gating, real-time adaptive k-space ordering and dynamic adjustment of the navigator acceptance criteria was performed. In addition to morphological information and three-directional blood flow velocities, phase-contrast (PC)-MRA images were derived from the same data set, which permitted 3D isosurface rendering of vascular boundaries in combination with visualization of blood-flow patterns. Analysis of navigator performance and image quality revealed improved scan efficiencies of 63.6%+/-10.5% and temporal resolution (<50 msec) compared to previous implementations. Semiquantitative evaluation of image quality by three independent observers demonstrated excellent general image appearance with moderate blurring and minor ghosting artifacts. Results from volunteer and patient examinations illustrate the potential of the improved image acquisition and data-processing strategy for identifying normal and pathological blood-flow characteristics. Navigator-gated time-resolved 3D MR velocity mapping at 3T in combination with advanced data processing is a powerful tool for performing detailed assessments of global and local blood-flow characteristics in the aorta to describe or exclude vascular alterations. Copyright (c) 2007 Wiley-Liss, Inc.

Sensorimotor adaptation of speech in Parkinson's disease.

PubMed

Mollaei, Fatemeh; Shiller, Douglas M; Gracco, Vincent L

2013-10-01

The basal ganglia are involved in establishing motor plans for a wide range of behaviors. Parkinson's disease (PD) is a manifestation of basal ganglia dysfunction associated with a deficit in sensorimotor integration and difficulty in acquiring new motor sequences, thereby affecting motor learning. Previous studies of sensorimotor integration and sensorimotor adaptation in PD have focused on limb movements using visual and force-field alterations. Here, we report the results from a sensorimotor adaptation experiment investigating the ability of PD patients to make speech motor adjustments to a constant and predictable auditory feedback manipulation. Participants produced speech while their auditory feedback was altered and maintained in a manner consistent with a change in tongue position. The degree of adaptation was associated with the severity of motor symptoms. The patients with PD exhibited adaptation to the induced sensory error; however, the degree of adaptation was reduced compared with healthy, age-matched control participants. The reduced capacity to adapt to a change in auditory feedback is consistent with reduced gain in the sensorimotor system for speech and with previous studies demonstrating limitations in the adaptation of limb movements after changes in visual feedback among patients with PD. © 2013 Movement Disorder Society.

Using virtual reality to augment perception, enhance sensorimotor adaptation, and change our minds

PubMed Central

Wright, W. Geoffrey

2014-01-01

Technological advances that involve human sensorimotor processes can have both intended and unintended effects on the central nervous system (CNS). This mini review focuses on the use of virtual environments (VE) to augment brain functions by enhancing perception, eliciting automatic motor behavior, and inducing sensorimotor adaptation. VE technology is becoming increasingly prevalent in medical rehabilitation, training simulators, gaming, and entertainment. Although these VE applications have often been shown to optimize outcomes, whether it be to speed recovery, reduce training time, or enhance immersion and enjoyment, there are inherent drawbacks to environments that can potentially change sensorimotor calibration. Across numerous VE studies over the years, we have investigated the effects of combining visual and physical motion on perception, motor control, and adaptation. Recent results from our research involving exposure to dynamic passive motion within a visually-depicted VE reveal that short-term exposure to augmented sensorimotor discordance can result in systematic aftereffects that last beyond the exposure period. Whether these adaptations are advantageous or not, remains to be seen. Benefits as well as risks of using VE-driven sensorimotor stimulation to enhance brain processes will be discussed. PMID:24782724

Defective cerebellar control of cortical plasticity in writer’s cramp

PubMed Central

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

2013-01-01

A large body of evidence points to a role of basal ganglia dysfunction in the pathophysiology of dystonia, but recent studies indicate that cerebellar dysfunction may also be involved. The cerebellum influences sensorimotor adaptation by modulating sensorimotor plasticity of the primary motor cortex. Motor cortex sensorimotor plasticity is maladaptive in patients with writer’s cramp. Here we examined whether putative cerebellar dysfunction in dystonia is linked to these patients’ maladaptive plasticity. To that end we compared the performances of patients and healthy control subjects in a reaching task involving a visuomotor conflict generated by imposing a random deviation (−40° to 40°) on the direction of movement of the mouse/cursor. Such a task is known to involve the cerebellum. We also compared, between patients and healthy control subjects, how the cerebellum modulates the extent and duration of an ongoing sensorimotor plasticity in the motor cortex. The cerebellar cortex was excited or inhibited by means of repeated transcranial magnetic stimulation before artificial sensorimotor plasticity was induced in the motor cortex by paired associative stimulation. Patients with writer’s cramp were slower than the healthy control subjects to reach the target and, after having repeatedly adapted their trajectories to the deviations, they were less efficient than the healthy control subjects to perform reaching movement without imposed deviation. It was interpreted as impaired washing-out abilities. In healthy subjects, cerebellar cortex excitation prevented the paired associative stimulation to induce a sensorimotor plasticity in the primary motor cortex, whereas cerebellar cortex inhibition led the paired associative stimulation to be more efficient in inducing the plasticity. In patients with writer’s cramp, cerebellar cortex excitation and inhibition were both ineffective in modulating sensorimotor plasticity. In patients with writer’s cramp, but not in healthy subjects, behavioural parameters reflecting their capacity for adapting to the rotation and for washing-out of an earlier adaptation predicted the efficacy of inhibitory cerebellar conditioning to influence sensorimotor plasticity: the better the online adaptation, the smaller the influence of cerebellar inhibitory stimulation on motor cortex plasticity. Altered cerebellar encoding of incoming afferent volleys may result in decoupling the motor component from the afferent information flow, and also in maladjusted sensorimotor calibration. The loss of cerebellar control over sensorimotor plasticity might also lead to building up an incorrect motor program to specific adaptation tasks such as writing. PMID:23801734

Hydrophobic interactions between the voltage sensor and pore mediate inactivation in Kv11.1 channels

PubMed Central

Perry, Matthew D.; Wong, Sophia; Ng, Chai Ann

2013-01-01

Kv11.1 channels are critical for the maintenance of a normal heart rhythm. The flow of potassium ions through these channels is controlled by two voltage-regulated gates, termed “activation” and “inactivation,” located at opposite ends of the pore. Crucially in Kv11.1 channels, inactivation gating occurs much more rapidly, and over a distinct range of voltages, compared with activation gating. Although it is clear that the fourth transmembrane segments (S4), within each subunit of the tetrameric channel, are important for controlling the opening and closing of the activation gate, their role during inactivation gating is much less clear. Here, we use rate equilibrium free energy relationship (REFER) analysis to probe the contribution of the S4 “voltage-sensor” helix during inactivation of Kv11.1 channels. Contrary to the important role that charged residues play during activation gating, it is the hydrophobic residues (Leu529, Leu530, Leu532, and Val535) that are the key molecular determinants of inactivation gating. Within the context of an interconnected multi-domain model of Kv11.1 inactivation gating, our REFER analysis indicates that the S4 helix and the S4–S5 linker undergo a conformational rearrangement shortly after that of the S5 helix and S5P linker, but before the S6 helix. Combining REFER analysis with double mutant cycle analysis, we provide evidence for a hydrophobic interaction between residues on the S4 and S5 helices. Based on a Kv11.1 channel homology model, we propose that this hydrophobic interaction forms the basis of an intersubunit coupling between the voltage sensor and pore domain that is an important mediator of inactivation gating. PMID:23980196

Region-specific reduction of auditory sensory gating in older adults.

PubMed

Cheng, Chia-Hsiung; Baillet, Sylvain; Lin, Yung-Yang

2015-12-01

Aging has been associated with declines in sensory-perceptual processes. Sensory gating (SG), or repetition suppression, refers to the attenuation of neural activity in response to a second stimulus and is considered to be an automatic process to inhibit redundant sensory inputs. It is controversial whether SG deficits, as tested with an auditory paired-stimulus protocol, accompany normal aging in humans. To reconcile the debates arising from event-related potential studies, we recorded auditory neuromagnetic reactivity in 20 young and 19 elderly adult men and determined the neural activation by using minimum-norm estimate (MNE) source modeling. SG of M100 was calculated by the ratio of the response to the second stimulus over that to the first stimulus. MNE results revealed that fronto-temporo-parietal networks were implicated in the M100 SG. Compared to the younger participants, the elderly showed selectively increased SG ratios in the anterior superior temporal gyrus, anterior middle temporal gyrus, temporal pole and orbitofrontal cortex, suggesting an insufficient age-related gating to repetitive auditory stimulation. These findings also highlight the loss of frontal inhibition of the auditory cortex in normal aging. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of aortic tortuosity on left ventricular diastolic parameters derived from gated myocardial perfusion single photon emission computed tomography in patients with normal myocardial perfusion.

PubMed

Kurisu, Satoshi; Nitta, Kazuhiro; Sumimoto, Yoji; Ikenaga, Hiroki; Ishibashi, Ken; Fukuda, Yukihiro; Kihara, Yasuki

2018-06-01

Aortic tortuosity is often found on chest radiograph, especially in aged patients. We tested the hypothesis that aortic tortuosity was associated with LV diastolic parameters derived from gated SPECT in patients with normal myocardial perfusion. One-hundred and twenty-two patients with preserved LV ejection fraction and normal myocardial perfusion were enrolled. Descending aortic deviation was defined as the horizontal distance from the left line of the aortic knob to the most prominent left line of the descending aorta. This parameter was measured for the quantitative assessment of aortic tortuosity. Peak filling rate (PFR) and one-third mean filling rate (1/3 MFR) were obtained from redistribution images as LV diastolic parameters. Descending aortic deviation ranged from 0 to 22 mm with a mean distance of 4.5 ± 6.3 mm. Descending aortic deviation was significantly correlated with age (r = 0.38, p < 0.001) and estimated glomerular filtration rate (eGFR) (r = - 0.21, p = 0.02). Multivariate linear regression analysis revealed that eGFR (β = 0.23, p = 0.02) and descending aortic deviation (β = - 0.23, p = 0.01) were significantly associated with PFR, and that only descending aortic deviation (β = - 0.21, p = 0.03) was significantly associated with 1/3 MFR. Our data suggest that aortic tortuosity is associated with LV diastolic parameters derived from gated SPECT in patients with normal myocardial perfusion.

Catching-up: Children with developmental coordination disorder compared to healthy children before and after sensorimotor therapy

PubMed Central

2017-01-01

The aims of the present study were to (a) compare healthy children in terms of sensorimotor maturity to untreated children diagnosed with developmental coordination disorder (DCD) and (b) compare healthy children to diagnosed children following completed treatment with sensorimotor therapy. Participants were 298 children, 196 boys and 102 girls, distributed into a Norm group of healthy children (n = 99) and a group of children diagnosed with DCD (n = 199) with a total mean age of 8.77 years (SD = 2.88). Participants in both groups were assessed on instruments aimed to detect sensorimotor deviations. The children in the DCD group completed, during on average 36 months, sensorimotor therapy which comprised stereotypical fetal- and infant movements, vestibular stimulation, tactile stimulation, auditory stimulation, complementary play exercises, gross motor milestones, and sports-related gross motor skills. At the final visit a full assessment was once more performed. Results showed that the Norm group performed better on all sensorimotor tests as compared to the untreated children from the DCD group, with the exception of an audiometric test where both groups performed at the same level. Girls performed better on tests assessing proprioceptive and balance abilities. Results also showed, after controls for natural maturing effects, that the children from the DCD group after sensorimotor therapy did catch up with the healthy children. The concept of “catching-up” is used within developmental medicine but has not earlier been documented with regard to children and youth in connection with DCD. PMID:29020061

Relationships between regional cerebellar volume and sensorimotor and cognitive function in young and older adults

PubMed Central

Bernard, Jessica A.; Seidler, Rachael D.

2013-01-01

The cerebellum has been implicated in both sensorimotor and cognitive function, but is known to undergo volumetric declines with advanced age. Individual differences in regional cerebellar volume may therefore provide insight into performance variability across the lifespan, as has been shown with other brain structures and behaviors. Here, we investigated whether there are regional age differences in cerebellar volume in young and older adults, and whether these volumes explain, in part, individual differences in sensorimotor and cognitive task performance. We found that older adults had smaller cerebellar volume than young adults; specifically, lobules in the anterior cerebellum were more impacted by age. Multiple regression analyses for both age groups revealed associations between sensorimotor task performance in several domains (balance, choice reaction time, and timing) and regional cerebellar volume. There were also relationships with working memory, but none with measures of general cognitive or executive function. Follow-up analyses revealed several differential relationships with age between regional volume and sensorimotor performance. These relationships were predominantly selective to cerebellar regions that have been implicated in cognitive functions. Therefore, it may be the cognitive aspects of sensorimotor task performance that are best explained by individual differences in regional cerebellar volumes. In sum, our results demonstrate the importance of regional cerebellar volume with respect to both sensorimotor and cognitive performance, and we provide additional insight into the role of the cerebellum in age-related performance declines. PMID:23625382

Genetic Circuit Performance under Conditions Relevant for Industrial Bioreactors

PubMed Central

Moser, Felix; Broers, Nicolette J.; Hartmans, Sybe; Tamsir, Alvin; Kerkman, Richard; Roubos, Johannes A.; Bovenberg, Roel; Voigt, Christopher A.

2014-01-01

Synthetic genetic programs promise to enable novel applications in industrial processes. For such applications, the genetic circuits that compose programs will require fidelity in varying and complex environments. In this work, we report the performance of two synthetic circuits in Escherichia coli under industrially relevant conditions, including the selection of media, strain, and growth rate. We test and compare two transcriptional circuits: an AND and a NOR gate. In E. coli DH10B, the AND gate is inactive in minimal media; activity can be rescued by supplementing the media and transferring the gate into the industrial strain E. coli DS68637 where normal function is observed in minimal media. In contrast, the NOR gate is robust to media composition and functions similarly in both strains. The AND gate is evaluated at three stages of early scale-up: 100 ml shake-flask experiments, a 1 ml MTP microreactor, and a 10 L bioreactor. A reference plasmid that constitutively produces a GFP reporter is used to make comparisons of circuit performance across conditions. The AND gate function is quantitatively different at each scale. The output deteriorates late in fermentation after the shift from exponential to constant feed rates, which induces rapid resource depletion and changes in growth rate. In addition, one of the output states of the AND gate failed in the bioreactor, effectively making it only responsive to a single input. Finally, cells carrying the AND gate show considerably less accumulation of biomass. Overall, these results highlight challenges and suggest modified strategies for developing and characterizing genetic circuits that function reliably during fermentation. PMID:23656232

Validation of the Spatial Accuracy of the ExacTracRTM Adaptive Gating System

NASA Astrophysics Data System (ADS)

Twork, Gregory

Stereotactic body radiation therapy (SBRT) is a method of treatment that is used in extracranial locations, including the abdominal and thoracic cavities, as well as spinal and paraspinal locations. At the McGill University Health Centre, liver SBRT treatments include gating, which places the treatment beam on a duty cycle controlled by tracking of fiducial markers moving with the patient's breathing cycle. Respiratory gated treatments aim to spare normal tissue, while delivering a dose properly to a moving target. The ExacTracRTM system (BrainLAB AG Germany) is an image-guided radiotherapy system consisting of a combination of infra-red (IR) cameras and dual kilovoltage (kV) X-ray tubes. The IR system is used to track patient positioning and respiratory motion, while the kV X-rays are used to determine a positional shift based on internal anatomy or fiducial markers. In order to validate the system's ability to treat under gating conditions, each step of the SBRT process was evaluated quantitatively. Initially the system was tested under ideal static conditions, followed by a study including gated parameters. The uncertainties of the isocenters, positioning algorithm, planning computed tomography (CT) and four dimensional CT (4DCT) scans, gating window size and tumor motion were evaluated for their contributions to the total uncertainty in treatment. The mechanical isocenter and 4DCT were found to be the largest sources of uncertainty. However, for tumors with large internal amplitudes (>2.25 cm) that are treated with large gating windows (>30%) the gating parameters can contribute more than 1.1 +/- 1.8 mm.

Sensory Gating and Alpha-7 Nicotinic Receptor Gene Allelic Variants in Schizoaffective Disorder, Bipolar Type

PubMed Central

Martin, Laura F.; Leonard, Sherry; Hall, Mei-Hua; Tregellas, Jason R.; Freedman, Robert; Olincy, Ann

2011-01-01

Objectives Single nucleotide allelic variants in the promoter region of the chromosome 15 alpha-7 acetylcholine nicotinic receptor gene (CHRNA7) are associated with both schizophrenia and the P50 auditory evoked potential sensory gating deficit. The purpose of this study was to determine if CHRNA7 promoter allelic variants are also associated with abnormal P50 ratios in persons with schizoaffective disorder, bipolar type. Methods P50 auditory evoked potentials were recorded in a paired stimulus paradigm in 17 subjects with schizoaffective disorder, bipolar type. The P50 test to conditioning ratio was used as the measure of sensory gating. Mutation screening of the CHRNA7 promoter region was performed on the subjects’ DNA samples. Comparisons to previously obtained data from persons with schizophrenia and controls were made. Results Subjects with schizophrenia, regardless of allele status, had an abnormal mean P50 ratio. Subjects with schizoaffective disorder, bipolar type and a variant allele had an abnormal mean P50 ratio, whereas those schizoaffective subjects with the common alleles had a normal mean P50 ratio. Normal control subjects had a normal mean ratio, but controls with variant alleles had higher P50 ratios. Conclusions In persons with bipolar type schizoaffective disorder, CHRNA7 promoter region allelic variants are linked to the capacity to inhibit the P50 auditory evoked potential and thus are associated with a type of illness genetically and biologically more similar to schizophrenia. PMID:17192894

Comparison of Gated Audiovisual Speech Identification in Elderly Hearing Aid Users and Elderly Normal-Hearing Individuals

PubMed Central

Lidestam, Björn; Rönnberg, Jerker

2016-01-01

The present study compared elderly hearing aid (EHA) users (n = 20) with elderly normal-hearing (ENH) listeners (n = 20) in terms of isolation points (IPs, the shortest time required for correct identification of a speech stimulus) and accuracy of audiovisual gated speech stimuli (consonants, words, and final words in highly and less predictable sentences) presented in silence. In addition, we compared the IPs of audiovisual speech stimuli from the present study with auditory ones extracted from a previous study, to determine the impact of the addition of visual cues. Both participant groups achieved ceiling levels in terms of accuracy in the audiovisual identification of gated speech stimuli; however, the EHA group needed longer IPs for the audiovisual identification of consonants and words. The benefit of adding visual cues to auditory speech stimuli was more evident in the EHA group, as audiovisual presentation significantly shortened the IPs for consonants, words, and final words in less predictable sentences; in the ENH group, audiovisual presentation only shortened the IPs for consonants and words. In conclusion, although the audiovisual benefit was greater for EHA group, this group had inferior performance compared with the ENH group in terms of IPs when supportive semantic context was lacking. Consequently, EHA users needed the initial part of the audiovisual speech signal to be longer than did their counterparts with normal hearing to reach the same level of accuracy in the absence of a semantic context. PMID:27317667

Continuous Three-Dimensional Control of a Virtual Helicopter Using a Motor Imagery Based Brain-Computer Interface

PubMed Central

Doud, Alexander J.; Lucas, John P.; Pisansky, Marc T.; He, Bin

2011-01-01

Brain-computer interfaces (BCIs) allow a user to interact with a computer system using thought. However, only recently have devices capable of providing sophisticated multi-dimensional control been achieved non-invasively. A major goal for non-invasive BCI systems has been to provide continuous, intuitive, and accurate control, while retaining a high level of user autonomy. By employing electroencephalography (EEG) to record and decode sensorimotor rhythms (SMRs) induced from motor imaginations, a consistent, user-specific control signal may be characterized. Utilizing a novel method of interactive and continuous control, we trained three normal subjects to modulate their SMRs to achieve three-dimensional movement of a virtual helicopter that is fast, accurate, and continuous. In this system, the virtual helicopter's forward-backward translation and elevation controls were actuated through the modulation of sensorimotor rhythms that were converted to forces applied to the virtual helicopter at every simulation time step, and the helicopter's angle of left or right rotation was linearly mapped, with higher resolution, from sensorimotor rhythms associated with other motor imaginations. These different resolutions of control allow for interplay between general intent actuation and fine control as is seen in the gross and fine movements of the arm and hand. Subjects controlled the helicopter with the goal of flying through rings (targets) randomly positioned and oriented in a three-dimensional space. The subjects flew through rings continuously, acquiring as many as 11 consecutive rings within a five-minute period. In total, the study group successfully acquired over 85% of presented targets. These results affirm the effective, three-dimensional control of our motor imagery based BCI system, and suggest its potential applications in biological navigation, neuroprosthetics, and other applications. PMID:22046274

Natural biological variation of white matter microstructure is accentuated in Huntington's disease.

PubMed

Gregory, Sarah; Crawford, Helen; Seunarine, Kiran; Leavitt, Blair; Durr, Alexandra; Roos, Raymund A C; Scahill, Rachael I; Tabrizi, Sarah J; Rees, Geraint; Langbehn, Douglas; Orth, Michael

2018-04-22

Huntington's disease (HD) is a monogenic neurodegenerative disorder caused by a CAG-repeat expansion in the Huntingtin gene. Presence of this expansion signifies certainty of disease onset, but only partly explains age at which onset occurs. Genome-wide association studies have shown that naturally occurring genetic variability influences HD pathogenesis and disease onset. Investigating the influence of biological traits in the normal population, such as variability in white matter properties, on HD pathogenesis could provide a complementary approach to understanding disease modification. We have previously shown that while white matter diffusivity patterns in the left sensorimotor network were similar in controls and HD gene-carriers, they were more extreme in the HD group. We hypothesized that the influence of natural variation in diffusivity on effects of HD pathogenesis on white matter is not limited to the sensorimotor network but extends to cognitive, limbic, and visual networks. Using tractography, we investigated 32 bilateral pathways within HD-related networks, including motor, cognitive, and limbic, and examined diffusivity metrics using principal components analysis. We identified three independent patterns of diffusivity common to controls and HD gene-carriers that predicted HD status. The first pattern involved almost all tracts, the second was limited to sensorimotor tracts, and the third encompassed cognitive network tracts. Each diffusivity pattern was associated with network specific performance. The consistency in diffusivity patterns across both groups coupled with their association with disease status and task performance indicates that naturally-occurring patterns of diffusivity can become accentuated in the presence of the HD gene mutation to influence clinical brain function. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Quantitative measures detect sensory and motor impairments in multiple sclerosis.

PubMed

Newsome, Scott D; Wang, Joseph I; Kang, Jonathan Y; Calabresi, Peter A; Zackowski, Kathleen M

2011-06-15

Sensory and motor dysfunction in multiple sclerosis (MS) is often assessed with rating scales which rely heavily on clinical judgment. Quantitative devices may be more precise than rating scales. To quantify lower extremity sensorimotor measures in individuals with MS, evaluate the extent to which they can detect functional systems impairments, and determine their relationship to global disability measures. We tested 145 MS subjects and 58 controls. Vibration thresholds were quantified using a Vibratron-II device. Strength was quantified by a hand-held dynamometer. We also recorded Expanded Disability Status Scale (EDSS) and Timed 25-Foot Walk (T25FW). t-tests and Wilcoxon-rank sum were used to compare group data. Spearman correlations were used to assess relationships between each measure. We also used a step-wise linear regression model to determine how much the quantitative measures explain the variance in the respective functional systems scores (FSS). EDSS scores ranged from 0-7.5, mean disease duration was 10.4 ± 9.6 years, and 66% were female. In relapsing-remitting MS, but not progressive MS, poorer vibration sensation correlated with a worse EDSS score, whereas progressive groups' ankle/hip strength changed significantly with EDSS progression. Interestingly, not only did sensorimotor measures significantly correlate with global disability measures (i.e., EDSS), but they had improved sensitivity, as they detected impairments in up to 32% of MS subjects with normal sensory and pyramidal FSS. Sensory and motor deficits in MS can be quantified using clinically accessible tools and distinguish differences among MS subtypes. We show that quantitative sensorimotor measures are more sensitive than FSS from the EDSS. These tools have the potential to be used as clinical outcome measures in practice and for future MS clinical trials of neurorehabilitative and neuroreparative interventions. Copyright © 2011 Elsevier B.V. All rights reserved.

Augmentation-related brain plasticity

PubMed Central

Di Pino, Giovanni; Maravita, Angelo; Zollo, Loredana; Guglielmelli, Eugenio; Di Lazzaro, Vincenzo

2014-01-01

Today, the anthropomorphism of the tools and the development of neural interfaces require reconsidering the concept of human-tools interaction in the framework of human augmentation. This review analyses the plastic process that the brain undergoes when it comes into contact with augmenting artificial sensors and effectors and, on the other hand, the changes that the use of external augmenting devices produces in the brain. Hitherto, few studies investigated the neural correlates of augmentation, but clues on it can be borrowed from logically-related paradigms: sensorimotor training, cognitive enhancement, cross-modal plasticity, sensorimotor functional substitution, use and embodiment of tools. Augmentation modifies function and structure of a number of areas, i.e., primary sensory cortices shape their receptive fields to become sensitive to novel inputs. Motor areas adapt the neuroprosthesis representation firing-rate to refine kinematics. As for normal motor outputs, the learning process recruits motor and premotor cortices and the acquisition of proficiency decreases attentional recruitment, focuses the activity on sensorimotor areas and increases the basal ganglia drive on the cortex. Augmentation deeply relies on the frontoparietal network. In particular, premotor cortex is involved in learning the control of an external effector and owns the tool motor representation, while the intraparietal sulcus extracts its visual features. In these areas, multisensory integration neurons enlarge their receptive fields to embody supernumerary limbs. For operating an anthropomorphic neuroprosthesis, the mirror system is required to understand the meaning of the action, the cerebellum for the formation of its internal model and the insula for its interoception. In conclusion, anthropomorphic sensorized devices can provide the critical sensory afferences to evolve the exploitation of tools through their embodiment, reshaping the body representation and the sense of the self. PMID:24966816

Quantitative measures detect sensory and motor impairments in multiple sclerosis

PubMed Central

Newsome, Scott D.; Wang, Joseph I.; Kang, Jonathan Y.; Calabresi, Peter A.; Zackowski, Kathleen M.

2011-01-01

Background Sensory and motor dysfunction in multiple sclerosis (MS) is often assessed with rating scales which rely heavily on clinical judgment. Quantitative devices may be more precise than rating scales. Objective To quantify lower extremity sensorimotor measures in individuals with MS, evaluate the extent to which they can detect functional systems impairments, and determine their relationship to global disability measures. Methods We tested 145 MS subjects and 58 controls. Vibration thresholds were quantified using a Vibratron-II device. Strength was quantified by a hand-held dynamometer. We also recorded Expanded Disability Status Scale (EDSS) and timed 25-foot walk (T25FW). T-tests and Wilcoxon-rank sum were used to compare group data. Spearman correlations were used to assess relationships between each measure. We also used a step-wise linear regression model to determine how much the quantitative measures explain the variance in the respective functional systems scores (FSS). Results EDSS scores ranged from 0-7.5, mean disease duration was 10.4±9.6 years, and 66% were female. In RRMS, but not progressive MS, poorer vibration sensation correlated with a worse EDSS score, whereas progressive groups’ ankle/hip strength changed significantly with EDSS progression. Interestingly, not only did sensorimotor measures significantly correlate with global disability measures (EDSS), but they had improved sensitivity, as they detected impairments in up to 32% of MS subjects with normal sensory FSS. Conclusions Sensory and motor deficits can be quantified using clinically accessible tools and distinguish differences among MS subtypes. We show that quantitative sensorimotor measures are more sensitive than FSS from the EDSS. These tools have the potential to be used as clinical outcome measures in practice and for future MS clinical trials of neurorehabilitative and neuroreparative interventions. PMID:21458828

Fabry-Pérot Interference in Gapped Bilayer Graphene with Broken Anti-Klein Tunneling

NASA Astrophysics Data System (ADS)

Varlet, Anastasia; Liu, Ming-Hao; Krueckl, Viktor; Bischoff, Dominik; Simonet, Pauline; Watanabe, Kenji; Taniguchi, Takashi; Richter, Klaus; Ensslin, Klaus; Ihn, Thomas

2014-09-01

We report the experimental observation of Fabry-Pérot interference in the conductance of a gate-defined cavity in a dual-gated bilayer graphene device. The high quality of the bilayer graphene flake, combined with the device's electrical robustness provided by the encapsulation between two hexagonal boron nitride layers, allows us to observe ballistic phase-coherent transport through a 1-μm-long cavity. We confirm the origin of the observed interference pattern by comparing to tight-binding calculations accounting for the gate-tunable band gap. The good agreement between experiment and theory, free of tuning parameters, further verifies that a gap opens in our device. The gap is shown to destroy the perfect reflection for electrons traversing the barrier with normal incidence (anti-Klein tunneling). The broken anti-Klein tunneling implies that the Berry phase, which is found to vary with the gate voltages, is always involved in the Fabry-Pérot oscillations regardless of the magnetic field, in sharp contrast with single-layer graphene.

The sensorimotor and social sides of the architecture of speech.

PubMed

Pezzulo, Giovanni; Barca, Laura; D'Ausilio, Alessando

2014-12-01

Speech is a complex skill to master. In addition to sophisticated phono-articulatory abilities, speech acquisition requires neuronal systems configured for vocal learning, with adaptable sensorimotor maps that couple heard speech sounds with motor programs for speech production; imitation and self-imitation mechanisms that can train the sensorimotor maps to reproduce heard speech sounds; and a "pedagogical" learning environment that supports tutor learning.

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

PubMed Central

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

2012-01-01

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

Changes of the directional brain networks related with brain plasticity in patients with long-term unilateral sensorineural hearing loss.

PubMed

Zhang, G-Y; Yang, M; Liu, B; Huang, Z-C; Li, J; Chen, J-Y; Chen, H; Zhang, P-P; Liu, L-J; Wang, J; Teng, G-J

2016-01-28

Previous studies often report that early auditory deprivation or congenital deafness contributes to cross-modal reorganization in the auditory-deprived cortex, and this cross-modal reorganization limits clinical benefit from cochlear prosthetics. However, there are inconsistencies among study results on cortical reorganization in those subjects with long-term unilateral sensorineural hearing loss (USNHL). It is also unclear whether there exists a similar cross-modal plasticity of the auditory cortex for acquired monaural deafness and early or congenital deafness. To address this issue, we constructed the directional brain functional networks based on entropy connectivity of resting-state functional MRI and researched changes of the networks. Thirty-four long-term USNHL individuals and seventeen normally hearing individuals participated in the test, and all USNHL patients had acquired deafness. We found that certain brain regions of the sensorimotor and visual networks presented enhanced synchronous output entropy connectivity with the left primary auditory cortex in the left long-term USNHL individuals as compared with normally hearing individuals. Especially, the left USNHL showed more significant changes of entropy connectivity than the right USNHL. No significant plastic changes were observed in the right USNHL. Our results indicate that the left primary auditory cortex (non-auditory-deprived cortex) in patients with left USNHL has been reorganized by visual and sensorimotor modalities through cross-modal plasticity. Furthermore, the cross-modal reorganization also alters the directional brain functional networks. The auditory deprivation from the left or right side generates different influences on the human brain. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Modulation transfer function of partial gating detector by liquid crystal auto-controlling light intensity

NASA Astrophysics Data System (ADS)

Yang, Xusan; Tang, Yuanhe; Liu, Kai; Liu, Hanchen; Gao, Haiyang; Li, Qing; Zhang, Ruixia; Ye, Na; Liang, Yuan; Zhao, Gaoxiang

2008-12-01

Based on the electro-optical properties of liquid crystal, we have designed a novel partial gating detector. Liquid crystal can be taken to change its own transmission according to the light intensity outside. Every single pixel of the image is real-time modulated by liquid crystal, thus the strong light is weakened and low light goes through the detector normally .The purpose of partial-gating strong light (>105lx) can be achieved by this detector. The modulation transfer function (MTF) equations of the main optical sub-systems are calculated in this paper, they are liquid crystal panels, linear fiber panel and CCD array detector. According to the relevant size, the MTF value of this system is fitted out. The result is MTF= 0.518 at Nyquist frequency.

Effect of streptozotocin-induced diabetes on left ventricular function in adult rats: an in vivo Pinhole Gated SPECT study

PubMed Central

Cosyns, Bernard; Droogmans, Steven; Weytjens, Caroline; Lahoutte, Tony; Van Camp, Guy; Schoors, Danny; Franken, Philippe R

2007-01-01

Background Recent studies have suggested that diabetes mellitus (DM) may cause left ventricular (LV) dysfunction directly resulting in increased susceptibility to heart failure. Using pinhole collimators and advances in data processing, gated SPECT was recently adapted to image the rat heart. The present study was aimed to assess this new imaging technique for quantifying LV function and remodeling from the Streptozotocin (STZ) rat model compared to controls. Methods Twenty one rats were randomly assigned to control or diabetic group. Six months after the induction of diabetes by STZ, Pinhole 99 m Tc-sestamibi gated SPECT was performed for determining rat LV volumes and function. Post-mortem histopathologic analysis was performed to evaluate the determinant of LV remodeling in this model. Results After six months, the normalized to body weight LV End-systolic volume was significantly different in diabetic rats compared to controls (0.46 ± 0.02 vs 0.33 ± 0.03 μL/g; p = 0.01). The normalized LV End-diastolic volume was also different in both groups (1.51 ± 0.03 vs 0.88 ± 0.05 μL/g; p = 0.001) and the normalized stroke volume was significantly higher in STZ-rats (1.05 ± 0.02 vs 0.54 ± 0.06 μL/g; p = 0.001). The muscular fibers were thinner at histology in the diabetic rats (0.44 ± 0.07 vs 0.32 ± 0.06 AU; p = 0.01). Conclusion Pinhole 99 m Tc-sestamibi gated SPECT can successfully be applied for the evaluation of cardiac function and remodeling in STZ-induced diabetic rats. In this model, LV volumes were significantly changed compared to a control population, leading to a LV dysfunction. These findings were consistent with the histopathological abnormalities. Finally, these data further suggest the presence of diabetes cardiomyopathy. PMID:17937784

Normal myocardial perfusion scan portends a benign prognosis independent from the pretest probability of coronary artery disease. Sub-analysis of the J-ACCESS study.

PubMed

Imamura, Yosihiro; Fukuyama, Takaya; Nishimura, Sigeyuki; Nishimura, Tsunehiko

2009-08-01

We assessed the usefulness of gated stress/rest 99mTc-tetrofosmin myocardial perfusion single photon emission computed tomography (SPECT) to predict ischemic cardiac events in Japanese patients with various estimated pretest probabilities of coronary artery disease (CAD). Of the 4031 consecutively registered patients for a J-ACCESS (Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT) study, 1904 patients without prior cardiac events were selected. Gated stress/rest myocardial perfusion SPECT was performed and segmental perfusion scores and quantitative gated SPECT results were derived. The pretest probability for having CAD was estimated using the American College of Cardiology/American Heart Association/American College of Physicians-American Society of Internal Medicine guideline data for the management of patients with chronic stable angina, which includes age, gender, and type of chest discomfort. The patients were followed up for three years. During the three-year follow-up period, 96 developed ischemic cardiac events: 17 cardiac deaths, 8 nonfatal myocardial infarction, and 71 clinically driven revascularization. The summed stress score (SSS) was the most powerful independent predictor of all ischemic cardiac events (hazard ratio 1.077, CI 1.045-1.110). Abnormal SSS (> 3) was associated with a significantly higher cardiac event rate in patients with an intermediate to high pretest probability of CAD. Normal SSS (< or = 3) was associated with a low event rate in patients with any pretest probability of CAD. Myocardial perfusion SPECT is useful for further risk-stratification of patients with suspected CAD. The abnormal scan result (SSS > 3) is discriminative for subsequent cardiac events only in the groups with an intermediate to high pretest probability of CAD. The salient result is that normal scan results portend a benign prognosis independent from the pretest probability of CAD.

Sensory gating deficits in parents of schizophrenics

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

Waldo, M.; Madison, A.; Freedman, R.

1995-12-18

Although schizophrenia clusters in families, it is not inherited in Mendelian fashion. This suggests that there may be alternative phenotypic expressions of genes that convey risk for schizophrenia, such as more elementary physiological or biochemical defects. One proposed phenotype is impaired inhibitory gating of the auditory evoked potential to repeated stimuli. Normally, the amplitude of the P50 response to the second stimulus is significantly less than the response to the first, but this gating of response is generally impaired in schizophrenia. Clinically unaffected individuals within a pedigree who have both an ancestral and descendant history of schizophrenia may be usefulmore » for studying whether this physiological defect is a possible alternative phenotype. We have studied inhibitory gating of the auditory P50 response to pairs of auditory stimuli in 17 nuclear families. In 11, there was one parent who had another relative with a chronic psychotic illness, in addition to the schizophrenic proband. AR of the parents with family histories of schizophrenia had gating of the P50 response similar to their schizophrenia offspring, whereas only 7% of the parents without family history had gating of the P50 response in the abnormal range. These results support loss of gating of the auditory P50 wave as an inherited deficit related to schizophrenia and suggest that studies of parents may help elucidate the neurobiological expression of genes that convey risk for schizophrenia. 36 refs., 2 figs., 2 tabs.« less

The Contribution of the Parietal Lobes to Speaking and Writing

PubMed Central

Wise, Richard J. S.

2010-01-01

The left parietal lobe has been proposed as a major language area. However, parietal cortical function is more usually considered in terms of the control of actions, contributing both to attention and cross-modal integration of external and reafferent sensory cues. We used positron emission tomography to study normal subjects while they overtly generated narratives, both spoken and written. The purpose was to identify the parietal contribution to the modality-specific sensorimotor control of communication, separate from amodal linguistic and memory processes involved in generating a narrative. The majority of left and right parietal activity was associated with the execution of writing under visual and somatosensory control irrespective of whether the output was a narrative or repetitive reproduction of a single grapheme. In contrast, action-related parietal activity during speech production was confined to primary somatosensory cortex. The only parietal area with a pattern of activity compatible with an amodal central role in communication was the ventral part of the left angular gyrus (AG). The results of this study indicate that the cognitive processing of language within the parietal lobe is confined to the AG and that the major contribution of parietal cortex to communication is in the sensorimotor control of writing. PMID:19531538

Vestibulospinal adaptation to microgravity

NASA Technical Reports Server (NTRS)

Paloski, W. H.

1998-01-01

Human balance control is known to be transiently disrupted after spaceflight; however, the mechanisms responsible for postflight postural ataxia are still under investigation. In this report, we propose a conceptual model of vestibulospinal adaptation based on theoretical adaptive control concepts and supported by the results from a comprehensive study of balance control recovery after spaceflight. The conceptual model predicts that immediately after spaceflight the balance control system of a returning astronaut does not expect to receive gravity-induced afferent inputs and that descending vestibulospinal control of balance is disrupted until the central nervous system is able to cope with the newly available vestibular otolith information. Predictions of the model are tested using data from a study of the neurosensory control of balance in astronauts immediately after landing. In that study, the mechanisms of sensorimotor balance control were assessed under normal, reduced, and/or altered (sway-referenced) visual and somatosensory input conditions. We conclude that the adaptive control model accurately describes the neurobehavioral responses to spaceflight and that similar models of altered sensory, motor, or environmental constraints are needed clinically to predict responses that patients with sensorimotor pathologies may have to various visual-vestibular or changing stimulus environments.

Contribution of Cerebellar Sensorimotor Adaptation to Hippocampal Spatial Memory

PubMed Central

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

2012-01-01

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

Picturing words? Sensorimotor cortex activation for printed words in child and adult readers

PubMed Central

Dekker, Tessa M.; Mareschal, Denis; Johnson, Mark H.; Sereno, Martin I.

2014-01-01

Learning to read involves associating abstract visual shapes with familiar meanings. Embodiment theories suggest that word meaning is at least partially represented in distributed sensorimotor networks in the brain (Barsalou, 2008; Pulvermueller, 2013). We explored how reading comprehension develops by tracking when and how printed words start activating these “semantic” sensorimotor representations as children learn to read. Adults and children aged 7–10 years showed clear category-specific cortical specialization for tool versus animal pictures during a one-back categorisation task. Thus, sensorimotor representations for these categories were in place at all ages. However, co-activation of these same brain regions by the visual objects’ written names was only present in adults, even though all children could read and comprehend all presented words, showed adult-like task performance, and older children were proficient readers. It thus takes years of training and expert reading skill before spontaneous processing of printed words’ sensorimotor meanings develops in childhood. PMID:25463817

A procedure to detect abnormal sensorimotor control in adolescents with idiopathic scoliosis.

PubMed

Pialasse, Jean-Philippe; Mercier, Pierre; Descarreaux, Martin; Simoneau, Martin

2017-09-01

This work identifies, among adolescents with idiopathic scoliosis, those demonstrating impaired sensorimotor control through a classification procedure comparing the amplitude of their vestibular-evoked postural responses. The sensorimotor control of healthy adolescents (n=17) and adolescents with idiopathic scoliosis (n=52) with either mild (Cobb angle≥15° and ≤30°) or severe (Cobb angle >30°) spine deformation was assessed through galvanic vestibular stimulation. A classification procedure sorted out adolescents with idiopathic scoliosis whether the amplitude of their vestibular-evoked postural response was dissimilar or similar to controls. Compared to controls, galvanic vestibular stimulation evoked larger postural response in adolescents with idiopathic scoliosis. Nonetheless, the classification procedure revealed that only 42.5% of all patients showed impaired sensorimotor control. Consequently, identifying patients with sensorimotor control impairment would allow to apply personalized treatments, help clinicians to establish prognosis and hopefully improve the condition of patients with adolescent idiopathic scoliosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Symmetry of fMRI activation in the primary sensorimotor cortex during unilateral chewing.

PubMed

Lotze, M; Domin, M; Kordass, B

2017-05-01

Functional magnetic resonance imaging (fMRI) is one of the most advanced techniques to analyze the cerebral effects on many behavior aspects of the oral system such as chewing and mastication. Studies on imaging of the cerebral representation of chewing demonstrated differential results with respect to cortical lateralization during unilateral chewing. The aim of our study is to clarify the effects of cerebral responses during unilateral chewing. We used fMRI to compare brain activities during occlusal function in centric occlusion on natural teeth and chewing on a gum located on the right or the left teeth in 15 healthy subjects. Group data were performed by Talairach normalization and in addition by an assignment of activation maxima to individual anatomical landmarks in order to avoid possible loss of spatial preciseness of activation sites by normalization procedures. Evaluation of group data by Talairach normalization revealed representation sites for occlusal movements in bilateral primary (S1) and secondary (S2) somatosensory cortices, primary motor (M1) and premotor cortices, supplementary motor area (SMA) and medial cingulate gyrus, bilateral anterior cerebellar hemispheres and vermis, insula, orbitofrontal cortex, thalamus, and left pallidum. Right-sided chewing showed no differential activation to left-sided chewing, and both showed activation in areas also involved in bilateral occlusion. Both techniques, the one based on group normalization and the one based on an individual evaluation method, revealed remarkable low differences in activation maximum location in the primary motor, the primary and secondary somatosensory cortices, and the anterior cerebellar lobe. All chewing movements tested involved bilateral sensorimotor activation without a significant lateralization of activation intensities. Overall, a general lateralization of occlusion movements to the dominant side could not be verified in the present study. Chewing on the left or on the right side of teeth makes no difference for brain representation of chewing. The results describe the basic effects of what we can expect by evaluation of cerebral effects of chewing and mastication. Based on these results, clinical fMRI studies can be performed in different patient groups.

Assessment of regional lung functional impairment with co-registered respiratory-gated ventilation/perfusion SPET-CT images: initial experiences.

PubMed

Suga, Kazuyoshi; Yasuhiko, Kawakami; Zaki, Mohammed; Yamashita, Tomio; Seto, Aska; Matsumoto, Tsuneo; Matsunaga, Naofumi

2004-02-01

In this study, respiratory-gated ventilation and perfusion single-photon emission tomography (SPET) were used to define regional functional impairment and to obtain reliable co-registration with computed tomography (CT) images in various lung diseases. Using a triple-headed SPET unit and a physiological synchroniser, gated perfusion SPET was performed in a total of 78 patients with different pulmonary diseases, including metastatic nodules (n = 15); in 34 of these patients, it was performed in combination with gated technetium-99m Technegas SPET. Projection data were acquired using 60 stops over 120 degrees for each detector. Gated end-inspiration and ungated images were reconstructed from 1/8 data centered at peak inspiration for each regular respiratory cycle and full respiratory cycle data, respectively. Gated images were registered with tidal inspiration CT images using automated three-dimensional (3D) registration software. Registration mismatch was assessed by measuring 3D distance of the centroid of the nine selected round perfusion-defective nodules. Gated SPET images were completed within 29 min, and increased the number of visible ventilation and perfusion defects by 9.7% and 17.2%, respectively, as compared with ungated images; furthermore, lesion-to-normal lung contrast was significantly higher on gated SPET images. In the nine round perfusion-defective nodules, gated images yielded a significantly better SPET-CT match compared with ungated images (4.9 +/- 3.1 mm vs 19.0 +/- 9.1 mm, P<0.001). The co-registered SPET-CT images allowed accurate perception of the location and extent of each ventilation/perfusion defect on the underlying CT anatomy, and characterised the pathophysiology of the various diseases. By reducing respiratory motion effects and enhancing perfusion/ventilation defect clarity, gated SPET can provide reliable co-registered images with CT images to accurately characterise regional functional impairment in various lung diseases.

Maturation of Sensori-Motor Functional Responses in the Preterm Brain.

PubMed

Allievi, Alessandro G; Arichi, Tomoki; Tusor, Nora; Kimpton, Jessica; Arulkumaran, Sophie; Counsell, Serena J; Edwards, A David; Burdet, Etienne

2016-01-01

Preterm birth engenders an increased risk of conditions like cerebral palsy and therefore this time may be crucial for the brain's developing sensori-motor system. However, little is known about how cortical sensori-motor function matures at this time, whether development is influenced by experience, and about its role in spontaneous motor behavior. We aimed to systematically characterize spatial and temporal maturation of sensori-motor functional brain activity across this period using functional MRI and a custom-made robotic stimulation device. We studied 57 infants aged from 30 + 2 to 43 + 2 weeks postmenstrual age. Following both induced and spontaneous right wrist movements, we saw consistent positive blood oxygen level-dependent functional responses in the contralateral (left) primary somatosensory and motor cortices. In addition, we saw a maturational trend toward faster, higher amplitude, and more spatially dispersed functional responses; and increasing integration of the ipsilateral hemisphere and sensori-motor associative areas. We also found that interhemispheric functional connectivity was significantly related to ex-utero exposure, suggesting the influence of experience-dependent mechanisms. At term equivalent age, we saw a decrease in both response amplitude and interhemispheric functional connectivity, and an increase in spatial specificity, culminating in the establishment of a sensori-motor functional response similar to that seen in adults. © The Author 2015. Published by Oxford University Press.

Beyond the Sensorimotor Plasticity: Cognitive Expansion of Prism Adaptation in Healthy Individuals.

PubMed

Michel, Carine

2015-01-01

Sensorimotor plasticity allows us to maintain an efficient motor behavior in reaction to environmental changes. One of the classical models for the study of sensorimotor plasticity is prism adaptation. It consists of pointing to visual targets while wearing prismatic lenses that shift the visual field laterally. The conditions of the development of the plasticity and the sensorimotor after-effects have been extensively studied for more than a century. However, the interest taken in this phenomenon was considerably increased since the demonstration of neglect rehabilitation following prism adaptation by Rossetti et al. (1998). Mirror effects, i.e., simulation of neglect in healthy individuals, were observed for the first time by Colent et al. (2000). The present review focuses on the expansion of prism adaptation to cognitive functions in healthy individuals during the last 15 years. Cognitive after-effects have been shown in numerous tasks even in those that are not intrinsically spatial in nature. Altogether, these results suggest the existence of a strong link between low-level sensorimotor plasticity and high-level cognitive functions and raise important questions about the mechanisms involved in producing unexpected cognitive effects following prism adaptation. Implications for the functional mechanisms and neuroanatomical network of prism adaptation are discussed to explain how sensorimotor plasticity may affect cognitive processes.

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

PubMed

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

2011-12-01

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

Beyond the Sensorimotor Plasticity: Cognitive Expansion of Prism Adaptation in Healthy Individuals

PubMed Central

Michel, Carine

2016-01-01

Sensorimotor plasticity allows us to maintain an efficient motor behavior in reaction to environmental changes. One of the classical models for the study of sensorimotor plasticity is prism adaptation. It consists of pointing to visual targets while wearing prismatic lenses that shift the visual field laterally. The conditions of the development of the plasticity and the sensorimotor after-effects have been extensively studied for more than a century. However, the interest taken in this phenomenon was considerably increased since the demonstration of neglect rehabilitation following prism adaptation by Rossetti et al. (1998). Mirror effects, i.e., simulation of neglect in healthy individuals, were observed for the first time by Colent et al. (2000). The present review focuses on the expansion of prism adaptation to cognitive functions in healthy individuals during the last 15 years. Cognitive after-effects have been shown in numerous tasks even in those that are not intrinsically spatial in nature. Altogether, these results suggest the existence of a strong link between low-level sensorimotor plasticity and high-level cognitive functions and raise important questions about the mechanisms involved in producing unexpected cognitive effects following prism adaptation. Implications for the functional mechanisms and neuroanatomical network of prism adaptation are discussed to explain how sensorimotor plasticity may affect cognitive processes. PMID:26779088

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

PubMed Central

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

2017-01-01

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

Alterations in post-movement beta event related synchronization throughout the migraine cycle: A controlled, longitudinal study.

PubMed

Mykland, Martin Syvertsen; Bjørk, Marte Helene; Stjern, Marit; Sand, Trond

2018-04-01

Background The migraine brain is believed to have altered cortical excitability compared to controls and between migraine cycle phases. Our aim was to evaluate post-activation excitability through post-movement beta event related synchronization (PMBS) in sensorimotor cortices with and without sensory discrimination. Subjects and methods We recorded EEG of 41 migraine patients and 31 healthy controls on three different days with classification of days in relation to migraine phases. During each recording, subjects performed one motor and one sensorimotor task with the right wrist. Controls and migraine patients in the interictal phase were compared with repeated measures (R-) ANOVA and two sample Student's t-test. Migraine phases were compared to the interictal phase with R-ANOVA and paired Student's t-test. Results The difference between PMBS at the contralateral and ipsilateral sensorimotor cortex was altered throughout the migraine cycle. Compared to the interictal phase, we found decreased PMBS at the ipsilateral sensorimotor cortex in the ictal phase and increased PMBS in the preictal phase. Lower ictal PMBS was found in bilateral sensorimotor cortices in patients with right side headache predominance. Conclusion The cyclic changes of PMBS in migraine patients may indicate that a dysfunction in deactivation and interhemispheric inhibition of the sensorimotor cortex is involved in the migraine attack cascade.

Distinct spatio-temporal profiles of beta-oscillations within visual and sensorimotor areas during action recognition as revealed by MEG.

PubMed

Pavlidou, Anastasia; Schnitzler, Alfons; Lange, Joachim

2014-05-01

The neural correlates of action recognition have been widely studied in visual and sensorimotor areas of the human brain. However, the role of neuronal oscillations involved during the process of action recognition remains unclear. Here, we were interested in how the plausibility of an action modulates neuronal oscillations in visual and sensorimotor areas. Subjects viewed point-light displays (PLDs) of biomechanically plausible and implausible versions of the same actions. Using magnetoencephalography (MEG), we examined dynamic changes of oscillatory activity during these action recognition processes. While both actions elicited oscillatory activity in visual and sensorimotor areas in several frequency bands, a significant difference was confined to the beta-band (∼20 Hz). An increase of power for plausible actions was observed in left temporal, parieto-occipital and sensorimotor areas of the brain, in the beta-band in successive order between 1650 and 2650 msec. These distinct spatio-temporal beta-band profiles suggest that the action recognition process is modulated by the degree of biomechanical plausibility of the action, and that spectral power in the beta-band may provide a functional interaction between visual and sensorimotor areas in humans. Copyright © 2014 Elsevier Ltd. All rights reserved.

Advantages of comparative studies in songbirds to understand the neural basis of sensorimotor integration.

PubMed

Murphy, Karagh; James, Logan S; Sakata, Jon T; Prather, Jonathan F

2017-08-01

Sensorimotor integration is the process through which the nervous system creates a link between motor commands and associated sensory feedback. This process allows for the acquisition and refinement of many behaviors, including learned communication behaviors such as speech and birdsong. Consequently, it is important to understand fundamental mechanisms of sensorimotor integration, and comparative analyses of this process can provide vital insight. Songbirds offer a powerful comparative model system to study how the nervous system links motor and sensory information for learning and control. This is because the acquisition, maintenance, and control of birdsong critically depend on sensory feedback. Furthermore, there is an incredible diversity of song organizations across songbird species, ranging from songs with simple, stereotyped sequences to songs with complex sequencing of vocal gestures, as well as a wide diversity of song repertoire sizes. Despite this diversity, the neural circuitry for song learning, control, and maintenance remains highly similar across species. Here, we highlight the utility of songbirds for the analysis of sensorimotor integration and the insights about mechanisms of sensorimotor integration gained by comparing different songbird species. Key conclusions from this comparative analysis are that variation in song sequence complexity seems to covary with the strength of feedback signals in sensorimotor circuits and that sensorimotor circuits contain distinct representations of elements in the vocal repertoire, possibly enabling evolutionary variation in repertoire sizes. We conclude our review by highlighting important areas of research that could benefit from increased comparative focus, with particular emphasis on the integration of new technologies. Copyright © 2017 the American Physiological Society.

Sensorimotor strategies for recognizing geometrical shapes: a comparative study with different sensory substitution devices

PubMed Central

Bermejo, Fernando; Di Paolo, Ezequiel A.; Hüg, Mercedes X.; Arias, Claudia

2015-01-01

The sensorimotor approach proposes that perception is constituted by the mastery of lawful sensorimotor regularities or sensorimotor contingencies (SMCs), which depend on specific bodily characteristics and on actions possibilities that the environment enables and constrains. Sensory substitution devices (SSDs) provide the user information about the world typically corresponding to one sensory modality through the stimulation of another modality. We investigate how perception emerges in novice adult participants equipped with vision-to-auditory SSDs while solving a simple geometrical shape recognition task. In particular, we examine the distinction between apparatus-related SMCs (those originating mostly in properties of the perceptual system) and object-related SMCs (those mostly connected with the perceptual task). We study the sensorimotor strategies employed by participants in three experiments with three different SSDs: a minimalist head-mounted SSD, a traditional, also head-mounted SSD (the vOICe) and an enhanced, hand-held echolocation device. Motor activity and fist-person data are registered and analyzed. Results show that participants are able to quickly learn the necessary skills to distinguish geometric shapes. Comparing the sensorimotor strategies utilized with each SSD we identify differential features of the sensorimotor patterns attributable mostly to the device, which account for the emergence of apparatus-based SMCs. These relate to differences in sweeping strategies between SSDs. We identify, also, components related to the emergence of object-related SMCs. These relate mostly to exploratory movements around the border of a shape. The study provides empirical support for SMC theory and discusses considerations about the nature of perception in sensory substitution. PMID:26106340

Dosimetric evaluation of the interplay effect in respiratory-gated RapidArc radiation therapy.

PubMed

Riley, Craig; Yang, Yong; Li, Tianfang; Zhang, Yongqian; Heron, Dwight E; Huq, M Saiful

2014-01-01

Volumetric modulated arc therapy (VMAT) with gating capability has had increasing adoption in many clinics in the United States. In this new technique, dose rate, gantry rotation speed, and the leaf motion speed of multileaf collimators (MLCs) are modulated dynamically during gated beam delivery to achieve highly conformal dose coverage of the target and normal tissue sparing. Compared with the traditional gated intensity-modulated radiation therapy technique, this complicated beam delivery technique may result in larger dose errors due to the intrafraction tumor motion. The purpose of this work is to evaluate the dosimetric influence of the interplay effect for the respiration-gated VMAT technique (RapidArc, Varian Medical Systems, Palo Alto, CA). Our work consisted of two parts: (1) Investigate the interplay effect for different target residual errors during gated RapidArc delivery using a one-dimensional moving phantom capable of producing stable sinusoidal movement; (2) Evaluate the dosimetric influence in ten clinical patients' treatment plans using a moving phantom driven with a patient-specific respiratory curve. For the first part of this study, four plans were created with a spherical target for varying residual motion of 0.25, 0.5, 0.75, and 1.0 cm. Appropriate gating windows were applied for each. The dosimetric effect was evaluated using EDR2 film by comparing the gated delivery with static delivery. For the second part of the project, ten gated lung stereotactic body radiotherapy cases were selected and reoptimized to be delivered by the gated RapidArc technique. These plans were delivered to a phantom, and again the gated treatments were compared to static deliveries by the same methods. For regular sinusoidal motion, the dose delivered to the target was not substantially affected by the gating windows when evaluated with the gamma statistics, suggesting the interplay effect has a small role in respiratory-gated RapidArc therapy. Varied results were seen when gated therapy was performed on the patient plans that could only be attributed to differences in patient respiratory patterns. Patients whose plans had the largest percentage of pixels failing the gamma statistics exhibited irregular breathing patterns including substantial interpatient variation in depth of respiration. The interplay effect has a limited impact on gated RapidArc therapy when evaluated with a linear phantom. Variations in patient breathing patterns, however, are of much greater clinical significance. Caution must be taken when evaluating patients' respiratory efforts for gated arc therapy.

Sensory Metrics of Neuromechanical Trust.

PubMed

Softky, William; Benford, Criscillia

2017-09-01

Today digital sources supply a historically unprecedented component of human sensorimotor data, the consumption of which is correlated with poorly understood maladies such as Internet addiction disorder and Internet gaming disorder. Because both natural and digital sensorimotor data share common mathematical descriptions, one can quantify our informational sensorimotor needs using the signal processing metrics of entropy, noise, dimensionality, continuity, latency, and bandwidth. Such metrics describe in neutral terms the informational diet human brains require to self-calibrate, allowing individuals to maintain trusting relationships. With these metrics, we define the trust humans experience using the mathematical language of computational models, that is, as a primitive statistical algorithm processing finely grained sensorimotor data from neuromechanical interaction. This definition of neuromechanical trust implies that artificial sensorimotor inputs and interactions that attract low-level attention through frequent discontinuities and enhanced coherence will decalibrate a brain's representation of its world over the long term by violating the implicit statistical contract for which self-calibration evolved. Our hypersimplified mathematical understanding of human sensorimotor processing as multiscale, continuous-time vibratory interaction allows equally broad-brush descriptions of failure modes and solutions. For example, we model addiction in general as the result of homeostatic regulation gone awry in novel environments (sign reversal) and digital dependency as a sub-case in which the decalibration caused by digital sensorimotor data spurs yet more consumption of them. We predict that institutions can use these sensorimotor metrics to quantify media richness to improve employee well-being; that dyads and family-size groups will bond and heal best through low-latency, high-resolution multisensory interaction such as shared meals and reciprocated touch; and that individuals can improve sensory and sociosensory resolution through deliberate sensory reintegration practices. We conclude that we humans are the victims of our own success, our hands so skilled they fill the world with captivating things, our eyes so innocent they follow eagerly.

Zic2 hypomorphic mutant mice as a schizophrenia model and ZIC2 mutations identified in schizophrenia patients

PubMed Central

Hatayama, Minoru; Ishiguro, Akira; Iwayama, Yoshimi; Takashima, Noriko; Sakoori, Kazuto; Toyota, Tomoko; Nozaki, Yayoi; Odaka, Yuri S.; Yamada, Kazuyuki; Yoshikawa, Takeo; Aruga, Jun

2011-01-01

ZIC2 is a causal gene for holoprosencephaly and encodes a zinc-finger-type transcriptional regulator. We characterized Zic2kd/+ mice with a moderate (40%) reduction in Zic2 expression. Zic2kd/+ mice showed increased locomotor activity in novel environments, cognitive and sensorimotor gating dysfunctions, and social behavioral abnormalities. Zic2kd/+ brain involved enlargement of the lateral ventricle, thinning of the cerebral cortex and corpus callosum, and decreased number of cholinergic neurons in the basal forebrain. Because these features are reminiscent of schizophrenia, we examined ZIC2 variant-carrying allele frequencies in schizophrenia patients and in controls in the Japanese population. Among three novel missense mutations in ZIC2, R409P was only found in schizophrenia patients, and was located in a strongly conserved position of the zinc finger domain. Mouse Zic2 with the corresponding mutation showed lowered transcription-activating capacity and had impaired target DNA-binding and co-factor-binding capacities. These results warrant further study of ZIC2 in the pathogenesis of schizophrenia. PMID:22355535

Early neuromodulation prevents the development of brain and behavioral abnormalities in a rodent model of schizophrenia.

PubMed

Hadar, R; Bikovski, L; Soto-Montenegro, M L; Schimke, J; Maier, P; Ewing, S; Voget, M; Wieske, F; Götz, T; Desco, M; Hamani, C; Pascau, J; Weiner, I; Winter, C

2018-04-01

The notion that schizophrenia is a neurodevelopmental disorder in which neuropathologies evolve gradually over the developmental course indicates a potential therapeutic window during which pathophysiological processes may be modified to halt disease progression or reduce its severity. Here we used a neurodevelopmental maternal immune stimulation (MIS) rat model of schizophrenia to test whether early targeted modulatory intervention would affect schizophrenia's neurodevelopmental course. We applied deep brain stimulation (DBS) or sham stimulation to the medial prefrontal cortex (mPFC) of adolescent MIS rats and respective controls, and investigated its behavioral, biochemical, brain-structural and -metabolic effects in adulthood. We found that mPFC-DBS successfully prevented the emergence of deficits in sensorimotor gating, attentional selectivity and executive function in adulthood, as well as the enlargement of lateral ventricle volumes and mal-development of dopaminergic and serotonergic transmission. These data suggest that the mPFC may be a valuable target for effective preventive treatments. This may have significant translational value, suggesting that targeting the mPFC before the onset of psychosis via less invasive neuromodulation approaches may be a viable preventive strategy.

Fmr1 and Nlgn3 knockout rats: novel tools for investigating autism spectrum disorders.

PubMed

Hamilton, Shannon M; Green, Jennie R; Veeraragavan, Surabi; Yuva, Lisa; McCoy, Aaron; Wu, Yumei; Warren, Joe; Little, Lara; Ji, Diana; Cui, Xiaoxia; Weinstein, Edward; Paylor, Richard

2014-04-01

Animal models are critical for gaining insights into autism spectrum disorder (ASD). Despite their apparent advantages to mice for neural studies, rats have not been widely used for disorders of the human CNS, such as ASD, for the lack of convenient genome manipulation tools. Here we describe two of the first transgenic rat models for ASD, developed using zinc-finger nuclease (ZFN) methodologies, and their initial behavioral assessment using a rapid juvenile test battery. A syndromic and nonsyndromic rat model for ASD were created as two separate knockout rat lines with heritable disruptions in the genes encoding Fragile X mental retardation protein (FMRP) and Neuroligin3 (NLGN3). FMRP, a protein with numerous proposed functions including regulation of mRNA and synaptic protein synthesis, and NLGN3, a member of the neuroligin synaptic cell-adhesion protein family, have been implicated in human ASD. Juvenile subjects from both knockout rat lines exhibited abnormalities in ASD-relevant phenotypes including juvenile play, perseverative behaviors, and sensorimotor gating. These data provide important first evidence regarding the utility of rats as genetic models for investigating ASD-relevant genes.

Modeling Autistic Features in Animals

PubMed Central

Patterson, Paul H.

2011-01-01

A variety of features of autism can be simulated in rodents, including the core behavioral hallmarks of stereotyped and repetitive behaviors, and deficits in social interaction and communication. Other behaviors frequently found in autism spectrum disorders (ASD) such as neophobia, enhanced anxiety, abnormal pain sensitivity and eye blink conditioning, disturbed sleep patterns, seizures, and deficits in sensorimotor gating are also present in some of the animal models. Neuropathology and some characteristic neurochemical changes that are frequently seen in autism, as well as alterations in the immune status in the brain and periphery are also found in some of the models. Several known environmental risk factors for autism have been successfully established in rodents, including maternal infection and maternal valproate administration. Also under investigation are a number of mouse models based on genetic variants associated with autism or on syndromic disorders with autistic features. This review briefly summarizes recent developments in this field, highlighting models with face and/or construct validity, and noting the potential for investigation of pathogenesis and early progress towards clinical testing of potential therapeutics. Wherever possible, reference is made to reviews rather than primary articles. PMID:21289542

An Aversive Response to Osmotic Upshift in Caenorhabditis elegans.

PubMed

Yu, Jingyi; Yang, Wenxing; Liu, He; Hao, Yingsong; Zhang, Yun

2017-01-01

Environmental osmolarity presents a common type of sensory stimulus to animals. While behavioral responses to osmotic changes are important for maintaining a stable intracellular osmolarity, the underlying mechanisms are not fully understood. In the natural habitat of Caenorhabditis elegans , changes in environmental osmolarity are commonplace. It is known that the nematode acutely avoids shocks of extremely high osmolarity. Here, we show that C. elegans also generates gradually increased aversion of mild upshifts in environmental osmolarity. Different from an acute avoidance of osmotic shocks that depends on the function of a transient receptor potential vanilloid channel, the slow aversion to osmotic upshifts requires the cGMP-gated sensory channel subunit TAX-2. TAX-2 acts in several sensory neurons that are exposed to body fluid to generate the aversive response through a motor network that underlies navigation. Osmotic upshifts activate the body cavity sensory neuron URX, which is known to induce aversion upon activation. Together, our results characterize the molecular and cellular mechanisms underlying a novel sensorimotor response to osmotic stimuli and reveal that C. elegans engages different behaviors and the underlying mechanisms to regulate responses to extracellular osmolarity.

Dysregulated expression of neuregulin-1 by cortical pyramidal neurons disrupts synaptic plasticity.

PubMed

Agarwal, Amit; Zhang, Mingyue; Trembak-Duff, Irina; Unterbarnscheidt, Tilmann; Radyushkin, Konstantin; Dibaj, Payam; Martins de Souza, Daniel; Boretius, Susann; Brzózka, Magdalena M; Steffens, Heinz; Berning, Sebastian; Teng, Zenghui; Gummert, Maike N; Tantra, Martesa; Guest, Peter C; Willig, Katrin I; Frahm, Jens; Hell, Stefan W; Bahn, Sabine; Rossner, Moritz J; Nave, Klaus-Armin; Ehrenreich, Hannelore; Zhang, Weiqi; Schwab, Markus H

2014-08-21

Neuregulin-1 (NRG1) gene variants are associated with increased genetic risk for schizophrenia. It is unclear whether risk haplotypes cause elevated or decreased expression of NRG1 in the brains of schizophrenia patients, given that both findings have been reported from autopsy studies. To study NRG1 functions in vivo, we generated mouse mutants with reduced and elevated NRG1 levels and analyzed the impact on cortical functions. Loss of NRG1 from cortical projection neurons resulted in increased inhibitory neurotransmission, reduced synaptic plasticity, and hypoactivity. Neuronal overexpression of cysteine-rich domain (CRD)-NRG1, the major brain isoform, caused unbalanced excitatory-inhibitory neurotransmission, reduced synaptic plasticity, abnormal spine growth, altered steady-state levels of synaptic plasticity-related proteins, and impaired sensorimotor gating. We conclude that an "optimal" level of NRG1 signaling balances excitatory and inhibitory neurotransmission in the cortex. Our data provide a potential pathomechanism for impaired synaptic plasticity and suggest that human NRG1 risk haplotypes exert a gain-of-function effect. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

p53 activated by AND gate genetic circuit under radiation and hypoxia for targeted cancer gene therapy

PubMed Central

Ding, Miao; Li, Rong; He, Rong; Wang, Xingyong; Yi, Qijian; Wang, Weidong

2015-01-01

Radio-activated gene therapy has been developed as a novel therapeutic strategy against cancer; however, expression of therapeutic gene in peritumoral tissues will result in unacceptable toxicity to normal cells. To restrict gene expression in targeted tumor mass, we used hypoxia and radiation tolerance features of tumor cells to develop a synthetic AND gate genetic circuit through connecting radiation sensitivity promoter cArG6, heat shock response elements SNF1, HSF1 and HSE4 with retroviral vector plxsn. Their construction and dynamic activity process were identified through downstream enhanced green fluorescent protein and wtp53 expression in non-small cell lung cancer A549 cells and in a nude mice model. The result showed that AND gate genetic circuit could be activated by lower required radiation dose (6 Gy) and after activated, AND gate could induce significant apoptosis effects and growth inhibition of cancer cells in vitro and in vivo. The radiation- and hypoxia-activated AND gate genetic circuit, which could lead to more powerful target tumoricidal activity represented a promising strategy for both targeted and effective gene therapy of human lung adenocarcinoma and low dose activation character of the AND gate genetic circuit implied that this model could be further exploited to decrease side-effects of clinical radiation therapy. PMID:26177264

Eye tracking and gating system for proton therapy of orbital tumors

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

Shin, Dongho; Yoo, Seung Hoon; Moon, Sung Ho

2012-07-15

Purpose: A new motion-based gated proton therapy for the treatment of orbital tumors using real-time eye-tracking system was designed and evaluated. Methods: We developed our system by image-pattern matching, using a normalized cross-correlation technique with LabVIEW 8.6 and Vision Assistant 8.6 (National Instruments, Austin, TX). To measure the pixel spacing of an image consistently, four different calibration modes such as the point-detection, the edge-detection, the line-measurement, and the manual measurement mode were suggested and used. After these methods were applied to proton therapy, gating was performed, and radiation dose distributions were evaluated. Results: Moving phantom verification measurements resulted in errorsmore » of less than 0.1 mm for given ranges of translation. Dosimetric evaluation of the beam-gating system versus nongated treatment delivery with a moving phantom shows that while there was only 0.83 mm growth in lateral penumbra for gated radiotherapy, there was 4.95 mm growth in lateral penumbra in case of nongated exposure. The analysis from clinical results suggests that the average of eye movements depends distinctively on each patient by showing 0.44 mm, 0.45 mm, and 0.86 mm for three patients, respectively. Conclusions: The developed automatic eye-tracking based beam-gating system enabled us to perform high-precision proton radiotherapy of orbital tumors.« less

Graphene field effect transistor without an energy gap.

PubMed

Jang, Min Seok; Kim, Hyungjun; Son, Young-Woo; Atwater, Harry A; Goddard, William A

2013-05-28

Graphene is a room temperature ballistic electron conductor and also a very good thermal conductor. Thus, it has been regarded as an ideal material for postsilicon electronic applications. A major complication is that the relativistic massless electrons in pristine graphene exhibit unimpeded Klein tunneling penetration through gate potential barriers. Thus, previous efforts to realize a field effect transistor for logic applications have assumed that introduction of a band gap in graphene is a prerequisite. Unfortunately, extrinsic treatments designed to open a band gap seriously degrade device quality, yielding very low mobility and uncontrolled on/off current ratios. To solve this dilemma, we propose a gating mechanism that leads to a hundredfold enhancement in on/off transmittance ratio for normally incident electrons without any band gap engineering. Thus, our saw-shaped geometry gate potential (in place of the conventional bar-shaped geometry) leads to switching to an off state while retaining the ultrahigh electron mobility in the on state. In particular, we report that an on/off transmittance ratio of 130 is achievable for a sawtooth gate with a gate length of 80 nm. Our switching mechanism demonstrates that intrinsic graphene can be used in designing logic devices without serious alteration of the conventional field effect transistor architecture. This suggests a new variable for the optimization of the graphene-based device--geometry of the gate electrode.

Normally-off p-GaN/AlGaN/GaN high electron mobility transistors using hydrogen plasma treatment

NASA Astrophysics Data System (ADS)

Hao, Ronghui; Fu, Kai; Yu, Guohao; Li, Weiyi; Yuan, Jie; Song, Liang; Zhang, Zhili; Sun, Shichuang; Li, Xiajun; Cai, Yong; Zhang, Xinping; Zhang, Baoshun

2016-10-01

In this letter, we report a method by introducing hydrogen plasma treatment to realize normally-off p-GaN/AlGaN/GaN HEMT devices. Instead of using etching technology, hydrogen plasma was adopted to compensate holes in the p-GaN above the two dimensional electron gas (2DEG) channel to release electrons in the 2DEG channel and form high-resistivity area to reduce leakage current and increase gate control capability. The fabricated p-GaN/AlGaN/GaN HEMT exhibits normally-off operation with a threshold voltage of 1.75 V, a subthreshold swing of 90 mV/dec, a maximum transconductance of 73.1 mS/mm, an ON/OFF ratio of 1 × 107, a breakdown voltage of 393 V, and a maximum drain current density of 188 mA/mm at a gate bias of 6 V. The comparison of the two processes of hydrogen plasma treatment and p-GaN etching has also been made in this work.

Intramuscular Neurotrophin-3 normalizes low threshold spinal reflexes, reduces spasms and improves mobility after bilateral corticospinal tract injury in rats

PubMed Central

Kathe, Claudia; Hutson, Thomas Haynes; McMahon, Stephen Brendan; Moon, Lawrence David Falcon

2016-01-01

Brain and spinal injury reduce mobility and often impair sensorimotor processing in the spinal cord leading to spasticity. Here, we establish that complete transection of corticospinal pathways in the pyramids impairs locomotion and leads to increased spasms and excessive mono- and polysynaptic low threshold spinal reflexes in rats. Treatment of affected forelimb muscles with an adeno-associated viral vector (AAV) encoding human Neurotrophin-3 at a clinically-feasible time-point after injury reduced spasticity. Neurotrophin-3 normalized the short latency Hoffmann reflex to a treated hand muscle as well as low threshold polysynaptic spinal reflexes involving afferents from other treated muscles. Neurotrophin-3 also enhanced locomotor recovery. Furthermore, the balance of inhibitory and excitatory boutons in the spinal cord and the level of an ion co-transporter in motor neuron membranes required for normal reflexes were normalized. Our findings pave the way for Neurotrophin-3 as a therapy that treats the underlying causes of spasticity and not only its symptoms. DOI: http://dx.doi.org/10.7554/eLife.18146.001 PMID:27759565

Dancing Effects on Preschoolers' Sensorimotor Synchronization, Balance, and Movement Reaction Time.

PubMed

Chatzihidiroglou, Panagiota; Chatzopoulos, Dimitris; Lykesas, Georgios; Doganis, Georgios

2018-06-01

In the present study, we compared an experimental group of preschool children ( n = 22; mean age = 5 years, 8 months) who followed an 8-week dance program with a control group ( n = 20; mean age = 5 years, 5 months) on pre-post measures of sensorimotor synchronization (K-Rhythm Test), balancing on one leg and movement reaction time. Compared with the control participants, the dance group demonstrated significantly better pretest to posttest improvements on sensorimotor synchronization and balance (but not movement reaction time). Considering the importance of sensorimotor synchronization and balance for subsequent child development and performance of daily and sport activities, these results suggest that dancing should be included in early childhood curricula.

The efficacy of a HUBER exercise system mediated sensorimotor training protocol on proprioceptive system, lumbar movement control and quality of life in patients with chronic non-specific low back pain.

PubMed

Letafatkar, Amir; Nazarzadeh, Maryam; Hadadnezhad, Malihe; Farivar, Niloufar

2017-08-03

There is a relation between deficits of the proprioceptive system and movement control dysfunction in patients with chronic low back pain (LBP) but, the exact mechanism of this relation is unknown. Exercise therapy has been recognized as an effective method for low back pain treatment. In spite of this, it is not clear which of the various exercise therapy programs lead to better results. Therefore, the present analyze the efficacy of a HUBER study aims to exercise system mediated sensorimotor training protocol on proprioceptive system, lumbar movement control (LMC) and quality of life (QOL) in patients with chronic non-specific LBP. Quasi-experimental study. 53 patients with chronic non-specific LBP (mean age 37.55 ± 6.67 years,and Body Mass Index (BMI) 22.4 ± 3.33) were selected by using Roland-Morris Disability Questionnaire (RMQ) and were assigned into two experimental (N= 27) and control groups (N= 26) The experimental group underwent a five-week (10 sessions) Sensorimotor training by using the Human Body Equalizer (HUBER) spine force under the supervision of an investigator. The movement control battery tests, the HUBER machine testing option, goniometer and visual analogue scale used for movement control, neuromuscular coordination, proprioception and LBP assessment respectively. The assessments were completed in pre-test and after five weeks. The paired and sample T tests were used for data analysis in SPSS program version 18 (Significance level were set at a P value < 0.05). The HUBER system mediated sensorimotor training demonstrated significant improvement in the proprioceptive system, LMC and QOL (P= 0.001). Also There was a significant reduction in the pain scores of subjects with chronic non-specific LBP in the sensorimotor group (P= 0.001). In this study, only the short term effects of the sensorimotor training were examined. The results suggest that a sensorimotor training program causes significant improvement in patients with chronic non-specific LBP. Future research should be carried out with a larger sample size to examine the long term effects of the sensorimotor training program on treatment of patients with chronic non-specific LBP. Considering the efficacy of the sensorimotor training, it is recommended that this intervention should be applied to treatment of patients with chronic non-specific LBP in the future.

A study on quantitative analysis of field size and dose by using gating system in 4D conformal radiation treatment

NASA Astrophysics Data System (ADS)

Ji, Youn-Sang; Dong, Kyung-Rae; Kim, Chang-Bok; Chung, Woon-Kwan; Cho, Jae-Hwan; Lee, Hae-Kag

2012-10-01

This study evaluated the gating-based 4-D conformal radiation therapy (4D-CT) treatment planning by a comparison with the common 3-D conformal radiation therapy (3D-CT) treatment planning and examined the change in treatment field size and dose to the tumors and adjacent normal tissues because an unnecessary dose is also included in the 3-D treatment planning for the radiation treatment of tumors in the chest and abdomen. The 3D-CT and gating-based 4D-CT images were obtained from patients who had undergone radiation treatment for chest and abdomen tumors in the oncology department. After establishing a treatment plan, the CT treatment and planning system were used to measure the change in field size for analysis. A dose volume histogram (DVH) was used to calculate the appropriate dose to planning target volume (PTV) tumors and adjacent normal tissue. The difference in the treatment volume of the chest was 0.6 and 0.83 cm on the X- and Y-axis, respectively, for the gross tumor volume (GTV). Accordingly, the values in the 4D-CT treatment planning were smaller and the dose was more concentrated by 2.7% and 0.9% on the GTV and clinical target volume (CTV), respectively. The normal tissues in the surrounding normal tissues were reduced by 3.0%, 7.2%, 0.4%, 1.7%, 2.6% and 0.2% in the bronchus, chest wall, esophagus, heart, lung and spinal cord, respectively. The difference in the treatment volume of the abdomen was 0.72 cm on the X-axis and 0.51 cm on the Y-axis for the GTV; and 1.06 cm on the X-axis and 1.85 cm on the Y-axis for the PTV. Therefore, the values in the 4D-CT treatment planning were smaller. The dose was concentrated by 6.8% and 4.3% on the GTV and PTV, respectively, whereas the adjacent normal tissues in the cord, Lt. kidney, Rt. kidney, small bowels and whole liver were reduced by 3.2%, 4.2%, 1.5%, 6.2% and 12.7%, respectively. The treatment field size was smaller in volume in the case of the 4D-CT treatment planning. In the DVH, the 4D-CT treatment planning showed a higher dose concentration on the part to be treated than the 3D-CT treatment planning with a lower dose to the adjacent normal tissues. Overall, the gating-based 4D-CT treatment planning is believed to be more helpful than the 3D-CT treatment planning.

Genotyping of single nucleotide polymorphism by probe-gated silica nanoparticles.

PubMed

Ercan, Meltem; Ozalp, Veli C; Tuna, Bilge G

2017-11-15

The development of simple, reliable, and rapid approaches for molecular detection of common mutations is important for prevention and early diagnosis of genetic diseases, including Thalessemia. Oligonucleotide-gated mesoporous nanoparticles-based analysis is a new platform for mutation detection that has the advantages of sensitivity, rapidity, accuracy, and convenience. A specific mutation in β-thalassemia, one of the most prevalent inherited diseases in several countries, was used as model disease in this study. An assay for detection of IVS110 point mutation (A > G reversion) was developed by designing probe-gated mesoporous silica nanoparticles (MCM-41) loaded with reporter fluorescein molecules. The silica nanoparticles were characterized by AFM, TEM and BET analysis for having 180 nm diameter and 2.83 nm pore size regular hexagonal shape. Amine group functionalized nanoparticles were analysed with FTIR technique. Mutated and normal sequence probe oligonucleotides)about 12.7 nmol per mg nanoparticles) were used to entrap reporter fluorescein molecules inside the pores and hybridization with single stranded DNA targets amplified by PCR gave different fluorescent signals for mutated targets. Samples from IVS110 mutated and normal patients resulted in statistically significant differences when the assay procedure were applied. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of the dielectric for the charging dynamics of the dielectric/barrier interface in AlGaN/GaN based metal-insulator-semiconductor structures under forward gate bias stress

NASA Astrophysics Data System (ADS)

Lagger, P.; Steinschifter, P.; Reiner, M.; Stadtmüller, M.; Denifl, G.; Naumann, A.; Müller, J.; Wilde, L.; Sundqvist, J.; Pogany, D.; Ostermaier, C.

2014-07-01

The high density of defect states at the dielectric/III-N interface in GaN based metal-insulator-semiconductor structures causes tremendous threshold voltage drifts, ΔVth, under forward gate bias conditions. A comprehensive study on different dielectric materials, as well as varying dielectric thickness tD and barrier thickness tB, is performed using capacitance-voltage analysis. It is revealed that the density of trapped electrons, ΔNit, scales with the dielectric capacitance under spill-over conditions, i.e., the accumulation of a second electron channel at the dielectric/AlGaN barrier interface. Hence, the density of trapped electrons is defined by the charging of the dielectric capacitance. The scaling behavior of ΔNit is explained universally by the density of accumulated electrons at the dielectric/III-N interface under spill-over conditions. We conclude that the overall density of interface defects is higher than what can be electrically measured, due to limits set by dielectric breakdown. These findings have a significant impact on the correct interpretation of threshold voltage drift data and are of relevance for the development of normally off and normally on III-N/GaN high electron mobility transistors with gate insulation.

Manual Tactile Test Predicts Sensorimotor Control Capability of Hands for Patients With Peripheral Nerve Injury.

PubMed

Hsu, Hsiu-Yun; Shieh, Shyh-Jou; Kuan, Ta-Shen; Yang, Hsiu-Ching; Su, Fong-Chin; Chiu, Haw-Yen; Kuo, Li-Chieh

2016-06-01

To comprehend the merits of a Manual Tactile Test (MTT) in assessing hand sensorimotor functions by exploring the relations among 3 subtests along with the precision pinch performances for patients with peripheral nerve injuries (PNIs); and to understand the accuracy of the MTT by constructing the sensitivity and specificity of the test for patients with PNI. Case-control study. Hospital and local community. Patients with PNI (n=28) were recruited along with age-, sex-, and handedness-matched healthy controls (n=28) (N=56). Not applicable. The Semmes-Weinstein monofilament, moving and static 2-point discrimination, roughness differentiation, stereognosis and barognosis subtests of the MTT, and precision pinch performance were used to examine the sensory and sensorimotor status of the hand. The worst results in all sensibility tests were found for the patients with PNI (P<.001) in comparison with the controls. Multiple linear regression analysis showed the MTT was a better indicator for predicting the sensorimotor capacity of hands in the patients with PNI (r(2)=.189, P=.003) than the traditional test (r(2)=.088, P=.051). The results of the receiver operating characteristic curve estimation show that the area under the curve was .968 and .959 for the roughness differentiation and stereognosis subtests, respectively, and .853 for the barognosis subtest, therefore revealing the accuracy of the MTT in assessing sensorimotor status for patients with PNI. This study indicates that the MTT is highly accurate and a significant predictor of sensorimotor performance in hands of patients with PNI. The MTT could therefore help clinicians obtain a better understanding of the sensorimotor and functional status of the hand with nerve injuries. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Validity of semi-quantitative scale for brain MRI in unilateral cerebral palsy due to periventricular white matter lesions: Relationship with hand sensorimotor function and structural connectivity.

PubMed

Fiori, Simona; Guzzetta, Andrea; Pannek, Kerstin; Ware, Robert S; Rossi, Giuseppe; Klingels, Katrijn; Feys, Hilde; Coulthard, Alan; Cioni, Giovanni; Rose, Stephen; Boyd, Roslyn N

2015-01-01

To provide first evidence of construct validity of a semi-quantitative scale for brain structural MRI (sqMRI scale) in children with unilateral cerebral palsy (UCP) secondary to periventricular white matter (PWM) lesions, by examining the relationship with hand sensorimotor function and whole brain structural connectivity. Cross-sectional study of 50 children with UCP due to PWM lesions using 3 T (MRI), diffusion MRI and assessment of hand sensorimotor function. We explored the relationship of lobar, hemispheric and global scores on the sqMRI scale, with fractional anisotropy (FA), as a measure of brain white matter microstructure, and with hand sensorimotor measures (Assisting Hand Assessment, AHA; Jebsen-Taylor Test for Hand Function, JTTHF; Melbourne Assessment of Unilateral Upper Limb Function, MUUL; stereognosis; 2-point discrimination). Lobar and hemispheric scores on the sqMRI scale contralateral to the clinical side of hemiplegia correlated with sensorimotor paretic hand function measures and FA of a number of brain structural connections, including connections of brain areas involved in motor control (postcentral, precentral and paracentral gyri in the parietal lobe). More severe lesions correlated with lower sensorimotor performance, with the posterior limb of internal capsule score being the strongest contributor to impaired hand function. The sqMRI scale demonstrates first evidence of construct validity against impaired motor and sensory function measures and brain structural connectivity in a cohort of children with UCP due to PWM lesions. More severe lesions correlated with poorer paretic hand sensorimotor function and impaired structural connectivity in the hemisphere contralateral to the clinical side of hemiplegia. The quantitative structural MRI scoring may be a useful clinical tool for studying brain structure-function relationships but requires further validation in other populations of CP.

Does the sensorimotor system minimize prediction error or select the most likely prediction during object lifting?

PubMed Central

McGregor, Heather R.; Pun, Henry C. H.; Buckingham, Gavin; Gribble, Paul L.

2016-01-01

The human sensorimotor system is routinely capable of making accurate predictions about an object's weight, which allows for energetically efficient lifts and prevents objects from being dropped. Often, however, poor predictions arise when the weight of an object can vary and sensory cues about object weight are sparse (e.g., picking up an opaque water bottle). The question arises, what strategies does the sensorimotor system use to make weight predictions when one is dealing with an object whose weight may vary? For example, does the sensorimotor system use a strategy that minimizes prediction error (minimal squared error) or one that selects the weight that is most likely to be correct (maximum a posteriori)? In this study we dissociated the predictions of these two strategies by having participants lift an object whose weight varied according to a skewed probability distribution. We found, using a small range of weight uncertainty, that four indexes of sensorimotor prediction (grip force rate, grip force, load force rate, and load force) were consistent with a feedforward strategy that minimizes the square of prediction errors. These findings match research in the visuomotor system, suggesting parallels in underlying processes. We interpret our findings within a Bayesian framework and discuss the potential benefits of using a minimal squared error strategy. NEW & NOTEWORTHY Using a novel experimental model of object lifting, we tested whether the sensorimotor system models the weight of objects by minimizing lifting errors or by selecting the statistically most likely weight. We found that the sensorimotor system minimizes the square of prediction errors for object lifting. This parallels the results of studies that investigated visually guided reaching, suggesting an overlap in the underlying mechanisms between tasks that involve different sensory systems. PMID:27760821

Comparison of Gated Audiovisual Speech Identification in Elderly Hearing Aid Users and Elderly Normal-Hearing Individuals: Effects of Adding Visual Cues to Auditory Speech Stimuli.

PubMed

Moradi, Shahram; Lidestam, Björn; Rönnberg, Jerker

2016-06-17

The present study compared elderly hearing aid (EHA) users (n = 20) with elderly normal-hearing (ENH) listeners (n = 20) in terms of isolation points (IPs, the shortest time required for correct identification of a speech stimulus) and accuracy of audiovisual gated speech stimuli (consonants, words, and final words in highly and less predictable sentences) presented in silence. In addition, we compared the IPs of audiovisual speech stimuli from the present study with auditory ones extracted from a previous study, to determine the impact of the addition of visual cues. Both participant groups achieved ceiling levels in terms of accuracy in the audiovisual identification of gated speech stimuli; however, the EHA group needed longer IPs for the audiovisual identification of consonants and words. The benefit of adding visual cues to auditory speech stimuli was more evident in the EHA group, as audiovisual presentation significantly shortened the IPs for consonants, words, and final words in less predictable sentences; in the ENH group, audiovisual presentation only shortened the IPs for consonants and words. In conclusion, although the audiovisual benefit was greater for EHA group, this group had inferior performance compared with the ENH group in terms of IPs when supportive semantic context was lacking. Consequently, EHA users needed the initial part of the audiovisual speech signal to be longer than did their counterparts with normal hearing to reach the same level of accuracy in the absence of a semantic context. © The Author(s) 2016.

Cervical sensorimotor control in idiopathic cervical dystonia: A cross-sectional study.

PubMed

De Pauw, Joke; Mercelis, Rudy; Hallemans, Ann; Michiels, Sarah; Truijen, Steven; Cras, Patrick; De Hertogh, Willem

2017-09-01

Patients with idiopathic adult-onset cervical dystonia (CD) experience an abnormal head posture and involuntary muscle contractions. Although the exact areas affected in the central nervous system remain uncertain, impaired functions in systems stabilizing the head and neck are apparent such as the somatosensory and sensorimotor integration systems. The aim of the study is to investigate cervical sensorimotor control dysfunction in patients with CD. Cervical sensorimotor control was assessed by a head repositioning task in 24 patients with CD and 70 asymptomatic controls. Blindfolded participants were asked to reposition their head to a previously memorized neutral head position (NHP) following an active movement (flexion, extension, left, and right rotation). The repositioning error (joint position error, JPE) was registered via 3D motion analysis with an eight-camera infrared system (VICON ® T10). Disease-specific characteristics of all patients were obtained via the Tsui scale, Cervical Dystonia Impact Profile (CDIP-58), and Toronto Western Spasmodic Rating Scale. Patients with CD showed larger JPE than controls (mean difference of 1.5°, p  <   .006), and systematically 'overshoot', i.e. surpassed the NHP, whereas control subjects 'undershoot', i.e. fall behind the NHP. The JPE did not correlate with disease-specific characteristics. Cervical sensorimotor control is impaired in patients with CD. As cervical sensorimotor control can be trained, this might be a potential treatment option for therapy, adjuvant to botulinum toxin injections.

Finger tapping and pre-attentive sensorimotor timing in adults with ADHD.

PubMed

Hove, Michael J; Gravel, Nickolas; Spencer, Rebecca M C; Valera, Eve M

2017-12-01

Sensorimotor timing deficits are considered central to attention-deficit/hyperactivity disorder (ADHD). However, the tasks establishing timing impairments often involve interconnected processes, including low-level sensorimotor timing and higher level executive processes such as attention. Thus, the source of timing deficits in ADHD remains unclear. Low-level sensorimotor timing can be isolated from higher level processes in a finger-tapping task that examines the motor response to unexpected shifts of metronome onsets. In this study, adults with ADHD and ADHD-like symptoms (n = 25) and controls (n = 26) performed two finger-tapping tasks. The first assessed tapping variability in a standard tapping task (metronome-paced and unpaced). In the other task, participants tapped along with a metronome that contained unexpected shifts (±15, 50 ms); the timing adjustment on the tap following the shift captures pre-attentive sensorimotor timing (i.e., phase correction) and thus should be free of potential higher order confounds (e.g., attention). In the standard tapping task, as expected, the ADHD group had higher timing variability in both paced and unpaced tappings. However, in the pre-attentive task, performance did not differ between the ADHD and control groups. Together, results suggest that low-level sensorimotor timing and phase correction are largely preserved in ADHD and that some timing impairments observed in ADHD may stem from higher level factors (such as sustained attention).

Multi-unit activity suppression and sensorimotor deficits after endothelin-1-induced middle cerebral artery occlusion in conscious rats.

PubMed

Moyanova, Slavianka; Kirov, Roumen; Kortenska, Lidia

2003-08-15

Conscious Wistar rats with stereotaxically and unilaterally implanted cannula just above the middle cerebral artery (MCA) were injected with the powerful vasoconstrictor peptide endothelin-1 (ET1, 60 pmol in 3 microl). The purpose was to examine the long-term (from the 1st to the 14th day) changes in neuronal bioelectrical activity together with sensorimotor deficits after ET1-induced MCA occlusion (MCAO). Extracellular multi-unit activity (MUA) recorded from the ipsilateral fronto-parietal cortical area (supplied by MCA) and sensorimotor behavior (one postural reflex test and six limb placing tests) were examined. A significant suppression of the multi-unit activity was observed until the 14th day post-ET1. The rats exhibited significant unilateral sensorimotor deficits with a maximum at the 3-7 days after ET1 and a spontaneous partial recovery by days 11-14. A significant correlation was found between the suppression of the multi-unit activity and the sensorimotor deficits between the 3rd and the 10th day post-ET1. The results suggest that studying the bioelectrical activity in combination with the behavioral sensorimotor functions may be of use to assess the functional disturbances associated with focal cerebral ischemia and would help to examine the therapeutic benefits of various cerebroprotective treatments before initiating human clinical trials.

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

PubMed

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

2015-11-01

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

Gap Junctional Coupling in Lenses from α8 Connexin Knockout Mice

PubMed Central

Baldo, George J.; Gong, Xiaohua; Martinez-Wittinghan, Francisco J.; Kumar, Nalin M.; Gilula, Norton B.; Mathias, Richard T.

2001-01-01

Lens fiber cell gap junctions contain α3 (Cx46) and α8 (Cx50) connexins. To examine the roles of the two different connexins in lens physiology, we have genetically engineered mice lacking either α3 or α8 connexin. Intracellular impedance studies of these lenses were used to measure junctional conductance and its sensitivity to intracellular pH. In Gong et al. 1998, we described results from α3 connexin knockout lenses. Here, we present original data from α8 connexin knockout lenses and a comparison with the previous results. The lens has two functionally distinct domains of fiber cell coupling. In wild-type mouse lenses, the outer shell of differentiating fibers (see 1, DF) has an average coupling conductance per area of cell–cell contact of ∼1 S/cm2, which falls to near zero when the cytoplasm is acidified. In the inner core of mature fibers (see 1, MF), the average coupling conductance is ∼0.4 S/cm2, and is insensitive to acidification of the cytoplasm. Both connexin isoforms appear to contribute about equally in the DF since the coupling conductance for either heterozygous knockout (+/−) was ∼70% of normal and 30–40% of the normal for both −/− lenses. However, their contribution to the MF was different. About 50% of the normal coupling conductance was found in the MF of α3 +/− lenses. In contrast, the coupling of MF in the α8 +/− lenses was the same as normal. Moreover, no coupling was detected in the MF of α3 −/− lenses. Together, these results suggest that α3 connexin alone is responsible for coupling MF. The pH- sensitive gating of DF junctions was about the same in wild-type and α3 connexin −/− lenses. However, in α8 −/− lenses, the pure α3 connexin junctions did not gate closed in the response to acidification. Since α3 connexin contributes about half the coupling conductance in DF of wild-type lenses, and that conductance goes to zero when the cytoplasmic pH drops, it appears α8 connexin regulates the gating of α3 connexin. Both connexins are clearly important to lens physiology as lenses null for either connexin lose transparency. Gap junctions in the MF survive for the lifetime of the organism without protein turnover. It appears that α3 connexin provides the long-term communication in MF. Gap junctions in DF may be physiologically regulated since they are capable of gating when the cytoplasm is acidified. It appears α8 connexin is required for gating in DF. PMID:11696604

A Forward Genetic Screen in Zebrafish Identifies the G-Protein-Coupled Receptor CaSR as a Modulator of Sensorimotor Decision Making.

PubMed

Jain, Roshan A; Wolman, Marc A; Marsden, Kurt C; Nelson, Jessica C; Shoenhard, Hannah; Echeverry, Fabio A; Szi, Christina; Bell, Hannah; Skinner, Julianne; Cobbs, Emilia N; Sawada, Keisuke; Zamora, Amy D; Pereda, Alberto E; Granato, Michael

2018-05-07

Animals continuously integrate sensory information and select contextually appropriate responses. Here, we show that zebrafish larvae select a behavioral response to acoustic stimuli from a pre-existing choice repertoire in a context-dependent manner. We demonstrate that this sensorimotor choice is modulated by stimulus quality and history, as well as by neuromodulatory systems-all hallmarks of more complex decision making. Moreover, from a genetic screen coupled with whole-genome sequencing, we identified eight mutants with deficits in this sensorimotor choice, including mutants of the vertebrate-specific G-protein-coupled extracellular calcium-sensing receptor (CaSR), whose function in the nervous system is not well understood. We demonstrate that CaSR promotes sensorimotor decision making acutely through Gα i/o and Gα q/11 signaling, modulated by clathrin-mediated endocytosis. Combined, our results identify the first set of genes critical for behavioral choice modulation in a vertebrate and reveal an unexpected critical role for CaSR in sensorimotor decision making. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

PubMed

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

2010-10-01

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

The Role of Sensorimotor Difficulties in Autism Spectrum Conditions

PubMed Central

Hannant, Penelope; Tavassoli, Teresa; Cassidy, Sarah

2016-01-01

In addition to difficulties in social communication, current diagnostic criteria for autism spectrum conditions (ASC) also incorporate sensorimotor difficulties, repetitive motor movements, and atypical reactivity to sensory input (1). This paper explores whether sensorimotor difficulties are associated with the development and maintenance of symptoms in ASC. First, studies have shown difficulties coordinating sensory input into planning and executing movement effectively in ASC. Second, studies have shown associations between sensory reactivity and motor coordination with core ASC symptoms, suggesting these areas each strongly influence the development of social and communication skills. Third, studies have begun to demonstrate that sensorimotor difficulties in ASC could account for reduced social attention early in development, with a cascading effect on later social, communicative and emotional development. These results suggest that sensorimotor difficulties not only contribute to non-social difficulties such as narrow circumscribed interests, but also to the development of social behaviors such as effectively coordinating eye contact with speech and gesture, interpreting others’ behavior, and responding appropriately. Further research is needed to explore the link between sensory and motor difficulties in ASC and their contribution to the development and maintenance of ASC. PMID:27559329

Taking Aim at the Cognitive Side of Learning in Sensorimotor Adaptation Tasks.

PubMed

McDougle, Samuel D; Ivry, Richard B; Taylor, Jordan A

2016-07-01

Sensorimotor adaptation tasks have been used to characterize processes responsible for calibrating the mapping between desired outcomes and motor commands. Research has focused on how this form of error-based learning takes place in an implicit and automatic manner. However, recent work has revealed the operation of multiple learning processes, even in this simple form of learning. This review focuses on the contribution of cognitive strategies and heuristics to sensorimotor learning, and how these processes enable humans to rapidly explore and evaluate novel solutions to enable flexible, goal-oriented behavior. This new work points to limitations in current computational models, and how these must be updated to describe the conjoint impact of multiple processes in sensorimotor learning. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Hebbian learning rule gives rise to mirror neurons and links them to control theoretic inverse models.

PubMed

Hanuschkin, A; Ganguli, S; Hahnloser, R H R

2013-01-01

Mirror neurons are neurons whose responses to the observation of a motor act resemble responses measured during production of that act. Computationally, mirror neurons have been viewed as evidence for the existence of internal inverse models. Such models, rooted within control theory, map-desired sensory targets onto the motor commands required to generate those targets. To jointly explore both the formation of mirrored responses and their functional contribution to inverse models, we develop a correlation-based theory of interactions between a sensory and a motor area. We show that a simple eligibility-weighted Hebbian learning rule, operating within a sensorimotor loop during motor explorations and stabilized by heterosynaptic competition, naturally gives rise to mirror neurons as well as control theoretic inverse models encoded in the synaptic weights from sensory to motor neurons. Crucially, we find that the correlational structure or stereotypy of the neural code underlying motor explorations determines the nature of the learned inverse model: random motor codes lead to causal inverses that map sensory activity patterns to their motor causes; such inverses are maximally useful, by allowing the imitation of arbitrary sensory target sequences. By contrast, stereotyped motor codes lead to less useful predictive inverses that map sensory activity to future motor actions. Our theory generalizes previous work on inverse models by showing that such models can be learned in a simple Hebbian framework without the need for error signals or backpropagation, and it makes new conceptual connections between the causal nature of inverse models, the statistical structure of motor variability, and the time-lag between sensory and motor responses of mirror neurons. Applied to bird song learning, our theory can account for puzzling aspects of the song system, including necessity of sensorimotor gating and selectivity of auditory responses to bird's own song (BOS) stimuli.

A Hebbian learning rule gives rise to mirror neurons and links them to control theoretic inverse models

PubMed Central

Hanuschkin, A.; Ganguli, S.; Hahnloser, R. H. R.

2013-01-01

Mirror neurons are neurons whose responses to the observation of a motor act resemble responses measured during production of that act. Computationally, mirror neurons have been viewed as evidence for the existence of internal inverse models. Such models, rooted within control theory, map-desired sensory targets onto the motor commands required to generate those targets. To jointly explore both the formation of mirrored responses and their functional contribution to inverse models, we develop a correlation-based theory of interactions between a sensory and a motor area. We show that a simple eligibility-weighted Hebbian learning rule, operating within a sensorimotor loop during motor explorations and stabilized by heterosynaptic competition, naturally gives rise to mirror neurons as well as control theoretic inverse models encoded in the synaptic weights from sensory to motor neurons. Crucially, we find that the correlational structure or stereotypy of the neural code underlying motor explorations determines the nature of the learned inverse model: random motor codes lead to causal inverses that map sensory activity patterns to their motor causes; such inverses are maximally useful, by allowing the imitation of arbitrary sensory target sequences. By contrast, stereotyped motor codes lead to less useful predictive inverses that map sensory activity to future motor actions. Our theory generalizes previous work on inverse models by showing that such models can be learned in a simple Hebbian framework without the need for error signals or backpropagation, and it makes new conceptual connections between the causal nature of inverse models, the statistical structure of motor variability, and the time-lag between sensory and motor responses of mirror neurons. Applied to bird song learning, our theory can account for puzzling aspects of the song system, including necessity of sensorimotor gating and selectivity of auditory responses to bird's own song (BOS) stimuli. PMID:23801941

Temperature dependence of DC transport characteristics for a two-dimensional electron gas in an undoped Si/SiGe heterostructure

NASA Astrophysics Data System (ADS)

Chou, Kuan-Yu; Hsu, Nai-Wen; Su, Yi-Hsin; Chou, Chung-Tao; Chiu, Po-Yuan; Chuang, Yen; Li, Jiun-Yun

2018-02-01

We investigate DC characteristics of a two-dimensional electron gas (2DEG) in an undoped Si/SiGe heterostructure and its temperature dependence. An insulated-gate field-effect transistor was fabricated, and transfer characteristics were measured at 4 K-300 K. At low temperatures (T < 45 K), source electrons are injected into the buried 2DEG channel first and drain current increases with the gate voltage. By increasing the gate voltage further, the current saturates followed by a negative transconductance observed, which can be attributed to electron tunneling from the buried channel to the surface channel. Finally, the drain current is saturated again at large gate biases due to parallel conduction of buried and surface channels. By increasing the temperature, an abrupt increase in threshold voltage is observed at T ˜ 45 K and it is speculated that negatively charged impurities at the Al2O3/Si interface are responsible for the threshold voltage shift. At T > 45 K, the current saturation and negative transconductance disappear and the device acts as a normal transistor.

Electrical characteristic fluctuation of 16-nm-gate high-κ/metal gate bulk FinFET devices in the presence of random interface traps

NASA Astrophysics Data System (ADS)

Hsu, Sheng-Chia; Li, Yiming

2014-11-01

In this work, we study the impact of random interface traps (RITs) at the interface of SiO x /Si on the electrical characteristic of 16-nm-gate high-κ/metal gate (HKMG) bulk fin-type field effect transistor (FinFET) devices. Under the same threshold voltage, the effects of RIT position and number on the degradation of electrical characteristics are clarified with respect to different levels of RIT density of state ( D it). The variability of the off-state current ( I off) and drain-induced barrier lowering (DIBL) will be severely affected by RITs with high D it varying from 5 × 1012 to 5 × 1013 eV-1 cm-2 owing to significant threshold voltage ( V th) fluctuation. The results of this study indicate that if the level of D it is lower than 1 × 1012 eV-1 cm-2, the normalized variability of the on-state current, I off, V th, DIBL, and subthreshold swing is within 5%.

Carbon nanotube feedback-gate field-effect transistor: suppressing current leakage and increasing on/off ratio.

PubMed

Qiu, Chenguang; Zhang, Zhiyong; Zhong, Donglai; Si, Jia; Yang, Yingjun; Peng, Lian-Mao

2015-01-27

Field-effect transistors (FETs) based on moderate or large diameter carbon nanotubes (CNTs) usually suffer from ambipolar behavior, large off-state current and small current on/off ratio, which are highly undesirable for digital electronics. To overcome these problems, a feedback-gate (FBG) FET structure is designed and tested. This FBG FET differs from normal top-gate FET by an extra feedback-gate, which is connected directly to the drain electrode of the FET. It is demonstrated that a FBG FET based on a semiconducting CNT with a diameter of 1.5 nm may exhibit low off-state current of about 1 × 10(-13) A, high current on/off ratio of larger than 1 × 10(8), negligible drain-induced off-state leakage current, and good subthreshold swing of 75 mV/DEC even at large source-drain bias and room temperature. The FBG structure is promising for CNT FETs to meet the standard for low-static-power logic electronics applications, and could also be utilized for building FETs using other small band gap semiconductors to suppress leakage current.

Deletion of striatal adenosine A2A receptor spares latent inhibition and prepulse inhibition but impairs active avoidance learning

PubMed Central

Singer, Philipp; Wei, Catherine J.; Chen, Jiang-Fan; Boison, Detlev; Yee, Benjamin K.

2013-01-01

Following early clinical leads, the adenosine A2AR receptor (A2AR) has continued to attract attention as a potential novel target for treating schizophrenia; especially against the negative and cognitive symptoms of the disease because of A2AR’s unique modulatory action over glutamatergic in addition to dopaminergic signaling. Through the antagonistic interaction with the dopamine D2 receptor, and by regulating glutamate release and N-methyl-d-aspartate receptor function, striatal A2AR is ideally positioned to fine-tune the dopamine-glutamate balance whose disturbance is implicated in the pathophysiology of schizophrenia. However, the precise function of striatal A2ARsin the regulation of schizophrenia-relevant behavior is poorly understood. Here, we tested the impact of conditional striatum-specific A2AR knockout (st-A2AR-KO) on latent inhibition (LI) and prepulse inhibition (PPI) – behavior that is tightly regulated by striatal dopamine and glutamate. These are two common cross-species translational tests for the assessment of selective attention and sensorimotor gating deficits reported in schizophrenia patients; and enhanced performance in these tests is associated with antipsychotic drug action. We found that neither LI nor PPI was significantly affected in st-A2AR-KO mice; although a deficit in active avoidance learning was identified in these animals. The latter phenotype, however, was not replicated in another form of aversive conditioning – conditioned taste aversion. Hence, the present study shows that neither learned inattention (as measured by LI) nor sensory gating (as indexed by PPI) requires the integrity of striatal A2ARs– a finding that may undermine the hypothesized importance of A2AR in the genesis and/or treatment of schizophrenia. PMID:23276608

Calibration approach for fluorescence lifetime determination for applications using time-gated detection and finite pulse width excitation.

PubMed

Keller, Scott B; Dudley, Jonathan A; Binzel, Katherine; Jasensky, Joshua; de Pedro, Hector Michael; Frey, Eric W; Urayama, Paul

2008-10-15

Time-gated techniques are useful for the rapid sampling of excited-state (fluorescence) emission decays in the time domain. Gated detectors coupled with bright, economical, nanosecond-pulsed light sources like flashlamps and nitrogen lasers are an attractive combination for bioanalytical and biomedical applications. Here we present a calibration approach for lifetime determination that is noniterative and that does not assume a negligible instrument response function (i.e., a negligible excitation pulse width) as does most current rapid lifetime determination approaches. Analogous to a transducer-based sensor, signals from fluorophores of known lifetime (0.5-12 ns) serve as calibration references. A fast avalanche photodiode and a GHz-bandwidth digital oscilloscope is used to detect transient emission from reference samples excited using a nitrogen laser. We find that the normalized time-integrated emission signal is proportional to the lifetime, which can be determined with good reproducibility (typically <100 ps) even for data with poor signal-to-noise ratios ( approximately 20). Results are in good agreement with simulations. Additionally, a new time-gating scheme for fluorescence lifetime imaging applications is proposed. In conclusion, a calibration-based approach is a valuable analysis tool for the rapid determination of lifetime in applications using time-gated detection and finite pulse width excitation.

Behavioral Assessment of Spaceflight Effects on Neurocognitive Performance - Extent and Longevity

NASA Technical Reports Server (NTRS)

De Dios, Y.E.; Kofman, I.S.; Gadd, N.E.; Kreutzberg, G.A.; Peters, B.T.; Taylor, L.C.; Campbell, D.J.; Wood, S.J.; Bloomberg, J.J.; Seidler, R.D.;

Tactile Sensory Supplementation of Gravitational References to Optimize Sensorimotor Recovery

NASA Technical Reports Server (NTRS)

Black, F. O.; Paloski, W. H.; Bloomberg, J. J.; Wood, S. J.

2007-01-01

Integration of multi-sensory inputs to detect tilts relative to gravity is critical for sensorimotor control of upright orientation. Displaying body orientation using electrotactile feedback to the tongue has been developed by Bach-y- Rita and colleagues as a sensory aid to maintain upright stance with impaired vestibular feedback. This investigation has explored the effects of Tongue Elecrotactile Feedback (TEF) for control of posture and movement as a sensorimotor countermeasure, specifically addressing the optimal location of movement sensors.

Hand Sensorimotor Function in Older Children With Neonatal Brachial Plexus Palsy.

PubMed

Brown, Susan H; Wernimont, Cory W; Phillips, Lauren; Kern, Kathy L; Nelson, Virginia S; Yang, Lynda J-S

2016-03-01

Routine sensory assessments in neonatal brachial plexus palsy are infrequently performed because it is generally assumed that sensory recovery exceeds motor recovery. However, studies examining sensory function in neonatal brachial plexus palsy have produced equivocal findings. The purpose of this study was to examine hand sensorimotor function in older children with neonatal brachial plexus palsy using standard clinical and research-based measures of tactile sensibility. Seventeen children with neonatal brachial plexus palsy (mean age: 11.6 years) and 19 age-matched controls participated in the study. Functional assessments included grip force, monofilament testing, and hand dexterity (Nine-Hole Peg, Jebsen-Taylor Hand Function). Tactile spatial perception involving the discrimination of pin patterns and movement-enhanced object recognition (stereognosis) were also assessed. In the neonatal brachial plexus palsy group, significant deficits in the affected hand motor function were observed compared with the unaffected hand. Median monofilament scores were considered normal for both hands. In contrast, tactile spatial perception was impaired in the neonatal brachial plexus palsy group. This impairment was seen as deficits in both pin pattern and object recognition accuracy as well as the amount of time required to identify patterns and objects. Tactile pattern discrimination time significantly correlated with performance on both functional assessment tests (P < 0.01). This study provides evidence that tactile perception deficits may accompany motor deficits in neonatal brachial plexus palsy even when measures of tactile registration (i.e., monofilament testing) are normal. These results may reflect impaired processing of somatosensory feedback associated with reductions in goal-directed upper limb use and illustrate the importance of including a broader range of sensory assessments in neonatal brachial plexus palsy. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2012-03-01

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

Functional brain imaging of a complex navigation task following one night of total sleep deprivation

NASA Technical Reports Server (NTRS)

Strangman, Gary; Thompson, John H.; Strauss, Monica M.; Marshburn, Thomas H.; Sutton, Jeffrey P.

2006-01-01

Study Objectives: To assess the cerebral effects associated with sleep deprivation in a simulation of a complex, real-world, high-risk task. Design and Interventions: A two-week, repeated measures, cross-over experimental protocol, with counterbalanced orders of normal sleep (NS) and total sleep deprivation (TSD). Setting: Each subject underwent functional magnetic resonance imaging (fMRI) while performing a dual-joystick, 3D sensorimotor navigation task (simulated orbital docking). Scanning was performed twice per subject, once following a night of normal sleep (NS), and once following a single night of total sleep deprivation (TSD). Five runs (eight 24s docking trials each) were performed during each scanning session. Participants: Six healthy, young, right-handed volunteers (2 women; mean age 20) participated. Measurements and Results: Behavioral performance on multiple measures was comparable in the two sleep conditions. Neuroimaging results within sleep conditions revealed similar locations of peak activity for NS and TSD, including left sensorimotor cortex, left precuneus (BA 7), and right visual areas (BA 18/19). However, cerebral activation following TSD was substantially larger and exhibited higher amplitude modulations from baseline. When directly comparing NS and TSD, most regions exhibited TSD>NS activity, including multiple prefrontal cortical areas (BA 8/9,44/45,47), lateral parieto-occipital areas (BA 19/39, 40), superior temporal cortex (BA 22), and bilateral thalamus and amygdala. Only left parietal cortex (BA 7) demonstrated NS>TSD activity. Conclusions: The large network of cerebral differences between the two conditions, even with comparable behavioral performance, suggests the possibility of detecting TSD-induced stress via functional brain imaging techniques on complex tasks before stress-induced failures.

AlN/GaN heterostructures for normally-off transistors

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

Zhuravlev, K. S., E-mail: zhur@isp.nsc.ru; Malin, T. V.; Mansurov, V. G.

The structure of AlN/GaN heterostructures with an ultrathin AlN barrier is calculated for normally-off transistors. The molecular-beam epitaxy technology of in situ passivated SiN/AlN/GaN heterostructures with a two-dimensional electron gas is developed. Normally-off transistors with a maximum current density of ~1 A/mm, a saturation voltage of 1 V, a transconductance of 350 mS/mm, and a breakdown voltage of more than 60 V are demonstrated. Gate lag and drain lag effects are almost lacking in these transistors.

The impact of adult vitamin D deficiency on behaviour and brain function in male Sprague-Dawley rats.

PubMed

Byrne, Jacqueline H; Voogt, Meggie; Turner, Karly M; Eyles, Darryl W; McGrath, John J; Burne, Thomas H J

2013-01-01

Vitamin D deficiency is common in the adult population, and this has been linked to depression and cognitive outcomes in clinical populations. The aim of this study was to investigate the effects of adult vitamin D (AVD) deficiency on behavioural tasks of relevance to neuropsychiatric disorders in male Sprague-Dawley rats. Ten-week old male Sprague-Dawley rats were fed a control or vitamin D deficient diet for 6 weeks prior to, and during behavioural testing. We first examined a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception. We then assessed locomotor response to the psychomimetic drugs, amphetamine and MK-801. Attention and vigilance were assessed using the 5 choice serial reaction time task (5C-SRT) and the 5 choice continuous performance task (5C-CPT) and, in a separate cohort, working memory was assessed using the delay match to sample (DMTS) task. We also examined excitatory and inhibitory neurotransmitters in prefrontal cortex and striatum. AVD-deficient rats were deficient in vitamin D3 (<10 nM) and had normal calcium and phosphate levels after 8-10 weeks on the diet. Overall, AVD deficiency was not associated with an altered phenotype across the range of behavioural domains tested. On the 5C-SRT AVD-deficient rats made more premature responses and more head entries during longer inter-trial intervals (ITI) than control rats. On the 5C-CPT AVD-deficient rats took longer to make false alarm (FA) responses than control rats. AVD-deficient rats had increases in baseline GABA levels and the ratio of DOPAC/HVA within the striatum. AVD-deficient rats exhibited no major impairments in any of the behavioural domains tested. Impairments in premature responses in AVD-deficient rats may indicate that these animals have specific alterations in striatal systems governing compulsive or reward-seeking behaviour.

p53 activated by AND gate genetic circuit under radiation and hypoxia for targeted cancer gene therapy.

PubMed

Ding, Miao; Li, Rong; He, Rong; Wang, Xingyong; Yi, Qijian; Wang, Weidong

2015-09-01

Radio-activated gene therapy has been developed as a novel therapeutic strategy against cancer; however, expression of therapeutic gene in peritumoral tissues will result in unacceptable toxicity to normal cells. To restrict gene expression in targeted tumor mass, we used hypoxia and radiation tolerance features of tumor cells to develop a synthetic AND gate genetic circuit through connecting radiation sensitivity promoter cArG6 , heat shock response elements SNF1, HSF1 and HSE4 with retroviral vector plxsn. Their construction and dynamic activity process were identified through downstream enhanced green fluorescent protein and wtp53 expression in non-small cell lung cancer A549 cells and in a nude mice model. The result showed that AND gate genetic circuit could be activated by lower required radiation dose (6 Gy) and after activated, AND gate could induce significant apoptosis effects and growth inhibition of cancer cells in vitro and in vivo. The radiation- and hypoxia-activated AND gate genetic circuit, which could lead to more powerful target tumoricidal activity represented a promising strategy for both targeted and effective gene therapy of human lung adenocarcinoma and low dose activation character of the AND gate genetic circuit implied that this model could be further exploited to decrease side-effects of clinical radiation therapy. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Effect of Context and Hearing Loss on Time-Gated Word Recognition in Children

PubMed Central

Lewis, Dawna E.; Kopun, Judy; McCreery, Ryan; Brennan, Marc; Nishi, Kanae; Cordrey, Evan; Stelmachowicz, Pat; Moeller, Mary Pat

2016-01-01

Objectives The purpose of this study was to examine word recognition in children who are hard of hearing (CHH) and children with normal hearing (CNH) in response to time-gated words presented in high- vs. low-predictability sentences (HP, LP), where semantic cues were manipulated. Findings inform our understanding of how CHH combine cognitive-linguistic and acoustic-phonetic cues to support spoken word recognition. It was hypothesized that both groups of children would be able to make use of linguistic cues provided by HP sentences to support word recognition. CHH were expected to require greater acoustic information (more gates) than CNH to correctly identify words in the LP condition. In addition, it was hypothesized that error patterns would differ across groups. Design Sixteen CHH with mild-to-moderate hearing loss and 16 age-matched CNH participated (5–12 yrs). Test stimuli included 15 LP and 15 HP age-appropriate sentences. The final word of each sentence was divided into segments and recombined with the sentence frame to create series of sentences in which the final word was progressively longer by the gated increments. Stimuli were presented monaurally through headphones and children were asked to identify the target word at each successive gate. They also were asked to rate their confidence in their word choice using a 5- or 3-point scale. For CHH, the signals were processed through a hearing aid simulator. Standardized language measures were used to assess the contribution of linguistic skills. Results Analysis of language measures revealed that the CNH and CHH performed within the average range on language abilities. Both groups correctly recognized a significantly higher percentage of words in the HP condition than in the LP condition. Although CHH performed comparably to CNH in terms of successfully recognizing the majority of words, differences were observed in the amount of acoustic-phonetic information needed to achieve accurate word recognition. CHH needed more gates than CNH to identify words in the LP condition. CNH were significantly lower in rating their confidence in the LP condition than in the HP condition. CHH, however, were not significantly different in confidence between the conditions. Error patterns for incorrect word responses across gates and predictability varied depending on hearing status. Conclusions The results of this study suggest that CHH with age-appropriate language abilities took advantage of context cues in the HP sentences to guide word recognition in a manner similar to CNH. However, in the LP condition, they required more acoustic information (more gates) than CNH for word recognition. Differences in the structure of incorrect word responses and their nomination patterns across gates for CHH compared to their peers with normal hearing suggest variations in how these groups use limited acoustic information to select word candidates. PMID:28045838

Fast activation of dihydropyridine-sensitive calcium channels of skeletal muscle. Multiple pathways of channel gating

PubMed Central

1996-01-01

Dihydropyridine (DHP) receptors of the transverse tubule membrane play two roles in excitation-contraction coupling in skeletal muscle: (a) they function as the voltage sensor which undergoes fast transition to control release of calcium from sarcoplasmic reticulum, and (b) they provide the conducting unit of a slowly activating L-type calcium channel. To understand this dual function of the DHP receptor, we studied the effect of depolarizing conditioning pulse on the activation kinetics of the skeletal muscle DHP-sensitive calcium channels reconstituted into lipid bilayer membranes. Activation of the incorporated calcium channel was imposed by depolarizing test pulses from a holding potential of -80 mV. The gating kinetics of the channel was studied with ensemble averages of repeated episodes. Based on a first latency analysis, two distinct classes of channel openings occurred after depolarization: most had delayed latencies, distributed with a mode of 70 ms (slow gating); a small number of openings had short first latencies, < 12 ms (fast gating). A depolarizing conditioning pulse to +20 mV placed 200 ms before the test pulse (-10 mV), led to a significant increase in the activation rate of the ensemble averaged-current; the time constant of activation went from tau m = 110 ms (reference) to tau m = 45 ms after conditioning. This enhanced activation by the conditioning pulse was due to the increase in frequency of fast open events, which was a steep function of the intermediate voltage and the interval between the conditioning pulse and the test pulse. Additional analysis demonstrated that fast gating is the property of the same individual channels that normally gate slowly and that the channels adopt this property after a sojourn in the open state. The rapid secondary activation seen after depolarizing prepulses is not compatible with a linear activation model for the calcium channel, but is highly consistent with a cyclical model. A six- state cyclical model is proposed for the DHP-sensitive Ca channel, which pictures the normal pathway of activation of the calcium channel as two voltage-dependent steps in sequence, plus a voltage-independent step which is rate limiting. The model reproduced well the fast and slow gating models of the calcium channel, and the effects of conditioning pulses. It is possible that the voltage-sensitive gating transitions of the DHP receptor, which occur early in the calcium channel activation sequence, could underlie the role of the voltage sensor and yield the rapid excitation-contraction coupling in skeletal muscle, through either electrostatic or allosteric linkage to the ryanodine receptors/calcium release channels. PMID:8882865

Sensorimotor Skills and Language Comprehension in Autistic Children.

ERIC Educational Resources Information Center

Sigman, Marian; Ungerer, Judy

1981-01-01

The fact that the autistic children were so impaired in language even with fairly good sensorimotor skills suggests that these skills, particularly object permanence, play a minor role in their language acquisition. (Author)

Visuomotor coordination and cortical connectivity of modular motor learning.

PubMed

Burgos, Pablo I; Mariman, Juan J; Makeig, Scott; Rivera-Lillo, Gonzalo; Maldonado, Pedro E

2018-05-15

The ability to transfer sensorimotor skill components to new actions and the capacity to use skill components from whole actions are characteristic of the adaptability of the human sensorimotor system. However, behavioral evidence suggests complex limitations for transfer after combined or modular learning of motor adaptations. Also, to date, only behavioral analysis of the consequences of the modular learning has been reported, with little understanding of the sensorimotor mechanisms of control and the interaction between cortical areas. We programmed a video game with distorted kinematic and dynamic features to test the ability to combine sensorimotor skill components learned modularly (composition) and the capacity to use separate sensorimotor skill components learned in combination (decomposition). We examined motor performance, eye-hand coordination, and EEG connectivity. When tested for integrated learning, we found that combined practice initially performed better than separated practice, but differences disappeared after integrated practice. Separate learning promotes fewer anticipatory control mechanisms (depending more on feedback control), evidenced in a lower gaze leading behavior and in higher connectivity between visual and premotor domains, in comparison with the combined practice. The sensorimotor system can acquire motor modules in a separated or integrated manner. However, the system appears to require integrated practice to coordinate the adaptations with the skill learning and the networks involved in the integrated behavior. This integration seems to be related to the acquisition of anticipatory mechanism of control and with the decrement of feedback control. © 2018 Wiley Periodicals, Inc.

Hand-in-hand advances in biomedical engineering and sensorimotor restoration.

PubMed

Pisotta, Iolanda; Perruchoud, David; Ionta, Silvio

2015-05-15

Living in a multisensory world entails the continuous sensory processing of environmental information in order to enact appropriate motor routines. The interaction between our body and our brain is the crucial factor for achieving such sensorimotor integration ability. Several clinical conditions dramatically affect the constant body-brain exchange, but the latest developments in biomedical engineering provide promising solutions for overcoming this communication breakdown. The ultimate technological developments succeeded in transforming neuronal electrical activity into computational input for robotic devices, giving birth to the era of the so-called brain-machine interfaces. Combining rehabilitation robotics and experimental neuroscience the rise of brain-machine interfaces into clinical protocols provided the technological solution for bypassing the neural disconnection and restore sensorimotor function. Based on these advances, the recovery of sensorimotor functionality is progressively becoming a concrete reality. However, despite the success of several recent techniques, some open issues still need to be addressed. Typical interventions for sensorimotor deficits include pharmaceutical treatments and manual/robotic assistance in passive movements. These procedures achieve symptoms relief but their applicability to more severe disconnection pathologies is limited (e.g. spinal cord injury or amputation). Here we review how state-of-the-art solutions in biomedical engineering are continuously increasing expectances in sensorimotor rehabilitation, as well as the current challenges especially with regards to the translation of the signals from brain-machine interfaces into sensory feedback and the incorporation of brain-machine interfaces into daily activities. Copyright © 2015 Elsevier B.V. All rights reserved.

Changes in resting-state connectivity in musicians with embouchure dystonia.

PubMed

Haslinger, Bernhard; Noé, Jonas; Altenmüller, Eckart; Riedl, Valentin; Zimmer, Claus; Mantel, Tobias; Dresel, Christian

2017-03-01

Embouchure dystonia is a highly disabling task-specific dystonia in professional brass musicians leading to spasms of perioral muscles while playing the instrument. As they are asymptomatic at rest, resting-state functional magnetic resonance imaging in these patients can reveal changes in functional connectivity within and between brain networks independent from dystonic symptoms. We therefore compared embouchure dystonia patients to healthy musicians with resting-state functional magnetic resonance imaging in combination with independent component analyses. Patients showed increased functional connectivity of the bilateral sensorimotor mouth area and right secondary somatosensory cortex, but reduced functional connectivity of the bilateral sensorimotor hand representation, left inferior parietal cortex, and mesial premotor cortex within the lateral motor function network. Within the auditory function network, the functional connectivity of bilateral secondary auditory cortices, right posterior parietal cortex and left sensorimotor hand area was increased, the functional connectivity of right primary auditory cortex, right secondary somatosensory cortex, right sensorimotor mouth representation, bilateral thalamus, and anterior cingulate cortex was reduced. Negative functional connectivity between the cerebellar and lateral motor function network and positive functional connectivity between the cerebellar and primary visual network were reduced. Abnormal resting-state functional connectivity of sensorimotor representations of affected and unaffected body parts suggests a pathophysiological predisposition for abnormal sensorimotor and audiomotor integration in embouchure dystonia. Altered connectivity to the cerebellar network highlights the important role of the cerebellum in this disease. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Effects of rotation on the sleep state-dependent midlatency auditory evoked P50 potential in the human

NASA Technical Reports Server (NTRS)

Dornhoffer, John L.; Mamiya, N.; Bray, P.; Skinner, Robert D.; Garcia-Rill, Edgar

2002-01-01

Sopite syndrome, characterized by loss of initiative, sensitivity to normally innocuous sensory stimuli, and impaired concentration amounting to a sensory gating deficit, is commonly associated with Space Motion Sickness (SMS). The amplitude of the P50 potential is a measure of level of arousal, and a paired-stimulus paradigm can be used to measure sensory gating. We used the rotary chair to elicit the sensory mismatch that occurs with SMS by overstimulating the vestibular apparatus. The effects of rotation on the manifestation of the P50 midlatency auditory evoked response were then assessed as a measure of arousal and distractibility. Results showed that rotation-induced motion sickness produced no change in the level of arousal but did produce a significant deficit in sensory gating, indicating that some of the attentional and cognitive deficits observed with SMS may be due to distractibility induced by decreased habituation to repetitive stimuli.

Gate-Tunable Spin Transport and Giant Electroresistance in Ferromagnetic Graphene Vertical Heterostructures

PubMed Central

Myoung, Nojoon; Park, Hee Chul; Lee, Seung Joo

2016-01-01

Controlling tunneling properties through graphene vertical heterostructures provides advantages in achieving large conductance modulation which has been known as limitation in lateral graphene device structures. Despite of intensive research on graphene vertical heterosturctures for recent years, the potential of spintronics based on graphene vertical heterostructures remains relatively unexplored. Here, we present an analytical device model for graphene-based spintronics by using ferromagnetic graphene in vertical heterostructures. We consider a normal or ferroelectric insulator as a tunneling layer. The device concept yields a way of controlling spin transport through the vertical heterostructures, resulting in gate-tunable spin-switching phenomena. Also, we revealed that a ‘giant’ resistance emerges through a ferroelectric insulating layer owing to the anti-parallel configuration of ferromagnetic graphene layers by means of electric fields via gate and bias voltages. Our findings discover the prospect of manipulating the spin transport properties in vertical heterostructures without use of magnetic fields. PMID:27126101

Loss of VGLUT3 Produces Circadian-Dependent Hyperdopaminergia and Ameliorates Motor Dysfunction and l-Dopa-Mediated Dyskinesias in a Model of Parkinson's Disease

PubMed Central

Divito, Christopher B.; Steece-Collier, Kathy; Case, Daniel T.; Williams, Sean-Paul G.; Stancati, Jennifer A.; Zhi, Lianteng; Rubio, Maria E.; Sortwell, Caryl E.; Collier, Timothy J.; Sulzer, David; Edwards, Robert H.; Zhang, Hui

2015-01-01

The striatum is essential for many aspects of mammalian behavior, including motivation and movement, and is dysfunctional in motor disorders such as Parkinson's disease. The vesicular glutamate transporter 3 (VGLUT3) is expressed by striatal cholinergic interneurons (CINs) and is thus well positioned to regulate dopamine (DA) signaling and locomotor activity, a canonical measure of basal ganglia output. We now report that VGLUT3 knock-out (KO) mice show circadian-dependent hyperlocomotor activity that is restricted to the waking cycle and is due to an increase in striatal DA synthesis, packaging, and release. Using a conditional VGLUT3 KO mouse, we show that deletion of the transporter from CINs, surprisingly, does not alter evoked DA release in the dorsal striatum or baseline locomotor activity. The mice do, however, display changes in rearing behavior and sensorimotor gating. Elevation of DA release in the global KO raised the possibility that motor deficits in a Parkinson's disease model would be reduced. Remarkably, after a partial 6-hydroxydopamine (6-OHDA)-mediated DA depletion (∼70% in dorsal striatum), KO mice, in contrast to WT mice, showed normal motor behavior across the entire circadian cycle. l-3,4-dihydroxyphenylalanine-mediated dyskinesias were also significantly attenuated. These findings thus point to new mechanisms to regulate basal ganglia function and potentially treat Parkinson's disease and related disorders. SIGNIFICANCE STATEMENT Dopaminergic signaling is critical for both motor and cognitive functions in the mammalian nervous system. Impairments, such as those found in Parkinson's disease patients, can lead to severe motor deficits. Vesicular glutamate transporter 3 (VGLUT3) loads glutamate into secretory vesicles for neurotransmission and is expressed by discrete neuron populations throughout the nervous system. Here, we report that the absence of VGLUT3 in mice leads to an upregulation of the midbrain dopamine system. Remarkably, in a Parkinson's disease model, the mice show normal motor behavior. They also show fewer abnormal motor behaviors (dyskinesias) in response to l-3,4-dihydroxyphenylalanine, the principal treatment for Parkinson's disease. The work thus suggests new avenues for the development of novel treatment strategies for Parkinson's disease and potentially other basal-ganglia-related disorders. PMID:26558771

A statistical model of catheter motion from interventional x-ray images: application to image-based gating

NASA Astrophysics Data System (ADS)

Panayiotou, M.; King, A. P.; Ma, Y.; Housden, R. J.; Rinaldi, C. A.; Gill, J.; Cooklin, M.; O'Neill, M.; Rhode, K. S.

2013-11-01

The motion and deformation of catheters that lie inside cardiac structures can provide valuable information about the motion of the heart. In this paper we describe the formation of a novel statistical model of the motion of a coronary sinus (CS) catheter based on principal component analysis of tracked electrode locations from standard mono-plane x-ray fluoroscopy images. We demonstrate the application of our model for the purposes of retrospective cardiac and respiratory gating of x-ray fluoroscopy images in normal dose x-ray fluoroscopy images, and demonstrate how a modification of the technique allows application to very low dose scenarios. We validated our method on ten mono-plane imaging sequences comprising a total of 610 frames from ten different patients undergoing radiofrequency ablation for the treatment of atrial fibrillation. For normal dose images we established systole, end-inspiration and end-expiration gating with success rates of 100%, 92.1% and 86.9%, respectively. For very low dose applications, the method was tested on the same ten mono-plane x-ray fluoroscopy sequences without noise and with added noise at signal to noise ratio (SNR) values of √50, √10, √8, √6, √5, √2 and √1 to simulate the image quality of increasingly lower dose x-ray images. The method was able to detect the CS catheter even in the lowest SNR images with median errors not exceeding 2.6 mm per electrode. Furthermore, gating success rates of 100%, 71.4% and 85.7% were achieved at the low SNR value of √2, representing a dose reduction of more than 25 times. Thus, the technique has the potential to extract useful information whilst substantially reducing the radiation exposure.

Preservation of perceptual integration improves temporal stability of bimanual coordination in the elderly: an evidence of age-related brain plasticity.

PubMed

Blais, Mélody; Martin, Elodie; Albaret, Jean-Michel; Tallet, Jessica

2014-12-15

Despite the apparent age-related decline in perceptual-motor performance, recent studies suggest that the elderly people can improve their reaction time when relevant sensory information are available. However, little is known about which sensory information may improve motor behaviour itself. Using a synchronization task, the present study investigates how visual and/or auditory stimulations could increase accuracy and stability of three bimanual coordination modes produced by elderly and young adults. Neurophysiological activations are recorded with ElectroEncephaloGraphy (EEG) to explore neural mechanisms underlying behavioural effects. Results reveal that the elderly stabilize all coordination modes when auditory or audio-visual stimulations are available, compared to visual stimulation alone. This suggests that auditory stimulations are sufficient to improve temporal stability of rhythmic coordination, even more in the elderly. This behavioural effect is primarily associated with increased attentional and sensorimotor-related neural activations in the elderly but similar perceptual-related activations in elderly and young adults. This suggests that, despite a degradation of attentional and sensorimotor neural processes, perceptual integration of auditory stimulations is preserved in the elderly. These results suggest that perceptual-related brain plasticity is, at least partially, conserved in normal aging. Copyright © 2014 Elsevier B.V. All rights reserved.

Artificial gravity as a countermeasure for mitigating physiological deconditioning during long-duration space missions.

PubMed

Clément, Gilles R; Bukley, Angelia P; Paloski, William H

2015-01-01

In spite of the experience gained in human space flight since Yuri Gagarin's historical flight in 1961, there has yet to be identified a completely effective countermeasure for mitigating the effects of weightlessness on humans. Were astronauts to embark upon a journey to Mars today, the 6-month exposure to weightlessness en route would leave them considerably debilitated, even with the implementation of the suite of piece-meal countermeasures currently employed. Continuous or intermittent exposure to simulated gravitational states on board the spacecraft while traveling to and from Mars, also known as artificial gravity, has the potential for enhancing adaptation to Mars gravity and re-adaptation to Earth gravity. Many physiological functions are adversely affected by the weightless environment of spaceflight because they are calibrated for normal, Earth's gravity. Hence, the concept of artificial gravity is to provide a broad-spectrum replacement for the gravitational forces that naturally occur on the Earth's surface, thereby avoiding the physiological deconditioning that takes place in weightlessness. Because researchers have long been concerned by the adverse sensorimotor effects that occur in weightlessness as well as in rotating environments, additional study of the complex interactions among sensorimotor and other physiological systems in rotating environments must be undertaken both on Earth and in space before artificial gravity can be implemented.

Functional Network Development During the First Year: Relative Sequence and Socioeconomic Correlations

PubMed Central

Gao, Wei; Alcauter, Sarael; Elton, Amanda; Hernandez-Castillo, Carlos R.; Smith, J. Keith; Ramirez, Juanita; Lin, Weili

2015-01-01

The first postnatal year is characterized by the most dramatic functional network development of the human lifespan. Yet, the relative sequence of the maturation of different networks and the impact of socioeconomic status (SES) on their development during this critical period remains poorly characterized. Leveraging a large, normally developing infant sample with multiple longitudinal resting-state functional magnetic resonance imaging scans during the first year (N = 65, scanned every 3 months), we aimed to delineate the relative maturation sequence of 9 key brain functional networks and examine their SES correlations. Our results revealed a maturation sequence from primary sensorimotor/auditory to visual to attention/default-mode, and finally to executive control networks. Network-specific critical growth periods were also identified. Finally, marginally significant positive SES–brain correlations were observed at 6 months of age for both the sensorimotor and default-mode networks, indicating interesting SES effects on functional brain maturation. To the best of our knowledge, this is the first study delineating detailed longitudinal growth trajectories of all major functional networks during the first year of life and their SES correlations. Insights from this study not only improve our understanding of early brain development, but may also inform the critical periods for SES expression during infancy. PMID:24812084

Experimental Traumatic Brain Injury Results in Long-Term Recovery of Functional Responsiveness in Sensory Cortex but Persisting Structural Changes and Sensorimotor, Cognitive, and Emotional Deficits.

PubMed

Johnstone, Victoria P A; Wright, David K; Wong, Kendrew; O'Brien, Terence J; Rajan, Ramesh; Shultz, Sandy R

2015-09-01

Traumatic brain injury (TBI) is a leading cause of death worldwide. In recent studies, we have shown that experimental TBI caused an immediate (24-h post) suppression of neuronal processing, especially in supragranular cortical layers. We now examine the long-term effects of experimental TBI on the sensory cortex and how these changes may contribute to a range of TBI morbidities. Adult male Sprague-Dawley rats received either a moderate lateral fluid percussion injury (n=14) or a sham surgery (n=12) and 12 weeks of recovery before behavioral assessment, magnetic resonance imaging, and electrophysiological recordings from the barrel cortex. TBI rats demonstrated sensorimotor deficits, cognitive impairments, and anxiety-like behavior, and this was associated with significant atrophy of the barrel cortex and other brain structures. Extracellular recordings from ipsilateral barrel cortex revealed normal neuronal responsiveness and diffusion tensor MRI showed increased fractional anisotropy, axial diffusivity, and tract density within this region. These findings suggest that long-term recovery of neuronal responsiveness is owing to structural reorganization within this region. Therefore, it is likely that long-term structural and functional changes within sensory cortex post-TBI may allow for recovery of neuronal responsiveness, but that this recovery does not remediate all behavioral deficits.

Sensorimotor learning configures the human mirror system.

PubMed

Catmur, Caroline; Walsh, Vincent; Heyes, Cecilia

2007-09-04

Cells in the "mirror system" fire not only when an individual performs an action but also when one observes the same action performed by another agent [1-4]. The mirror system, found in premotor and parietal cortices of human and monkey brains, is thought to provide the foundation for social understanding and to enable the development of theory of mind and language [5-9]. However, it is unclear how mirror neurons acquire their mirror properties -- how they derive the information necessary to match observed with executed actions [10]. We address this by showing that it is possible to manipulate the selectivity of the human mirror system, and thereby make it operate as a countermirror system, by giving participants training to perform one action while observing another. Before this training, participants showed event-related muscle-specific responses to transcranial magnetic stimulation over motor cortex during observation of little- and index-finger movements [11-13]. After training, this normal mirror effect was reversed. These results indicate that the mirror properties of the mirror system are neither wholly innate [14] nor fixed once acquired; instead they develop through sensorimotor learning [15, 16]. Our findings indicate that the human mirror system is, to some extent, both a product and a process of social interaction.

Explicit and Implicit Processes Constitute the Fast and Slow Processes of Sensorimotor Learning.

PubMed

McDougle, Samuel D; Bond, Krista M; Taylor, Jordan A

2015-07-01

A popular model of human sensorimotor learning suggests that a fast process and a slow process work in parallel to produce the canonical learning curve (Smith et al., 2006). Recent evidence supports the subdivision of sensorimotor learning into explicit and implicit processes that simultaneously subserve task performance (Taylor et al., 2014). We set out to test whether these two accounts of learning processes are homologous. Using a recently developed method to assay explicit and implicit learning directly in a sensorimotor task, along with a computational modeling analysis, we show that the fast process closely resembles explicit learning and the slow process approximates implicit learning. In addition, we provide evidence for a subdivision of the slow/implicit process into distinct manifestations of motor memory. We conclude that the two-state model of motor learning is a close approximation of sensorimotor learning, but it is unable to describe adequately the various implicit learning operations that forge the learning curve. Our results suggest that a wider net be cast in the search for the putative psychological mechanisms and neural substrates underlying the multiplicity of processes involved in motor learning. Copyright © 2015 the authors 0270-6474/15/359568-12$15.00/0.

Neurodevelopmental perspectives on dance learning: Insights from early adolescence and young adulthood.

PubMed

Sumanapala, Dilini K; Walbrin, Jon; Kirsch, Louise P; Cross, Emily S

2018-01-01

Studies investigating human motor learning and movement perception have shown that similar sensorimotor brain regions are engaged when we observe or perform action sequences. However, the way these networks enable translation of complex observed actions into motor commands-such as in the context of dance-remains poorly understood. Emerging evidence suggests that the ability to encode specific visuospatial and kinematic movement properties encountered via different routes of sensorimotor experience may be an integral component of action learning throughout development. Using a video game-based dance training paradigm, we demonstrate that patterns of voxel activity in visual and sensorimotor brain regions when perceiving movements following training are related to the sensory modalities through which these movements were encountered during whole-body dance training. Compared to adolescents, young adults in this study demonstrated more distinctive patterns of voxel activity in visual cortices in relation to different types of sensorimotor experience. This finding suggests that cortical maturity might influence the extent to which prior sensorimotor experiences shape brain activity when watching others in action, and potentially impact how we acquire new motor skills. © 2018 Elsevier B.V. All rights reserved.

Altered contralateral sensorimotor system organization after experimental hemispherectomy: a structural and functional connectivity study.

PubMed

Otte, Willem M; van der Marel, Kajo; van Meer, Maurits P A; van Rijen, Peter C; Gosselaar, Peter H; Braun, Kees P J; Dijkhuizen, Rick M

2015-08-01

Hemispherectomy is often followed by remarkable recovery of cognitive and motor functions. This reflects plastic capacities of the remaining hemisphere, involving large-scale structural and functional adaptations. Better understanding of these adaptations may (1) provide new insights in the neuronal configuration and rewiring that underlies sensorimotor outcome restoration, and (2) guide development of rehabilitation strategies to enhance recovery after hemispheric lesioning. We assessed brain structure and function in a hemispherectomy model. With MRI we mapped changes in white matter structural integrity and gray matter functional connectivity in eight hemispherectomized rats, compared with 12 controls. Behavioral testing involved sensorimotor performance scoring. Diffusion tensor imaging and resting-state functional magnetic resonance imaging were acquired 7 and 49 days post surgery. Hemispherectomy caused significant sensorimotor deficits that largely recovered within 2 weeks. During the recovery period, fractional anisotropy was maintained and white matter volume and axial diffusivity increased in the contralateral cerebral peduncle, suggestive of preserved or improved white matter integrity despite overall reduced white matter volume. This was accompanied by functional adaptations in the contralateral sensorimotor network. The observed white matter modifications and reorganization of functional network regions may provide handles for rehabilitation strategies improving functional recovery following large lesions.

Explicit and Implicit Processes Constitute the Fast and Slow Processes of Sensorimotor Learning

PubMed Central

Bond, Krista M.; Taylor, Jordan A.

2015-01-01

A popular model of human sensorimotor learning suggests that a fast process and a slow process work in parallel to produce the canonical learning curve (Smith et al., 2006). Recent evidence supports the subdivision of sensorimotor learning into explicit and implicit processes that simultaneously subserve task performance (Taylor et al., 2014). We set out to test whether these two accounts of learning processes are homologous. Using a recently developed method to assay explicit and implicit learning directly in a sensorimotor task, along with a computational modeling analysis, we show that the fast process closely resembles explicit learning and the slow process approximates implicit learning. In addition, we provide evidence for a subdivision of the slow/implicit process into distinct manifestations of motor memory. We conclude that the two-state model of motor learning is a close approximation of sensorimotor learning, but it is unable to describe adequately the various implicit learning operations that forge the learning curve. Our results suggest that a wider net be cast in the search for the putative psychological mechanisms and neural substrates underlying the multiplicity of processes involved in motor learning. PMID:26134640

How infants' reaches reveal principles of sensorimotor decision making

NASA Astrophysics Data System (ADS)

Dineva, Evelina; Schöner, Gregor

2018-01-01

In Piaget's classical A-not-B-task, infants repeatedly make a sensorimotor decision to reach to one of two cued targets. Perseverative errors are induced by switching the cue from A to B, while spontaneous errors are unsolicited reaches to B when only A is cued. We argue that theoretical accounts of sensorimotor decision-making fail to address how motor decisions leave a memory trace that may impact future sensorimotor decisions. Instead, in extant neural models, perseveration is caused solely by the history of stimulation. We present a neural dynamic model of sensorimotor decision-making within the framework of Dynamic Field Theory, in which a dynamic instability amplifies fluctuations in neural activation into macroscopic, stable neural activation states that leave memory traces. The model predicts perseveration, but also a tendency to repeat spontaneous errors. To test the account, we pool data from several A-not-B experiments. A conditional probabilities analysis accounts quantitatively how motor decisions depend on the history of reaching. The results provide evidence for the interdependence among subsequent reaching decisions that is explained by the model, showing that by amplifying small differences in activation and affecting learning, decisions have consequences beyond the individual behavioural act.

First third filling parameters of left ventricle assessed from gated equilibrium studies in patients with various heart diseases

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

Adatepe, M.H.; Nichols, K.; Powell, O.M.

1984-01-01

The authors determined the first third filling fraction (1/3 FF), the maximum filling rate (1/3 FR) and the mean filling rate (1/3 MFR) for the first third diastolic filling period of the left ventricle in patients with coronary artery disease (CAD), valvular heart disease (VHD), pericardial effusion (PE), cardiomyopathies (CM), chronic obstructive lung disease (COPD) and in 5 normals-all from resting gated equilibrium studies. Parameters are calculated from the third order Fourier fit to the LV volume curve and its derivative. 1/3 FF% = 1/3 diastolic count - end systolic count / 1/3 diastolic count x 100. Patients with CADmore » are divided into two groups: Group I with normal ejection fraction (EF) and wall motion (WM); Group II with abnormal EF and WM. Results are shown in the table. Abnormal filling parameters are found not only in CAD but in VHD, PE and CM. The authors conclude that the first third LV filling parameters are sensitive but non-specific indicators of filling abnormalities caused by diverse etiologic factors. Abnormal first third filling parameters may occur in the presence of a normal resting EF and WM in CAD.« less

Enhancing Functional Performance using Sensorimotor Adaptability Training Programs

NASA Technical Reports Server (NTRS)

Bloomberg, J. J.; Mulavara, A. P.; Peters, B. T.; Brady, R.; Audas, C.; Ruttley, T. M.; Cohen, H. S.

2009-01-01

During the acute phase of adaptation to novel gravitational environments, sensorimotor disturbances have the potential to disrupt the ability of astronauts to perform functional tasks. The goal of this project is to develop a sensorimotor adaptability (SA) training program designed to facilitate recovery of functional capabilities when astronauts transition to different gravitational environments. The project conducted a series of studies that investigated the efficacy of treadmill training combined with a variety of sensory challenges designed to increase adaptability including alterations in visual flow, body loading, and support surface stability.

Human analog tests of the sixth stage of object permanence.

PubMed

Heishman, M; Conant, M; Pasnak, R

1995-06-01

Two adult cats were tested on multiple invisible displacement. A dowel was established as a secondary reinforcer and hidden in a manner similar to that used to assess the culmination of sensorimotor intelligence in human infants. Three other cats were tested on single invisible displacement, a simpler version of the task. For human infants, this task is used to assess the beginning of mental representation in the sixth and last stage of sensorimotor intelligence. The cats' searches on these tasks were consistent with representation of an unsensed object and fully developed sensorimotor intelligence.

Trends in sensorimotor research and countermeasures for exploration-class space flights.

PubMed

Shelhamer, Mark

2015-01-01

Research in the area of sensorimotor and neurovestibular function has played an important role in enabling human space flight. This role, however, is changing. One of the key aspects of sensorimotor function relevant to this role will build on its widespread connections with other physiological and psychological systems in the body. The firm knowledge base in this area can provide a strong platform to explore these interactions, which can also provide for the development of effective and efficient countermeasures to the deleterious effects of space flight.

3D cine magnetic resonance imaging of rat lung ARDS using gradient-modulated SWIFT with retrospective respiratory gating

NASA Astrophysics Data System (ADS)

Kobayashi, Naoharu; Lei, Jianxun; Utecht, Lynn; Garwood, Michael; Ingbar, David H.; Bhargava, Maneesh

2015-03-01

SWeep Imaging with Fourier Transformation (SWIFT) with gradient modulation and DC navigator retrospective gating is introduced as a 3D cine magnetic resonance imaging (MRI) method for the lung. In anesthetized normal rats, the quasi-simultaneous excitation and acquisition in SWIFT enabled extremely high sensitivity to the fast-decaying parenchymal signals (TE=~4 μs), which are invisible with conventional MRI techniques. Respiratory motion information was extracted from DC navigator signals and the SWIFT data were reconstructed to 3D cine images with 16 respiratory phases. To test this technique's capabilities, rats exposed to > 95% O2 for 60 hours for induction of acute respiratory distress syndrome (ARDS), were imaged and compared with normal rat lungs (N=7 and 5 for ARDS and normal groups, respectively). SWIFT images showed lung tissue density differences along the gravity direction. In the cine SWIFT images, a parenchymal signal drop at the inhalation phase was consistently observed for both normal and ARDS rats due to lung inflation (i.e. decrease of the proton density), but the drop was less for ARDS rats. Depending on the respiratory phase and lung region, the lungs from the ARDS rats showed 1-24% higher parenchymal signal intensities relative to the normal rat lungs, likely due to accumulated extravascular water (EVLW). Those results demonstrate that SWIFT has high enough sensitivity for detecting the lung proton density changes due to gravity, different phases of respiration and accumulation of EVLW in the rat ARDS lungs.

Self-Organized Criticality, Plasticity and Sensorimotor Coupling. Explorations with a Neurorobotic Model in a Behavioural Preference Task

PubMed Central

Aguilera, Miguel; Barandiaran, Xabier E.; Bedia, Manuel G.; Seron, Francisco

2015-01-01

During the last two decades, analysis of 1/ƒ noise in cognitive science has led to a considerable progress in the way we understand the organization of our mental life. However, there is still a lack of specific models providing explanations of how 1/ƒ noise is generated in coupled brain-body-environment systems, since existing models and experiments typically target either externally observable behaviour or isolated neuronal systems but do not address the interplay between neuronal mechanisms and sensorimotor dynamics. We present a conceptual model of a minimal neurorobotic agent solving a behavioural task that makes it possible to relate mechanistic (neurodynamic) and behavioural levels of description. The model consists of a simulated robot controlled by a network of Kuramoto oscillators with homeostatic plasticity and the ability to develop behavioural preferences mediated by sensorimotor patterns. With only three oscillators, this simple model displays self-organized criticality in the form of robust 1/ƒ noise and a wide multifractal spectrum. We show that the emergence of self-organized criticality and 1/ƒ noise in our model is the result of three simultaneous conditions: a) non-linear interaction dynamics capable of generating stable collective patterns, b) internal plastic mechanisms modulating the sensorimotor flows, and c) strong sensorimotor coupling with the environment that induces transient metastable neurodynamic regimes. We carry out a number of experiments to show that both synaptic plasticity and strong sensorimotor coupling play a necessary role, as constituents of self-organized criticality, in the generation of 1/ƒ noise. The experiments also shown to be useful to test the robustness of 1/ƒ scaling comparing the results of different techniques. We finally discuss the role of conceptual models as mediators between nomothetic and mechanistic models and how they can inform future experimental research where self-organized critically includes sensorimotor coupling among the essential interaction-dominant process giving rise to 1/ƒ noise. PMID:25706744

Beta-band activity and connectivity in sensorimotor and parietal cortex are important for accurate motor performance.

PubMed

Chung, Jae W; Ofori, Edward; Misra, Gaurav; Hess, Christopher W; Vaillancourt, David E

2017-01-01

Accurate motor performance may depend on the scaling of distinct oscillatory activity within the motor cortex and effective neural communication between the motor cortex and other brain areas. Oscillatory activity within the beta-band (13-30Hz) has been suggested to provide distinct functional roles for attention and sensorimotor control, yet it remains unclear how beta-band and other oscillatory activity within and between cortical regions is coordinated to enhance motor performance. We explore this open issue by simultaneously measuring high-density cortical activity and elbow flexor and extensor neuromuscular activity during ballistic movements, and manipulating error using high and low visual gain across three target distances. Compared with low visual gain, high visual gain decreased movement errors at each distance. Group analyses in 3D source-space revealed increased theta-, alpha-, and beta-band desynchronization of the contralateral motor cortex and medial parietal cortex in high visual gain conditions and this corresponded to reduced movement error. Dynamic causal modeling was used to compute connectivity between motor cortex and parietal cortex. Analyses revealed that gain affected the directionally-specific connectivity across broadband frequencies from parietal to sensorimotor cortex but not from sensorimotor cortex to parietal cortex. These new findings provide support for the interpretation that broad-band oscillations in theta, alpha, and beta frequency bands within sensorimotor and parietal cortex coordinate to facilitate accurate upper limb movement. Our findings establish a link between sensorimotor oscillations in the context of online motor performance in common source space across subjects. Specifically, the extent and distinct role of medial parietal cortex to sensorimotor beta connectivity and local domain broadband activity combine in a time and frequency manner to assist ballistic movements. These findings can serve as a model to examine whether similar source space EEG dynamics exhibit different time-frequency changes in individuals with neurological disorders that cause movement errors. Copyright © 2016 Elsevier Inc. All rights reserved.

The integration of probabilistic information during sensorimotor estimation is unimpaired in children with Cerebral Palsy

PubMed Central

Sokhey, Taegh; Gaebler-Spira, Deborah; Kording, Konrad P.

2017-01-01

Background It is important to understand the motor deficits of children with Cerebral Palsy (CP). Our understanding of this motor disorder can be enriched by computational models of motor control. One crucial stage in generating movement involves combining uncertain information from different sources, and deficits in this process could contribute to reduced motor function in children with CP. Healthy adults can integrate previously-learned information (prior) with incoming sensory information (likelihood) in a close-to-optimal way when estimating object location, consistent with the use of Bayesian statistics. However, there are few studies investigating how children with CP perform sensorimotor integration. We compare sensorimotor estimation in children with CP and age-matched controls using a model-based analysis to understand the process. Methods and findings We examined Bayesian sensorimotor integration in children with CP, aged between 5 and 12 years old, with Gross Motor Function Classification System (GMFCS) levels 1–3 and compared their estimation behavior with age-matched typically-developing (TD) children. We used a simple sensorimotor estimation task which requires participants to combine probabilistic information from different sources: a likelihood distribution (current sensory information) with a prior distribution (learned target information). In order to examine sensorimotor integration, we quantified how participants weighed statistical information from the two sources (prior and likelihood) and compared this to the statistical optimal weighting. We found that the weighing of statistical information in children with CP was as statistically efficient as that of TD children. Conclusions We conclude that Bayesian sensorimotor integration is not impaired in children with CP and therefore, does not contribute to their motor deficits. Future research has the potential to enrich our understanding of motor disorders by investigating the stages of motor processing set out by computational models. Therapeutic interventions should exploit the ability of children with CP to use statistical information. PMID:29186196

Early self-managed focal sensorimotor rehabilitative training enhances functional mobility and sensorimotor function in patients following total knee replacement: a controlled clinical trial.

PubMed

Moutzouri, Maria; Gleeson, Nigel; Coutts, Fiona; Tsepis, Elias; John, Gliatis

2018-02-01

To assess the effects of early self-managed focal sensorimotor training compared to functional exercise training after total knee replacement on functional mobility and sensorimotor function. A single-blind controlled clinical trial. University Hospital of Rion, Greece. A total of 52 participants following total knee replacement. The primary outcome was the Timed Up and Go Test and the secondary outcomes were balance, joint position error, the Knee Outcome Survey Activities of Daily Living Scale, and pain. Patients were assessed on three separate occasions (presurgery, 8 weeks post surgery, and 14 weeks post surgery). Participants were randomized to either focal sensorimotor exercise training (experimental group) or functional exercise training (control group). Both groups received a 12-week home-based programme prescribed for 3-5 sessions/week (35-45 minutes). Consistently greater improvements ( F 2,98  = 4.3 to 24.8; P < 0.05) in group mean scores favour the experimental group compared to the control group: Timed Up and Go (7.8 ± 2.9 seconds vs. 4.6 ± 2.6 seconds); balance (2.1 ± 0.9° vs. 0.7 ± 1.2°); joint position error (13.8 ± 7.3° vs. 6.2 ± 9.1°); Knee Outcome Survey Activities of Daily Living Scale (44.2 ± 11.3 vs. 26.1 ± 11.4); and pain (5.9 ± 1.3 cm vs. 4.6 ± 1.1 cm). Patterns of improvement for the experimental group over time were represented by a relative effect size range of 1.3-6.5. Overall, the magnitude of improvements in functional mobility and sensorimotor function endorses using focal sensorimotor training as an effective mode of rehabilitation following knee replacement.

Spaceflight Sensorimotor Analogs: Simulating Acute and Adaptive Effects

NASA Technical Reports Server (NTRS)

Taylor, Laura C.; Harm, Deborah L.; Kozlovskaya, Inessa; Reschke, Millard F.; Wood, Scott J.

2009-01-01

Adaptive changes in sensorimotor function during spaceflight are reflected by spatial disorientation, motion sickness, gaze destabilization and decrements in balance, locomotion and eye-hand coordination that occur during and following transitions between different gravitational states. The purpose of this study was to conduct a meta-synthesis of data from spaceflight analogs to evaluate their effectiveness in simulating adaptive changes in sensorimotor function. METHODS. The analogs under review were categorized as either acute analogs used to simulate performance decrements accompanied with transient changes, or adaptive analogs used to drive sensorimotor learning to altered sensory feedback. The effectiveness of each analog was evaluated in terms of mechanisms of action, magnitude and time course of observed deficits compared to spaceflight data, and the effects of amplitude and exposure duration. RESULTS. Parabolic flight has been used extensively to examine effects of acute variation in gravitational loads, ranging from hypergravity to microgravity. More recently, galvanic vestibular stimulation has been used to elicit acute postural, locomotor and gaze dysfunction by disrupting vestibular afferents. Patient populations, e.g., with bilateral vestibular loss or cerebellar dysfunction, have been proposed to model acute sensorimotor dysfunction. Early research sponsored by NASA involved living onboard rotating rooms, which appeared to approximate the time course of adaptation and post-exposure recovery observed in astronauts following spaceflight. Exposure to different bed-rest paradigms (6 deg head down, dry immersion) result in similar motor deficits to that observed following spaceflight. Shorter adaptive analogs have incorporated virtual reality environments, visual distortion paradigms, exposure to conflicting tilt-translation cues, and exposure to 3Gx centrifugation. As with spaceflight, there is considerable variability in responses to most of the analogs reviewed. DISCUSSION. A true ground-based flight analog for sensorimotor function is not feasible. A combination of flight analogs; however, can be used to selectively mimic different aspects of the spaceflight-induced sensorimotor performance decrements.

Validity of semi-quantitative scale for brain MRI in unilateral cerebral palsy due to periventricular white matter lesions: Relationship with hand sensorimotor function and structural connectivity

PubMed Central

Fiori, Simona; Guzzetta, Andrea; Pannek, Kerstin; Ware, Robert S.; Rossi, Giuseppe; Klingels, Katrijn; Feys, Hilde; Coulthard, Alan; Cioni, Giovanni; Rose, Stephen; Boyd, Roslyn N.

2015-01-01

Aim To provide first evidence of construct validity of a semi-quantitative scale for brain structural MRI (sqMRI scale) in children with unilateral cerebral palsy (UCP) secondary to periventricular white matter (PWM) lesions, by examining the relationship with hand sensorimotor function and whole brain structural connectivity. Methods Cross-sectional study of 50 children with UCP due to PWM lesions using 3 T (MRI), diffusion MRI and assessment of hand sensorimotor function. We explored the relationship of lobar, hemispheric and global scores on the sqMRI scale, with fractional anisotropy (FA), as a measure of brain white matter microstructure, and with hand sensorimotor measures (Assisting Hand Assessment, AHA; Jebsen–Taylor Test for Hand Function, JTTHF; Melbourne Assessment of Unilateral Upper Limb Function, MUUL; stereognosis; 2-point discrimination). Results Lobar and hemispheric scores on the sqMRI scale contralateral to the clinical side of hemiplegia correlated with sensorimotor paretic hand function measures and FA of a number of brain structural connections, including connections of brain areas involved in motor control (postcentral, precentral and paracentral gyri in the parietal lobe). More severe lesions correlated with lower sensorimotor performance, with the posterior limb of internal capsule score being the strongest contributor to impaired hand function. Conclusion The sqMRI scale demonstrates first evidence of construct validity against impaired motor and sensory function measures and brain structural connectivity in a cohort of children with UCP due to PWM lesions. More severe lesions correlated with poorer paretic hand sensorimotor function and impaired structural connectivity in the hemisphere contralateral to the clinical side of hemiplegia. The quantitative structural MRI scoring may be a useful clinical tool for studying brain structure–function relationships but requires further validation in other populations of CP. PMID:26106533

Pre-flight sensorimotor adaptation protocols for suborbital flight.

PubMed

Shelhamer, Mark; Beaton, Kara

2012-01-01

Commercial suborbital flights, which include 3-5 minutes of 0 g between hyper-g launch and landing phases, will present suborbital passengers with a challenging sensorimotor experience. Based on the results of neurovestibular research in parabolic and orbital flight, and the anticipated wide range of fitness and experience levels of suborbital passengers, neurovestibular disturbances are likely to be problematic in this environment. Pre-flight adaptation protocols might alleviate some of these issues. Therefore, we describe a set of sensorimotor tests to evaluate passengers before suborbital flight, including assessment of the angular vestibulo-ocular reflex (VOR), ocular skew and disconjugate torsion, subjective visual vertical, and roll vection. Performance on these tests can be examined for correlations with in-flight experience, such as motion sickness, disorientation, and visual disturbances, based on questionnaires and cabin video recordings. Through an understanding of sensorimotor adaptation to parabolic and orbital flight, obtained from many previous studies, we can then suggest appropriate pre-flight adaptation procedures.

The effect of action video game playing on sensorimotor learning: Evidence from a movement tracking task.

PubMed

Gozli, Davood G; Bavelier, Daphne; Pratt, Jay

2014-10-12

Research on the impact of action video game playing has revealed performance advantages on a wide range of perceptual and cognitive tasks. It is not known, however, if playing such games confers similar advantages in sensorimotor learning. To address this issue, the present study used a manual motion-tracking task that allowed for a sensitive measure of both accuracy and improvement over time. When the target motion pattern was consistent over trials, gamers improved with a faster rate and eventually outperformed non-gamers. Performance between the two groups, however, did not differ initially. When the target motion was inconsistent, changing on every trial, results revealed no difference between gamers and non-gamers. Together, our findings suggest that video game playing confers no reliable benefit in sensorimotor control, but it does enhance sensorimotor learning, enabling superior performance in tasks with consistent and predictable structure. Copyright © 2014. Published by Elsevier B.V.

Mathematics reflecting sensorimotor organization.

PubMed

McCollum, Gin

2003-02-01

This review combines short presentations of several mathematical approaches that conceptualize issues in sensorimotor neuroscience from different perspectives and levels of analysis. The intricate organization of neural structures and sensorimotor performance calls for characterization using a variety of mathematical approaches. This review points out the prospects for mathematical neuroscience: in addition to computational approaches, there is a wide variety of mathematical approaches that provide insight into the organization of neural systems. By starting from the perspective that provides the greatest clarity, a mathematical approach avoids specificity that is inaccurate in characterizing the inherent biological organization. Approaches presented include the mathematics of ordered structures, motion-phase space, subject-coincident coordinates, equivalence classes, topological biodynamics, rhythm space metric, and conditional dynamics. Issues considered in this paper include unification of levels of analysis, response equivalence, convergence, relationship of physics to motor control, support of rhythms, state transitions, and focussing on low-dimensional subspaces of a high-dimensional sensorimotor space.

Induced sensorimotor brain plasticity controls pain in phantom limb patients

PubMed Central

Yanagisawa, Takufumi; Fukuma, Ryohei; Seymour, Ben; Hosomi, Koichi; Kishima, Haruhiko; Shimizu, Takeshi; Yokoi, Hiroshi; Hirata, Masayuki; Yoshimine, Toshiki; Kamitani, Yukiyasu; Saitoh, Youichi

2016-01-01

The cause of pain in a phantom limb after partial or complete deafferentation is an important problem. A popular but increasingly controversial theory is that it results from maladaptive reorganization of the sensorimotor cortex, suggesting that experimental induction of further reorganization should affect the pain, especially if it results in functional restoration. Here we use a brain–machine interface (BMI) based on real-time magnetoencephalography signals to reconstruct affected hand movements with a robotic hand. BMI training induces significant plasticity in the sensorimotor cortex, manifested as improved discriminability of movement information and enhanced prosthetic control. Contrary to our expectation that functional restoration would reduce pain, the BMI training with the phantom hand intensifies the pain. In contrast, BMI training designed to dissociate the prosthetic and phantom hands actually reduces pain. These results reveal a functional relevance between sensorimotor cortical plasticity and pain, and may provide a novel treatment with BMI neurofeedback. PMID:27807349

Limitations of threshold voltage engineering of AlGaN/GaN heterostructures by dielectric interface charge density and manipulation by oxygen plasma surface treatments

NASA Astrophysics Data System (ADS)

Lükens, G.; Yacoub, H.; Kalisch, H.; Vescan, A.

2016-05-01

The interface charge density between the gate dielectric and an AlGaN/GaN heterostructure has a significant impact on the absolute value and stability of the threshold voltage Vth of metal-insulator-semiconductor (MIS) heterostructure field effect transistor. It is shown that a dry-etching step (as typically necessary for normally off devices engineered by gate-recessing) before the Al2O3 gate dielectric deposition introduces a high positive interface charge density. Its origin is most likely donor-type trap states shifting Vth to large negative values, which is detrimental for normally off devices. We investigate the influence of oxygen plasma annealing techniques of the dry-etched AlGaN/GaN surface by capacitance-voltage measurements and demonstrate that the positive interface charge density can be effectively compensated. Furthermore, only a low Vth hysteresis is observable making this approach suitable for threshold voltage engineering. Analysis of the electrostatics in the investigated MIS structures reveals that the maximum Vth shift to positive voltages achievable is fundamentally limited by the onset of accumulation of holes at the dielectric/barrier interface. In the case of the Al2O3/Al0.26Ga0.74N/GaN material system, this maximum threshold voltage shift is limited to 2.3 V.

A Calibration Method for Nanowire Biosensors to Suppress Device-to-device Variation

PubMed Central

Ishikawa, Fumiaki N.; Curreli, Marco; Chang, Hsiao-Kang; Chen, Po-Chiang; Zhang, Rui; Cote, Richard J.; Thompson, Mark E.; Zhou, Chongwu

2009-01-01

Nanowire/nanotube biosensors have stimulated significant interest; however the inevitable device-to-device variation in the biosensor performance remains a great challenge. We have developed an analytical method to calibrate nanowire biosensor responses that can suppress the device-to-device variation in sensing response significantly. The method is based on our discovery of a strong correlation between the biosensor gate dependence (dIds/dVg) and the absolute response (absolute change in current, ΔI). In2O3 nanowire based biosensors for streptavidin detection were used as the model system. Studying the liquid gate effect and ionic concentration dependence of strepavidin sensing indicates that electrostatic interaction is the dominant mechanism for sensing response. Based on this sensing mechanism and transistor physics, a linear correlation between the absolute sensor response (ΔI) and the gate dependence (dIds/dVg) is predicted and confirmed experimentally. Using this correlation, a calibration method was developed where the absolute response is divided by dIds/dVg for each device, and the calibrated responses from different devices behaved almost identically. Compared to the common normalization method (normalization of the conductance/resistance/current by the initial value), this calibration method was proved advantageous using a conventional transistor model. The method presented here substantially suppresses device-to-device variation, allowing the use of nanosensors in large arrays. PMID:19921812

Auditory inhibitory gating in medial prefrontal cortex: Single unit and local field potential analysis.

PubMed

Mears, R P; Klein, A C; Cromwell, H C

2006-08-11

Medial prefrontal cortex is a crucial region involved in inhibitory processes. Damage to the medial prefrontal cortex can lead to loss of normal inhibitory control over motor, sensory, emotional and cognitive functions. The goal of the present study was to examine the basic properties of inhibitory gating in this brain region in rats. Inhibitory gating has recently been proposed as a neurophysiological assay for sensory filters in higher brain regions that potentially enable or disable information throughput. This perspective has important clinical relevance due to the findings that gating is dramatically impaired in individuals with emotional and cognitive impairments (i.e. schizophrenia). We used the standard inhibitory gating two-tone paradigm with a 500 ms interval between tones and a 10 s interval between tone pairs. We recorded both single unit and local field potentials from chronic microwire arrays implanted in the medial prefrontal cortex. We investigated short-term (within session) and long-term (between session) variability of auditory gating and additionally examined how altering the interval between the tones influenced the potency of the inhibition. The local field potentials displayed greater variability with a reduction in the amplitudes of the tone responses over both the short and long-term time windows. The decrease across sessions was most intense for the second tone response (test tone) leading to a more robust gating (lower T/C ratio). Surprisingly, single unit responses of different varieties retained similar levels of auditory responsiveness and inhibition in both the short and long-term analysis. Neural inhibition decreased monotonically related to the increase in intertone interval. This change in gating was most consistent in the local field potentials. Subsets of single unit responses did not show the lack of inhibition even for the longer intertone intervals tested (4 s interval). These findings support the idea that the medial prefrontal cortex is an important site where early inhibitory functions reside and potentially mediate psychological processes.

The influence of neck pain on sensorimotor function in the elderly.

PubMed

Uthaikhup, Sureeporn; Jull, Gwendolen; Sungkarat, Somporn; Treleaven, Julia

2012-01-01

Greater disturbances in sensorimotor control have been demonstrated in younger to middle aged groups. However, it is unknown whether or not the impairments documented in these populations can be extrapolated to elders with neck pain. The aim of this study was to investigate the influence of neck pain on sensorimotor function in elders. Twenty elders with neck pain (12 women and 8 men) and 20 healthy elder controls (14 women and 6 men) aged 65 years and over were recruited from the general community. Tests for sensorimotor function included; cervical joint position sense (JPS); computerised rod-and-frame test (RFT); smooth pursuit neck torsion test (SPNT); standing balance (under conditions of eyes open, eyes closed on firm and soft surfaces in comfortable stance); step test and ten-meter walk test with and without head movement. Elders with neck pain had greater deficits in the majority of sensorimotor function tests after controlling for effects of age and comorbidities. Significant differences were found in the SPNT (p<0.01), error in the RFT (frame angled at 10° and 15° anticlockwise) (p<0.05), standing balance (amplitude of sway) - eyes open on a firm surface in the medio-lateral (ML) direction (p=0.03), and total number of steps on the step test, both left and right sides (p<0.01). Elders with neck pain have greater sensorimotor disturbances than elders without neck pain, supporting a contribution of altered afferent information originating from the cervical spine to such disturbances. The findings may inform falls prevention and management programs. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Office management of gait disorders in the elderly

PubMed Central

Lam, Robert

2011-01-01

Abstract Objective To provide family physicians with an approach to office management of gait disorders in the elderly. Sources of information Ovid MEDLINE was searched from 1950 to July 2010 using subject headings for gait or neurologic gait disorders combined with physical examination. Articles specific to family practice or family physicians were selected. Relevant review articles and original research were used when appropriate and applicable to the elderly. Main message Gait and balance disorders in the elderly are difficult to recognize and diagnose in the family practice setting because they initially present with subtle undifferentiated manifestations, and because causes are usually multifactorial, with multiple diseases developing simultaneously. To further complicate the issue, these manifestations can be camouflaged in elderly patients by the physiologic changes associated with normal aging. A classification of gait disorders based on sensorimotor levels can be useful in the approach to management of this problem. Gait disorders in patients presenting to family physicians in the primary care setting are often related to joint and skeletal problems (lowest-level disturbances), as opposed to patients referred to neurology specialty clinics with sensory ataxia, myelopathy, multiple strokes, and parkinsonism (lowest-, middle-, and highest-level disturbances). The difficulty in diagnosing gait disorders stems from the challenge of addressing early undifferentiated disease caused by multiple disease processes involving all sensorimotor levels. Patients might present with a nonspecific “cautious” gait that is simply an adaptation of the body to disease limitations. This cautious gait has a mildly flexed posture with reduced arm swing and a broadening of the base of support. This article reviews the focused history (including medication review), practical physical examination, investigations, and treatments that are key to office management of gait disorders. Conclusion Family physicians will find it helpful to classify gait disorders based on sensorimotor level as part of their approach to office management of elderly patients. Managing gait disorders at early stages can help prevent further deconditioning and mobility impairment. PMID:21753097

GABA and glutamate levels correlate with MTR and clinical disability: Insights from multiple sclerosis.

PubMed

Nantes, Julia C; Proulx, Sébastien; Zhong, Jidan; Holmes, Scott A; Narayanan, Sridar; Brown, Robert A; Hoge, Richard D; Koski, Lisa

2017-08-15

Converging areas of research have implicated glutamate and γ-aminobutyric acid (GABA) as key players in neuronal signalling and other central functions. Further research is needed, however, to identify microstructural and behavioral links to regional variability in levels of these neurometabolites, particularly in the presence of demyelinating disease. Thus, we sought to investigate the extent to which regional glutamate and GABA levels are related to a neuroimaging marker of microstructural damage and to motor and cognitive performance. Twenty-one healthy volunteers and 47 people with multiple sclerosis (all right-handed) participated in this study. Motor and cognitive abilities were assessed with standard tests used in the study of multiple sclerosis. Proton magnetic resonance spectroscopy data were acquired from sensorimotor and parietal regions of the brains' left cerebral hemisphere using a MEGA-PRESS sequence. Our analysis protocol for the spectroscopy data was designed to account for confounding factors that could contaminate the measurement of neurometabolite levels due to disease, such as the macromolecule signal, partial volume effects, and relaxation effects. Glutamate levels in both regions of interest were lower in people with multiple sclerosis. In the sensorimotor (though not the parietal) region, GABA concentration was higher in the multiple sclerosis group compared to controls. Lower magnetization transfer ratio within grey and white matter regions from which spectroscopy data were acquired was linked to neurometabolite levels. When adjusting for age, normalized brain volume, MTR, total N-acetylaspartate level, and glutamate level, significant relationships were found between lower sensorimotor GABA level and worse performance on several tests, including one of upper limb motor function. This work highlights important methodological considerations relevant to analysis of spectroscopy data, particularly in the afflicted human brain. These findings support that regional neurotransmitter levels are linked to local microstructural integrity and specific behavioral abilities that can be affected in diseases such as multiple sclerosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Office management of gait disorders in the elderly.

PubMed

Lam, Robert

2011-07-01

To provide family physicians with an approach to office management of gait disorders in the elderly. Ovid MEDLINE was searched from 1950 to July 2010 using subject headings for gait or neurologic gait disorders combined with physical examination. Articles specific to family practice or family physicians were selected. Relevant review articles and original research were used when appropriate and applicable to the elderly. Gait and balance disorders in the elderly are difficult to recognize and diagnose in the family practice setting because they initially present with subtle undifferentiated manifestations, and because causes are usually multifactorial, with multiple diseases developing simultaneously. To further complicate the issue, these manifestations can be camouflaged in elderly patients by the physiologic changes associated with normal aging. A classification of gait disorders based on sensorimotor levels can be useful in the approach to management of this problem. Gait disorders in patients presenting to family physicians in the primary care setting are often related to joint and skeletal problems (lowest-level disturbances), as opposed to patients referred to neurology specialty clinics with sensory ataxia, myelopathy, multiple strokes, and parkinsonism (lowest-, middle-, and highest-level disturbances). The difficulty in diagnosing gait disorders stems from the challenge of addressing early undifferentiated disease caused by multiple disease processes involving all sensorimotor levels. Patients might present with a nonspecific "cautious" gait that is simply an adaptation of the body to disease limitations. This cautious gait has a mildly flexed posture with reduced arm swing and a broadening of the base of support. This article reviews the focused history (including medication review), practical physical examination, investigations, and treatments that are key to office management of gait disorders. Family physicians will find it helpful to classify gait disorders based on sensorimotor level as part of their approach to office management of elderly patients. Managing gait disorders at early stages can help prevent further deconditioning and mobility impairment.

Preserved pontine glucose metabolism in Alzheimer disease: A reference region for functional brain image (PET) analysis

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

Minoshima, Satoshi; Frey, K.A.; Foster, N.L.

1995-07-01

Our goal was to examine regional preservation of energy metabolism in Alzheimer disease (AD) and to evaluate effects of PET data normalization to reference regions. Regional metabolic rates in the pons, thalamus, putamen, sensorimotor cortex, visual cortex, and cerebellum (reference regions) were determined stereotaxically and examined in 37 patients with probable AD and 22 normal controls based on quantitative {sup 18}FDG-PET measurements. Following normalization of metabolic rates of the parietotemporal association cortex and whole brain to each reference region, distinctions of the two groups were assessed. The pons showed the best preservation of glucose metabolism in AD. Other reference regionsmore » showed relatively preserved metabolism compared with the parietotemporal association cortex and whole brain, but had significant metabolic reduction. Data normalization to the pons not only enhanced statistical significance of metabolic reduction in the parietotemporal association cortex, but also preserved the presence of global cerebral metabolic reduction indicated in analysis of the quantitative data. Energy metabolism in the pons in probable AD is well preserved. The pons is a reliable reference for data normalization and will enhance diagnostic accuracy and efficiency of quantitative and nonquantitative functional brain imaging. 39 refs., 2 figs., 3 tabs.« less

Comparison of the Effectiveness of Four Different Types of Needles in Irrigating Endodontically Treated Teeth.

DTIC Science & Technology

1980-02-08

3. Shih, M.; Marshall, F. J.; and Rosen, S. The bactericidal efficiency of sodium hypochlorite as an endodontic irrigant. Oral Surg 29(4): 613-619...and Rosen9 investi- gated the cleansing effect of sodium hypochlorite and normal saline on the apical one third using a standard irrigating method. They...found that sodium hypochlorite was no better than normal saline solutiun in irrigating this segment. Salzgeber and Brilliant10 investigated the

A neural network model of normal and abnormal auditory information processing.

PubMed

Du, X; Jansen, B H

2011-08-01

The ability of the brain to attenuate the response to irrelevant sensory stimulation is referred to as sensory gating. A gating deficiency has been reported in schizophrenia. To study the neural mechanisms underlying sensory gating, a neuroanatomically inspired model of auditory information processing has been developed. The mathematical model consists of lumped parameter modules representing the thalamus (TH), the thalamic reticular nucleus (TRN), auditory cortex (AC), and prefrontal cortex (PC). It was found that the membrane potential of the pyramidal cells in the PC module replicated auditory evoked potentials, recorded from the scalp of healthy individuals, in response to pure tones. Also, the model produced substantial attenuation of the response to the second of a pair of identical stimuli, just as seen in actual human experiments. We also tested the viewpoint that schizophrenia is associated with a deficit in prefrontal dopamine (DA) activity, which would lower the excitatory and inhibitory feedback gains in the AC and PC modules. Lowering these gains by less than 10% resulted in model behavior resembling the brain activity seen in schizophrenia patients, and replicated the reported gating deficits. The model suggests that the TRN plays a critical role in sensory gating, with the smaller response to a second tone arising from a reduction in inhibition of TH by the TRN. Copyright © 2011 Elsevier Ltd. All rights reserved.

Mechanism of oxide thickness and temperature dependent current conduction in n+-polySi/SiO2/p-Si structures — a new analysis

NASA Astrophysics Data System (ADS)

Samanta, Piyas

2017-10-01

The conduction mechanism of gate leakage current through thermally grown silicon dioxide (SiO2) films on (100) p-type silicon has been investigated in detail under negative bias on the degenerately doped n-type polysilicon (n+-polySi) gate. The analysis utilizes the measured gate current density J G at high oxide fields E ox in 5.4 to 12 nm thick SiO2 films between 25 and 300 °C. The leakage current measured up to 300 °C was due to Fowler-Nordheim (FN) tunneling of electrons from the accumulated n +-polySi gate in conjunction with Poole Frenkel (PF) emission of trapped-electrons from the electron traps located at energy levels ranging from 0.6 to 1.12 eV (depending on the oxide thickness) below the SiO2 conduction band (CB). It was observed that PF emission current I PF dominates FN electron tunneling current I FN at oxide electric fields E ox between 6 and 10 MV/cm and throughout the temperature range studied here. Understanding of the mechanism of leakage current conduction through SiO2 films plays a crucial role in simulation of time-dependent dielectric breakdown (TDDB) of metaloxide-semiconductor (MOS) devices and to precisely predict the normal operating field or applied gate voltage for lifetime projection of the MOS integrated circuits.

A combined coarse-grained and all-atom simulation of TRPV1 channel gating and heat activation

PubMed Central

Qin, Feng

2015-01-01

The transient receptor potential (TRP) channels act as key sensors of various chemical and physical stimuli in eukaryotic cells. Despite years of study, the molecular mechanisms of TRP channel activation remain unclear. To elucidate the structural, dynamic, and energetic basis of gating in TRPV1 (a founding member of the TRPV subfamily), we performed coarse-grained modeling and all-atom molecular dynamics (MD) simulation based on the recently solved high resolution structures of the open and closed form of TRPV1. Our coarse-grained normal mode analysis captures two key modes of collective motions involved in the TRPV1 gating transition, featuring a quaternary twist motion of the transmembrane domains (TMDs) relative to the intracellular domains (ICDs). Our transition pathway modeling predicts a sequence of structural movements that propagate from the ICDs to the TMDs via key interface domains (including the membrane proximal domain and the C-terminal domain), leading to sequential opening of the selectivity filter followed by the lower gate in the channel pore (confirmed by modeling conformational changes induced by the activation of ICDs). The above findings of coarse-grained modeling are robust to perturbation by lipids. Finally, our MD simulation of the ICD identifies key residues that contribute differently to the nonpolar energy of the open and closed state, and these residues are predicted to control the temperature sensitivity of TRPV1 gating. These computational predictions offer new insights to the mechanism for heat activation of TRPV1 gating, and will guide our future electrophysiology and mutagenesis studies. PMID:25918362

Resurgent current of voltage-gated Na+ channels

PubMed Central

Lewis, Amanda H; Raman, Indira M

2014-01-01

Resurgent Na+ current results from a distinctive form of Na+ channel gating, originally identified in cerebellar Purkinje neurons. In these neurons, the tetrodotoxin-sensitive voltage-gated Na+ channels responsible for action potential firing have specialized mechanisms that reduce the likelihood that they accumulate in fast inactivated states, thereby shortening refractory periods and permitting rapid, repetitive, and/or burst firing. Under voltage clamp, step depolarizations evoke transient Na+ currents that rapidly activate and quickly decay, and step repolarizations elicit slower channel reopening, or a ‘resurgent’ current. The generation of resurgent current depends on a factor in the Na+ channel complex, probably a subunit such as NaVβ4 (Scn4b), which blocks open Na+ channels at positive voltages, competing with the fast inactivation gate, and unblocks at negative voltages, permitting recovery from an open channel block along with a flow of current. Following its initial discovery, resurgent Na+ current has been found in nearly 20 types of neurons. Emerging research suggests that resurgent current is preferentially increased in a variety of clinical conditions associated with altered cellular excitability. Here we review the biophysical, molecular and structural mechanisms of resurgent current and their relation to the normal functions of excitable cells as well as pathophysiology. PMID:25172941

Cryo-EM maps reveal five-fold channel structures and their modification by gatekeeper mutations in the parvovirus minute virus of mice (MVM) capsid.

PubMed

Subramanian, Suriyasri; Organtini, Lindsey J; Grossman, Alec; Domeier, Phillip P; Cifuente, Javier O; Makhov, Alexander M; Conway, James F; D'Abramo, Anthony; Cotmore, Susan F; Tattersall, Peter; Hafenstein, Susan

2017-10-01

In minute virus of mice (MVM) capsids, icosahedral five-fold channels serve as portals mediating genome packaging, genome release, and the phased extrusion of viral peptides. Previous studies suggest that residues L172 and V40 are essential for channel function. The structures of MVMi wildtype, and mutant L172T and V40A virus-like particles (VLPs) were solved from cryo-EM data. Two constriction points, termed the mid-gate and inner-gate, were observed in the channels of wildtype particles, involving residues L172 and V40 respectively. While the mid-gate of V40A VLPs appeared normal, in L172T adjacent channel walls were altered, and in both mutants there was major disruption of the inner-gate, demonstrating that direct L172:V40 bonding is essential for its structural integrity. In wildtype particles, residues from the N-termini of VP2 map into claw-like densities positioned below the channel opening, which become disordered in the mutants, implicating both L172 and V40 in the organization of VP2 N-termini. Copyright © 2017 Elsevier Inc. All rights reserved.

Functional Task Test: 1. Sensorimotor changes Associated with Postflight Alterations in Astronaut Functional Task Performance

NASA Technical Reports Server (NTRS)

Bloomberg, J. J.; Arzeno, N. H.; Buxton, R. E.; Feiveson, A. H.; Kofman, I. S.; Lee, S. M. C.; Miller, C. A.; Mulavara, A. P.; Platts, S. H.; Peters, B. T.;

Sensorimotor-Independent Prefrontal Activity During Response Inhibition

PubMed Central

Cai, Weidong; Cannistraci, Christopher J.; Gore, John C.; Leung, Hoi-Chung

2015-01-01

A network of brain regions involving the ventral inferior frontal gyrus/anterior insula (vIFG/AI), presupplementary motor area (pre-SMA) and basal ganglia has been implicated in stopping impulsive, unwanted responses. However, whether this network plays an equal role in response inhibition under different sensorimotor contexts has not been tested systematically. Here, we conducted an fMRI experiment using the stop signal task, a sensorimotor task requiring occasional withholding of the planned response upon the presentation of a stop signal. We manipulated both the sensory modality of the stop signal (visual versus auditory) and the motor response modality (hand versus eye). Results showed that the vIFG/AI and the preSMA along with the right middle frontal gyrus were commonly activated in response inhibition across the various sensorimotor conditions. Our findings provide direct evidence for a common role of these frontal areas, but not striatal areas in response inhibition independent of the sensorimotor contexts. Nevertheless, these three frontal regions exhibited different activation patterns during successful and unsuccessful stopping. Together with the existing evidence, we suggest that the vIFG/AI is involved in the early stages of stopping such as triggering the stop process while the preSMA may play a role in regulating other cortical and subcortical regions involved in stopping. PMID:23798325

The Influence of Gravito-Inertial Force on Sensorimotor Integration and Reflexive Responses

NASA Technical Reports Server (NTRS)

Curthoys, Ian S.; Guedry, Fred E.; Merfeld, Daniel M.; Watt, Doug G. D.; Tomko, David L.; Wade, Charles E. (Technical Monitor)

1994-01-01

Sensorimotor responses (e.g.. eye movements, spinal reflexes, etc depend upon the interpretation of the neural signals from the sensory systems. Since neural signals from the otoliths may represent either tilt (gravity) or translation (linear inertial force), sensory signals from the otolith organs are necessarily somewhat ambiguous. Therefore. the neural responses to changing otolith signals depend upon the context of the stimulation (e.g- active vs. passive, relative orientation of gravity, etc.) as well as upon other sensory signals (e.g., vision. canals, etc.). This session will focus upon the -role -played by the sensory signals from the otolith organs in producing efficient sensorimotor and behavioral responses. Curthoys will show the influence of the peripheral anatomy and physiology. Tomko will discuss the influence of tilt and translational otolith signals on eye movements. Merfeld will demonstrate the rate otolith organs play during the interaction of sensory signals from the canals and otoliths. Watt will show the influence of the otoliths on spinal/postural responses. Guedry will discuss the contribution of vestibular information to "path of movement"' perception and to the development of a stable vertical reference. Sensorimotor responses to the ambiguous inertial force stimulation provide an important tool to investigate how the nervous system processes patterns of sensory information and yields functional sensorimotor responses.

Flexibility in embodied language understanding.

PubMed

Willems, Roel M; Casasanto, Daniel

2011-01-01

Do people use sensori-motor cortices to understand language? Here we review neurocognitive studies of language comprehension in healthy adults and evaluate their possible contributions to theories of language in the brain. We start by sketching the minimal predictions that an embodied theory of language understanding makes for empirical research, and then survey studies that have been offered as evidence for embodied semantic representations. We explore four debated issues: first, does activation of sensori-motor cortices during action language understanding imply that action semantics relies on mirror neurons? Second, what is the evidence that activity in sensori-motor cortices plays a functional role in understanding language? Third, to what extent do responses in perceptual and motor areas depend on the linguistic and extra-linguistic context? And finally, can embodied theories accommodate language about abstract concepts? Based on the available evidence, we conclude that sensori-motor cortices are activated during a variety of language comprehension tasks, for both concrete and abstract language. Yet, this activity depends on the context in which perception and action words are encountered. Although modality-specific cortical activity is not a sine qua non of language processing even for language about perception and action, sensori-motor regions of the brain appear to make functional contributions to the construction of meaning, and should therefore be incorporated into models of the neurocognitive architecture of language.

Trajectory formation principles are the same after mild or moderate stroke

PubMed Central

van Dokkum, Liesjet Elisabeth Henriette; Froger, Jérôme; Gouaïch, Abdelkader; Laffont, Isabelle

2017-01-01

When we make rapid reaching movements, we have to trade speed for accuracy. To do so, the trajectory of our hand is the result of an optimal balance between feed-forward and feed-back control in the face of signal-dependant noise in the sensorimotor system. How far do these principles of trajectory formation still apply after a stroke, for persons with mild to moderate sensorimotor deficits who recovered some reaching ability? Here, we examine the accuracy of fast hand reaching movements with a focus on the information capacity of the sensorimotor system and its relation to trajectory formation in young adults, in persons who had a stroke and in age-matched control participants. We find that persons with stroke follow the same trajectory formation principles, albeit parameterized differently in the face of higher sensorimotor uncertainty. Higher directional errors after a stroke result in less feed-forward control, hence more feed-back loops responsible for segmented movements. As a consequence, movements are globally slower to reach the imposed accuracy, and the information throughput of the sensorimotor system is lower after a stroke. The fact that the most abstract principles of motor control remain after a stroke suggests that clinicians can capitalize on existing theories of motor control and learning to derive principled rehabilitation strategies. PMID:28329000

Relationships Between Vestibular Measures as Potential Predictors for Spaceflight Sensorimotor Adaptation

NASA Technical Reports Server (NTRS)

Clark, T. K.; Peters, B.; Gadd, N. E.; De Dios, Y. E.; Wood, S.; Bloomberg, J. J.; Mulavara, A. P.

2016-01-01

Introduction: During space exploration missions astronauts are exposed to a series of novel sensorimotor environments, requiring sensorimotor adaptation. Until adaptation is complete, sensorimotor decrements occur, affecting critical tasks such as piloted landing or docking. Of particularly interest are locomotion tasks such as emergency vehicle egress or extra-vehicular activity. While nearly all astronauts eventually adapt sufficiently, it appears there are substantial individual differences in how quickly and effectively this adaptation occurs. These individual differences in capacity for sensorimotor adaptation are poorly understood. Broadly, we aim to identify measures that may serve as pre-flight predictors of and individual's adaptation capacity to spaceflight-induced sensorimotor changes. As a first step, since spaceflight is thought to involve a reinterpretation of graviceptor cues (e.g. otolith cues from the vestibular system) we investigate the relationships between various measures of vestibular function in humans. Methods: In a set of 15 ground-based control subjects, we quantified individual differences in vestibular function using three measures: 1) ocular vestibular evoked myogenic potential (oVEMP), 2) computerized dynamic posturography and 3) vestibular perceptual thresholds. oVEMP responses are elicited using a mechanical stimuli approach. Computerized dynamic posturography was used to quantify Sensory Organization Tests (SOTs), including SOT5M which involved performing pitching head movements while balancing on a sway-reference support surface with eyes closed. We implemented a vestibular perceptual threshold task using the tilt capabilities of the Tilt-Translation Sled (TTS) at JSC. On each trial, the subject was passively roll-tilted left ear down or right ear down in the dark and verbally provided a forced-choice response regarding which direction they felt tilted. The motion profile was a single-cycle sinusoid of angular acceleration with a duration of 5 seconds (frequency of 0.2 Hz), which was selected as it requires sensory integration of otolith and semicircular canal cues. Stimuli direction was randomized and magnitude was determined using an adaptive sampling procedure. One hundred trials were provided and each subject's responses were fit with a psychometric curve to estimate the subject's threshold. Results: Roll tilt perceptual thresholds at 0.2 Hz ranged from 0.5 degrees to 1.82 degrees across the 15 subjects (geometric mean of 1.04 degrees), consistent with previous studies. The inter-individual variability in thresholds may be able to help explain individual differences observed in sensorimotor adaptation to spaceflight. Analysis is ongoing for the oVEMPS and computerized dynamic posturography to identify relationships between the various vestibular measures. Discussion: Predicting individual differences in sensorimotor adaptation is critical both for the development of personalized countermeasures and mission planning. Here we aim to develop a basis of vestibular tests and parameters which may serve as predictors of individual differences in sensorimotor adaptability through studying the relationship between these measures.

Increased whole-body auditory startle reflex and autonomic reactivity in children with anxiety disorders

PubMed Central

Bakker, Mirte J.; Tijssen, Marina A.J.; van der Meer, Johan N.; Koelman, Johannes H.T.M.; Boer, Frits

2009-01-01

Background Young patients with anxiety disorders are thought to have a hypersensitive fear system, including alterations of the early sensorimotor processing of threatening information. However, there is equivocal support in auditory blink response studies for an enlarged auditory startle reflex (ASR) in such patients. We sought to investigate the ASR measured over multiple muscles (whole-body) in children and adolescents with anxiety disorders. Methods Between August and December 2006, we assessed ASRs (elicited by 8 consecutive tones of 104 dB, interstimulus interval of about 2 min) in 25 patients and 25 matched controls using a case–control design and in 9 nonaffected siblings. We recorded the electromyographic activity of 6 muscles and the sympathetic skin response. We investigated response occurrence (probability %) and response magnitude (area under the curve in μV × ms) of the combined response of 6 muscles and of the single blink response. Results In patients (17 girls, mean age 12 years; 13 social phobia, 9 generalized anxiety, 3 other), the combined response probability (p = 0.027) of all muscles, the combined area under the curve of all muscles (p = 0.011) and the sympathetic skin response (p = 0.006) were enlarged compared with matched controls. The response probability (p = 0.48) and area under the curve (p = 0.07) of the blink response were normal in patients compared with controls. The ASR pattern was normal with normal latencies in patients compared with controls. In nonaffected siblings, the sympathetic skin response (p = 0.038), but not the combined response probability of all muscles (p = 0.15), was enlarged compared with controls. Limitations Limitations are the sample size and restricted comparison to the psychophysiological ASR paradigm. Conclusion The results point toward a hypersensitive central nervous system (fear system), including early sensorimotor processing alterations and autonomic hyperreactivity. The multiple muscle (whole-body) ASR is suggested to be a better tool to detect ASR abnormalities in patients with anxiety disorders than the blink response alone. Abnormalities in ASR serve as a candidate endophenotype of anxiety disorders. PMID:19568483

Motor-skill learning in a novel running-wheel task is dependent on D1 dopamine receptors in the striatum

PubMed Central

Willuhn, Ingo; Steiner, Heinz

2008-01-01

Evidence indicates that dopamine receptors regulate processes of procedural learning in the sensorimotor striatum. Our previous studies revealed that the indirect dopamine receptor agonist cocaine alters motor-skill learning-associated gene regulation in the sensorimotor striatum. Cocaine-induced gene regulation in the striatum is principally mediated by D1 dopamine receptors. We investigated the effects of cocaine and striatal D1 receptor antagonism on motor-skill learning. Rats were trained on a running wheel (40–60 min, 2–5 days) to learn a new motor skill, that is, the ability to control the movement of the wheel. Immediately before each training session, the animals received an injection of vehicle or cocaine (25 mg/kg, i.p.), and/or the D1 receptor antagonist SCH-23390 (0, 3, 10 μg/kg, i.p., or 0, 0.3, 1 μg, intrastriatal via chronically implanted cannula). The animal’s ability to control/balance the moving wheel (wheel skill) was tested before and repeatedly after the training. Normal wheel-skill memory lasted for at least 4 weeks. Cocaine administered before the training tended to attenuate skill learning. Systemic administration of SCH-23390 alone also impaired skill learning. However, cocaine given in conjunction with the lower SCH-23390 dose (3 μg/kg) reversed the inhibition of skill learning produced by the D1 receptor antagonist, enabling intact skill performance during the whole post-training period. In contrast, when cocaine was administered with the higher SCH-23390 dose (10 μg/kg), skill performance was normalized 1–6 days after the training, but these rats lost their improved wheel skill by day 18 after the training. Similar effects were produced by SCH-23390 (0.3–1 μg) infused into the striatum. Our results indicate that cocaine interferes with normal motor-skill learning, which seems to be dependent on optimal D1 receptor signaling. Furthermore, our findings demonstrate that D1 receptors in the striatum are critical for consolidation of long-term skill memory. PMID:18343588

From prosodic structure to acoustic saliency: A fMRI investigation of speech rate, clarity, and emphasis

NASA Astrophysics Data System (ADS)

Golfinopoulos, Elisa

Acoustic variability in fluent speech can arise at many stages in speech production planning and execution. For example, at the phonological encoding stage, the grouping of phonemes into syllables determines which segments are coarticulated and, by consequence, segment-level acoustic variation. Likewise phonetic encoding, which determines the spatiotemporal extent of articulatory gestures, will affect the acoustic detail of segments. Functional magnetic resonance imaging (fMRI) was used to measure brain activity of fluent adult speakers in four speaking conditions: fast, normal, clear, and emphatic (or stressed) speech. These speech manner changes typically result in acoustic variations that do not change the lexical or semantic identity of productions but do affect the acoustic saliency of phonemes, syllables and/or words. Acoustic responses recorded inside the scanner were assessed quantitatively using eight acoustic measures and sentence duration was used as a covariate of non-interest in the neuroimaging analysis. Compared to normal speech, emphatic speech was characterized acoustically by a greater difference between stressed and unstressed vowels in intensity, duration, and fundamental frequency, and neurally by increased activity in right middle premotor cortex and supplementary motor area, and bilateral primary sensorimotor cortex. These findings are consistent with right-lateralized motor planning of prosodic variation in emphatic speech. Clear speech involved an increase in average vowel and sentence durations and average vowel spacing, along with increased activity in left middle premotor cortex and bilateral primary sensorimotor cortex. These findings are consistent with an increased reliance on feedforward control, resulting in hyper-articulation, under clear as compared to normal speech. Fast speech was characterized acoustically by reduced sentence duration and average vowel spacing, and neurally by increased activity in left anterior frontal operculum and posterior dorsal inferior frontal gyms pars opercularis -- regions thought to be involved in sequencing and phrase-level structural processing. Taken together these findings identify the acoustic and neural correlates of adjusting speech manner and underscore the different processing stages that can contribute to acoustic variability in fluent sentence production.

An Aversive Response to Osmotic Upshift in Caenorhabditis elegans

PubMed Central

Yu, Jingyi; Liu, He

2017-01-01

Abstract Environmental osmolarity presents a common type of sensory stimulus to animals. While behavioral responses to osmotic changes are important for maintaining a stable intracellular osmolarity, the underlying mechanisms are not fully understood. In the natural habitat of Caenorhabditis elegans, changes in environmental osmolarity are commonplace. It is known that the nematode acutely avoids shocks of extremely high osmolarity. Here, we show that C. elegans also generates gradually increased aversion of mild upshifts in environmental osmolarity. Different from an acute avoidance of osmotic shocks that depends on the function of a transient receptor potential vanilloid channel, the slow aversion to osmotic upshifts requires the cGMP-gated sensory channel subunit TAX-2. TAX-2 acts in several sensory neurons that are exposed to body fluid to generate the aversive response through a motor network that underlies navigation. Osmotic upshifts activate the body cavity sensory neuron URX, which is known to induce aversion upon activation. Together, our results characterize the molecular and cellular mechanisms underlying a novel sensorimotor response to osmotic stimuli and reveal that C. elegans engages different behaviors and the underlying mechanisms to regulate responses to extracellular osmolarity. PMID:28451641

Modality of fear cues affects acoustic startle potentiation but not heart-rate response in patients with dental phobia

PubMed Central

Wannemüller, André; Sartory, Gudrun; Elsesser, Karin; Lohrmann, Thomas; Jöhren, Hans P.

2015-01-01

The acoustic startle response (SR) has consistently been shown to be enhanced by fear-arousing cross-modal background stimuli in phobics. Intra-modal fear-potentiation of acoustic SR was rarely investigated and generated inconsistent results. The present study compared the acoustic SR to phobia-related sounds with that to phobia-related pictures in 104 dental phobic patients and 22 controls. Acoustic background stimuli were dental treatment noises and birdsong and visual stimuli were dental treatment and neutral control pictures. Background stimuli were presented for 4 s, randomly followed by the administration of the startle stimulus. In addition to SR, heart-rate (HR) was recorded throughout the trials. Irrespective of their content, background pictures elicited greater SR than noises in both groups with a trend for phobic participants to show startle potentiation to phobia-related pictures but not noises. Unlike controls, phobics showed HR acceleration to both dental pictures and noises. HR acceleration of the phobia group was significantly positively correlated with SR in the noise condition only. The acoustic SR to phobia-related noises is likely to be inhibited by prolonged sensorimotor gating. PMID:25774142

Investigating the underlying mechanisms of aberrant behaviors in bipolar disorder from patients to models

PubMed Central

van Enkhuizen, Jordy; Geyer, Mark A.; Minassian, Arpi; Perry, William; Henry, Brook L.; Young, Jared W.

2015-01-01

Psychiatric patients with bipolar disorder suffer from states of depression and mania, during which a variety of symptoms are present. Current treatments are limited and neurocognitive deficits in particular often remain untreated. Targeted therapies based on the biological mechanisms of bipolar disorder could fill this gap and benefit patients and their families. Developing targeted therapies would benefit from appropriate animal models which are challenging to establish, but remain a vital tool. In this review, we summarize approaches to create a valid model relevant to bipolar disorder. We focus on studies that use translational tests of multivariate exploratory behavior, sensorimotor gating, decision-making under risk, and attentional functioning to discover profiles that are consistent between patients and rodent models. Using this battery of translational tests, similar behavior profiles in bipolar mania patients and mice with reduced dopamine transporter activity have been identified. Future investigations should combine other animal models that are biologically relevant to the neuropsychiatric disorder with translational behavioral assessment as outlined here. This methodology can be utilized to develop novel targeted therapies that relieve symptoms for more patients without common side effects caused by current treatments. PMID:26297513

Prenatal NMDA Receptor Antagonism Impaired Proliferation of Neuronal Progenitor, Leading to Fewer Glutamatergic Neurons in the Prefrontal Cortex

PubMed Central

Toriumi, Kazuya; Mouri, Akihiro; Narusawa, Shiho; Aoyama, Yuki; Ikawa, Natsumi; Lu, Lingling; Nagai, Taku; Mamiya, Takayoshi; Kim, Hyoung-Chun; Nabeshima, Toshitaka

2012-01-01

N-methyl--aspartate (NMDA) receptor is a glutamate receptor which has an important role on mammalian brain development. We have reported that prenatal treatment with phencyclidine (PCP), a NMDA receptor antagonist, induces long-lasting behavioral deficits and neurochemical changes. However, the mechanism by which the prenatal antagonism of NMDA receptor affects neurodevelopment, resulting in behavioral deficits, has remained unclear. Here, we report that prenatal NMDA receptor antagonism impaired the proliferation of neuronal progenitors, leading to a decrease in the progenitor pool in the ventricular and the subventricular zone. Furthermore, using a PCR array focused on neurogenesis and neuronal stem cells, we evaluated changes in gene expression causing the impairment of neuronal progenitor proliferation and found aberrant gene expression, such as Notch2 and Ntn1, in prenatal PCP-treated mice. Consequently, the density of glutamatergic neurons in the prefrontal cortex was decreased, probably resulting in glutamatergic hypofunction. Prenatal PCP-treated mice displayed behavioral deficits in cognitive memory and sensorimotor gating until adulthood. These findings suggest that NMDA receptors regulate the proliferation and maturation of progenitor cells for glutamatergic neuron during neurodevelopment, probably via the regulation of gene expression. PMID:22257896

Effects of Olanzapine, Risperidone and Haloperidol on Prepulse Inhibition in Schizophrenia Patients: A Double-Blind, Randomized Controlled Trial

PubMed Central

Wynn, Jonathan K.; Green, Michael F.; Sprock, Joyce; Light, Gregory A.; Widmark, Clifford; Reist, Christopher; Erhart, Stephen; Marder, Stephen R.; Mintz, Jim; Braff, David L.

2009-01-01

Prepulse inhibition (PPI), whereby the startle eyeblink response is inhibited by a relatively weak non-startling stimulus preceding the powerful startle eliciting stimulus, is a measure of sensorimotor gating and has been shown to be deficient in schizophrenia patients. There is considerable interest in whether conventional and/or atypical antipsychotic medications can “normalize” PPI deficits in schizophrenia patients. 51 schizophrenia patients participated in a randomized, double-blind controlled trial on the effects of three commonly-prescribed antipsychotic medications (risperidone, olanzapine, or haloperidol) on PPI, startle habituation, and startle reactivity. Patients were tested at baseline, Week 4 and Week 8. Mixed model regression analyses revealed that olanzapine significantly improved PPI from Week 4 to Week 8, and that at Week 8 patients receiving olanzapine produced significantly greater PPI than those receiving risperidone, but not haloperidol. There were no effects of medication on startle habituation or startle reactivity. These results support the conclusion that olanzapine effectively increased PPI in schizophrenia patients, but that risperidone and haloperidol had no such effects. The results are discussed in terms of animal models, neural substrates, and treatment implications. PMID:17662577

Cannabinoids and Vanilloids in Schizophrenia: Neurophysiological Evidence and Directions for Basic Research.

PubMed

Ruggiero, Rafael N; Rossignoli, Matheus T; De Ross, Jana B; Hallak, Jaime E C; Leite, Joao P; Bueno-Junior, Lezio S

2017-01-01

Much of our knowledge of the endocannabinoid system in schizophrenia comes from behavioral measures in rodents, like prepulse inhibition of the acoustic startle and open-field locomotion, which are commonly used along with neurochemical approaches or drug challenge designs. Such methods continue to map fundamental mechanisms of sensorimotor gating, hyperlocomotion, social interaction, and underlying monoaminergic, glutamatergic, and GABAergic disturbances. These strategies will require, however, a greater use of neurophysiological tools to better inform clinical research. In this sense, electrophysiology and viral vector-based circuit dissection, like optogenetics, can further elucidate how exogenous cannabinoids worsen (e.g., tetrahydrocannabinol, THC) or ameliorate (e.g., cannabidiol, CBD) schizophrenia symptoms, like hallucinations, delusions, and cognitive deficits. Also, recent studies point to a complex endocannabinoid-endovanilloid interplay, including the influence of anandamide (endogenous CB 1 and TRPV 1 agonist) on cognitive variables, such as aversive memory extinction. In fact, growing interest has been devoted to TRPV 1 receptors as promising therapeutic targets. Here, these issues are reviewed with an emphasis on the neurophysiological evidence. First, we contextualize imaging and electrographic findings in humans. Then, we present a comprehensive review on rodent electrophysiology. Finally, we discuss how basic research will benefit from further combining psychopharmacological and neurophysiological tools.

No Neuromuscular Side-Effects of Scopolamine in Sensorimotor Control and Force-Generating Capacity Among Parabolic Fliers

NASA Astrophysics Data System (ADS)

Ritzmann, Ramona; Freyler, Kathrin; Krause, Anne; Gollhofer, Albert

2016-10-01

Scopolamine is used to counteract motion sickness in parabolic flight (PF) experiments. Although the drug's anticholinergic properties effectively impede vomiting, recent studies document other sensory side-effects in the central nervous system that may considerably influence sensorimotor performance. This study aimed to quantify such effects in order to determine if they are of methodological and operational significance for sensorimotor control. Ten subjects of a PF campaign received a weight-sex-based dose of a subcutaneous scopolamine injection. Sensorimotor performance was recorded before medication, 20min, 2h and 4h after injection in four space-relevant paradigms: balance control in one-leg stance with eyes open (protocol 1) and closed as well as force-generating capacity in countermovement jumps and hops (protocol 2). Postural sway, forces and joint angles were recorded. Neuromuscular control was assessed by electromyography and peripheral nerve stimulation; H-reflexes and M-waves were used to monitor spinal excitability of the Ia afferent reflex circuitry and maximal motor output. (1) H-reflex amplitudes, latencies and functional reflexes remained unchanged after scopolamine injection. (2) M-waves, neuromuscular activation intensities and antagonistic muscle coordination did not change with scopolamine administration. (3) Balance performance and force-generating capacity were not impeded by scopolamine. We found no evidence for changes in sensorimotor control in response to scopolamine injection. Sensory processing of daily relevant reflexes, spinal excitability, maximal motor output and performance parameters were not sensitive to the medication. We conclude that scopolamine administration can be used to counteract motion sickness in PF without methodological and operational concerns or interference regarding sensorimotor skills associated with neuromuscular control.

Upper extremity sensorimotor control among collegiate football players.

PubMed

Laudner, Kevin G

2012-03-01

Injuries stemming from shoulder instability are very common among athletes participating in contact sports, such as football. Previous research has shown that increased laxity negatively affects the function of the sensorimotor system potentially leading to a pathological cycle of shoulder dysfunction. Currently, there are no data detailing such effects among football players. Therefore, the purpose of this study was to examine the differences in upper extremity sensorimotor control among football players compared with that of a control group. Forty-five collegiate football players and 70 male control subjects with no previous experience in contact sports participated. All the subjects had no recent history of upper extremity injury. Each subject performed three 30-second upper extremity balance trials on each arm. The balance trials were conducted in a single-arm push-up position with the test arm in the center of a force platform and the subjects' feet on a labile device. The trials were averaged, and the differences in radial area deviation between groups were analyzed using separate 1-way analyses of variance (p < 0.05). The football players showed significantly more radial area deviation of the dominant (0.41 ± 1.23 cm2, p = 0.02) and nondominant arms (0.47 ± 1.63 cm2, p = 0.03) when compared with the control group. These results suggest that football players may have decreased sensorimotor control of the upper extremity compared with individuals with no contact sport experience. The decreased upper extremity sensorimotor control among the football players may be because of the frequent impacts accumulated during football participation. Football players may benefit from exercises that target the sensorimotor system. These findings may also be beneficial in the evaluation and treatment of various upper extremity injuries among football players.

Cortical presynaptic control of dorsal horn C-afferents in the rat.

PubMed

Moreno-López, Yunuen; Pérez-Sánchez, Jimena; Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Rojas-Piloni, Gerardo

2013-01-01

Lamina 5 sensorimotor cortex pyramidal neurons project to the spinal cord, participating in the modulation of several modalities of information transmission. A well-studied mechanism by which the corticospinal projection modulates sensory information is primary afferent depolarization, which has been characterized in fast muscular and cutaneous, but not in slow-conducting nociceptive skin afferents. Here we investigated whether the inhibition of nociceptive sensory information, produced by activation of the sensorimotor cortex, involves a direct presynaptic modulation of C primary afferents. In anaesthetized male Wistar rats, we analyzed the effects of sensorimotor cortex activation on post tetanic potentiation (PTP) and the paired pulse ratio (PPR) of dorsal horn field potentials evoked by C-fiber stimulation in the sural (SU) and sciatic (SC) nerves. We also explored the time course of the excitability changes in nociceptive afferents produced by cortical stimulation. We observed that the development of PTP was completely blocked when C-fiber tetanic stimulation was paired with cortex stimulation. In addition, sensorimotor cortex activation by topical administration of bicuculline (BIC) produced a reduction in the amplitude of C-fiber responses, as well as an increase in the PPR. Furthermore, increases in the intraspinal excitability of slow-conducting fiber terminals, produced by sensorimotor cortex stimulation, were indicative of primary afferent depolarization. Topical administration of BIC in the spinal cord blocked the inhibition of C-fiber neuronal responses produced by cortical stimulation. Dorsal horn neurons responding to sensorimotor cortex stimulation also exhibited a peripheral receptive field and responded to stimulation of fast cutaneous myelinated fibers. Our results suggest that corticospinal inhibition of nociceptive responses is due in part to a modulation of the excitability of primary C-fibers by means of GABAergic inhibitory interneurons.

Cortical Presynaptic Control of Dorsal Horn C–Afferents in the Rat

PubMed Central

Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Rojas-Piloni, Gerardo

2013-01-01

Lamina 5 sensorimotor cortex pyramidal neurons project to the spinal cord, participating in the modulation of several modalities of information transmission. A well-studied mechanism by which the corticospinal projection modulates sensory information is primary afferent depolarization, which has been characterized in fast muscular and cutaneous, but not in slow-conducting nociceptive skin afferents. Here we investigated whether the inhibition of nociceptive sensory information, produced by activation of the sensorimotor cortex, involves a direct presynaptic modulation of C primary afferents. In anaesthetized male Wistar rats, we analyzed the effects of sensorimotor cortex activation on post tetanic potentiation (PTP) and the paired pulse ratio (PPR) of dorsal horn field potentials evoked by C–fiber stimulation in the sural (SU) and sciatic (SC) nerves. We also explored the time course of the excitability changes in nociceptive afferents produced by cortical stimulation. We observed that the development of PTP was completely blocked when C-fiber tetanic stimulation was paired with cortex stimulation. In addition, sensorimotor cortex activation by topical administration of bicuculline (BIC) produced a reduction in the amplitude of C–fiber responses, as well as an increase in the PPR. Furthermore, increases in the intraspinal excitability of slow-conducting fiber terminals, produced by sensorimotor cortex stimulation, were indicative of primary afferent depolarization. Topical administration of BIC in the spinal cord blocked the inhibition of C–fiber neuronal responses produced by cortical stimulation. Dorsal horn neurons responding to sensorimotor cortex stimulation also exhibited a peripheral receptive field and responded to stimulation of fast cutaneous myelinated fibers. Our results suggest that corticospinal inhibition of nociceptive responses is due in part to a modulation of the excitability of primary C–fibers by means of GABAergic inhibitory interneurons. PMID:23935924

How the impact of median neuropathy on sensorimotor control capability of hands for diabetes: an achievable assessment from functional perspectives.

PubMed

Chiu, Haw-Yen; Hsu, Hsiu-Yun; Kuo, Li-Chieh; Su, Fong-Chin; Yu, Hui-I; Hua, Shih-Che; Lu, Chieh-Hsiang

2014-01-01

To comprehend the sensorimotor control ability in diabetic hands, this study investigated the sensation, motor function and precision pinch performances derived from a pinch-holding-up activity (PHUA) test of the hands of diabetic patients and healthy subjects. The precision, sensitivity and specificity of the PHUA test in the measurements of diabetic patients were also analyzed. We hypothesized that the diabetic hands would have impacts on the sensorimotor functions of the hand performances under functionally quantitative measurements. One hundred and fifty-nine patients with clinically defined diabetes mellitus (DM) and 95 age- and gender-matched healthy controls were included. Semmes-Weinstein monofilament (SWM), static and moving two-point discrimination (S2PD and M2PD), maximal pinch strength and precision pinch performance tests were conducted to evaluate the sensation, motor and sensorimotor status of the recruited hands. The results showed that there were significant differences (all p<0.05) in SWM, S2PD, M2PD and maximum pinch strength between the DM and control groups. A higher force ratio in the DM patients than in the controls (p<0.001) revealed a poor ability of pinch force adjustment in the DM patients. The percentage of maximal pinch strength was also significantly different (p<0.001) between the DM and control groups. The sensitivity, specificity and area under the receiver operating characteristic curve were 0.85, 0.51, and 0.724, respectively, for the PHUA test. Statistically significant degradations in sensory and motor functions and sensorimotor control ability were observed in the hands of the diabetic patients. The PHUA test could be feasibly used as a clinical tool to determine the sensorimotor function of the hands of diabetic patients from a functional perspective.

Integration of Gravitational Torques in Cerebellar Pathways Allows for the Dynamic Inverse Computation of Vertical Pointing Movements of a Robot Arm

PubMed Central

Gentili, Rodolphe J.; Papaxanthis, Charalambos; Ebadzadeh, Mehdi; Eskiizmirliler, Selim; Ouanezar, Sofiane; Darlot, Christian

2009-01-01

Background Several authors suggested that gravitational forces are centrally represented in the brain for planning, control and sensorimotor predictions of movements. Furthermore, some studies proposed that the cerebellum computes the inverse dynamics (internal inverse model) whereas others suggested that it computes sensorimotor predictions (internal forward model). Methodology/Principal Findings This study proposes a model of cerebellar pathways deduced from both biological and physical constraints. The model learns the dynamic inverse computation of the effect of gravitational torques from its sensorimotor predictions without calculating an explicit inverse computation. By using supervised learning, this model learns to control an anthropomorphic robot arm actuated by two antagonists McKibben artificial muscles. This was achieved by using internal parallel feedback loops containing neural networks which anticipate the sensorimotor consequences of the neural commands. The artificial neural networks architecture was similar to the large-scale connectivity of the cerebellar cortex. Movements in the sagittal plane were performed during three sessions combining different initial positions, amplitudes and directions of movements to vary the effects of the gravitational torques applied to the robotic arm. The results show that this model acquired an internal representation of the gravitational effects during vertical arm pointing movements. Conclusions/Significance This is consistent with the proposal that the cerebellar cortex contains an internal representation of gravitational torques which is encoded through a learning process. Furthermore, this model suggests that the cerebellum performs the inverse dynamics computation based on sensorimotor predictions. This highlights the importance of sensorimotor predictions of gravitational torques acting on upper limb movements performed in the gravitational field. PMID:19384420

How the Impact of Median Neuropathy on Sensorimotor Control Capability of Hands for Diabetes: An Achievable Assessment from Functional Perspectives

PubMed Central

Chiu, Haw-Yen; Hsu, Hsiu-Yun; Kuo, Li-Chieh; Su, Fong-Chin; Yu, Hui-I; Hua, Shih-Che; Lu, Chieh-Hsiang

2014-01-01

To comprehend the sensorimotor control ability in diabetic hands, this study investigated the sensation, motor function and precision pinch performances derived from a pinch-holding-up activity (PHUA) test of the hands of diabetic patients and healthy subjects. The precision, sensitivity and specificity of the PHUA test in the measurements of diabetic patients were also analyzed. We hypothesized that the diabetic hands would have impacts on the sensorimotor functions of the hand performances under functionally quantitative measurements. One hundred and fifty-nine patients with clinically defined diabetes mellitus (DM) and 95 age- and gender-matched healthy controls were included. Semmes-Weinstein monofilament (SWM), static and moving two-point discrimination (S2PD and M2PD), maximal pinch strength and precision pinch performance tests were conducted to evaluate the sensation, motor and sensorimotor status of the recruited hands. The results showed that there were significant differences (all p<0.05) in SWM, S2PD, M2PD and maximum pinch strength between the DM and control groups. A higher force ratio in the DM patients than in the controls (p<0.001) revealed a poor ability of pinch force adjustment in the DM patients. The percentage of maximal pinch strength was also significantly different (p<0.001) between the DM and control groups. The sensitivity, specificity and area under the receiver operating characteristic curve were 0.85, 0.51, and 0.724, respectively, for the PHUA test. Statistically significant degradations in sensory and motor functions and sensorimotor control ability were observed in the hands of the diabetic patients. The PHUA test could be feasibly used as a clinical tool to determine the sensorimotor function of the hands of diabetic patients from a functional perspective. PMID:24722361

Stinger Post Hybrid Simulation: Design Description and Users’ Manual

DTIC Science & Technology

1983-04-01

function of three variables. Table 4 MVFG Modes £ ?*" Mode Function Number Argument Number Trunking Station Address Output Hole Argument...between JA and J7. This permits the signal to control a normally-open, single-throw minature relay. It closes the remote operate line when a logic...logic functions are also performed on the card. A normally- open, single-throw minature relay (U5) and an AND gate (1/4 of Ul) are used to perform the

Body Constraints on Motor Simulation in Autism Spectrum Disorders

ERIC Educational Resources Information Center

Conson, Massimiliano; Hamilton, Antonia; De Bellis, Francesco; Errico, Domenico; Improta, Ilaria; Mazzarella, Elisabetta; Trojano, Luigi; Frolli, Alessandro

2016-01-01

Developmental data suggested that mental simulation skills become progressively dissociated from overt motor activity across development. Thus, efficient simulation is rather independent from current sensorimotor information. Here, we tested the impact of bodily (sensorimotor) information on simulation skills of adolescents with Autism Spectrum…

Frontal plane hip and ankle sensorimotor function, not age, predicts unipedal stance time

PubMed Central

Allet, Lara; Kim, Hogene; Ashton-Miller, James; De Mott, Trina; Richardson, James K.

2011-01-01

Introduction Changes occur in muscles and nerves with aging. This study aimed to explore the relationship between unipedal stance time (UST) and frontal plane hip and ankle sensorimotor function in subjects with diabetic neuropathy. Methods UST, quantitative measures of frontal plane ankle proprioceptive thresholds, and ankle and hip motor function were tested in forty-one persons with a spectrum of lower limb sensorimotor function, ranging from healthy to moderately severe diabetic neuropathy. Results Frontal plane hip and ankle sensorimotor function demonstrated significant relationships with UST. Multivariate analysis identified only composite hip strength, composite ankle proprioceptive threshold, and age to be significant predictors of UST (R2=0.73); they explained 46%, 24% and 3% of the variance, respectively. Discussion/Conclusions Frontal plane hip strength was the single best predictor of UST and appeared to compensate for less precise ankle proprioceptive thresholds. This finding is clinically relevant given the possibility of strengthening the hip, even in patients with significant PN. . PMID:22431092

Predicting future learning from baseline network architecture.

PubMed

Mattar, Marcelo G; Wymbs, Nicholas F; Bock, Andrew S; Aguirre, Geoffrey K; Grafton, Scott T; Bassett, Danielle S

2018-05-15

Human behavior and cognition result from a complex pattern of interactions between brain regions. The flexible reconfiguration of these patterns enables behavioral adaptation, such as the acquisition of a new motor skill. Yet, the degree to which these reconfigurations depend on the brain's baseline sensorimotor integration is far from understood. Here, we asked whether spontaneous fluctuations in sensorimotor networks at baseline were predictive of individual differences in future learning. We analyzed functional MRI data from 19 participants prior to six weeks of training on a new motor skill. We found that visual-motor connectivity was inversely related to learning rate: sensorimotor autonomy at baseline corresponded to faster learning in the future. Using three additional scans, we found that visual-motor connectivity at baseline is a relatively stable individual trait. These results suggest that individual differences in motor skill learning can be predicted from sensorimotor autonomy at baseline prior to task execution. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Dissecting Driver Behaviors Under Cognitive, Emotional, Sensorimotor, and Mixed Stressors

PubMed Central

Pavlidis, I.; Dcosta, M.; Taamneh, S.; Manser, M.; Ferris, T.; Wunderlich, R.; Akleman, E.; Tsiamyrtzis, P.

2016-01-01

In a simulation experiment we studied the effects of cognitive, emotional, sensorimotor, and mixed stressors on driver arousal and performance with respect to (wrt) baseline. In a sample of n = 59 drivers, balanced in terms of age and gender, we found that all stressors incurred significant increases in mean sympathetic arousal accompanied by significant increases in mean absolute steering. The latter, translated to significantly larger range of lane departures only in the case of sensorimotor and mixed stressors, indicating more dangerous driving wrt baseline. In the case of cognitive or emotional stressors, often a smaller range of lane departures was observed, indicating safer driving wrt baseline. This paradox suggests an effective coping mechanism at work, which compensates erroneous reactions precipitated by cognitive or emotional conflict. This mechanisms’ grip slips, however, when the feedback loop is intermittently severed by sensorimotor distractions. Interestingly, mixed stressors did not affect crash rates in startling events, suggesting that the coping mechanism’s compensation time scale is above the range of neurophysiological latency. PMID:27170291

Sensorimotor Learning during a Marksmanship Task in Immersive Virtual Reality

PubMed Central

Rao, Hrishikesh M.; Khanna, Rajan; Zielinski, David J.; Lu, Yvonne; Clements, Jillian M.; Potter, Nicholas D.; Sommer, Marc A.; Kopper, Regis; Appelbaum, Lawrence G.

2018-01-01

Sensorimotor learning refers to improvements that occur through practice in the performance of sensory-guided motor behaviors. Leveraging novel technical capabilities of an immersive virtual environment, we probed the component kinematic processes that mediate sensorimotor learning. Twenty naïve subjects performed a simulated marksmanship task modeled after Olympic Trap Shooting standards. We measured movement kinematics and shooting performance as participants practiced 350 trials while receiving trial-by-trial feedback about shooting success. Spatiotemporal analysis of motion tracking elucidated the ballistic and refinement phases of hand movements. We found systematic changes in movement kinematics that accompanied improvements in shot accuracy during training, though reaction and response times did not change over blocks. In particular, we observed longer, slower, and more precise ballistic movements that replaced effort spent on corrections and refinement. Collectively, these results leverage developments in immersive virtual reality technology to quantify and compare the kinematics of movement during early learning of full-body sensorimotor orienting. PMID:29467693

Frontal plane hip and ankle sensorimotor function, not age, predicts unipedal stance time.

PubMed

Allet, Lara; Kim, Hogene; Ashton-Miller, James; De Mott, Trina; Richardson, James K

2012-04-01

Changes occur in muscles and nerves with aging. In this study we explore the relationship between unipedal stance time (UST) and frontal plane hip and ankle sensorimotor function in subjects with diabetic neuropathy. UST, quantitative measures of frontal plane ankle proprioceptive thresholds, and ankle and hip motor function were tested in 41 subjects with a spectrum of lower limb sensorimotor function ranging from healthy to moderately severe diabetic neuropathy. Frontal plane hip and ankle sensorimotor function demonstrated significant relationships with UST. Multivariate analysis identified only composite hip strength, ankle proprioceptive threshold, and age to be significant predictors of UST (R(2) = 0.73), explaining 46%, 24%, and 3% of the variance, respectively. Frontal plane hip strength was the single best predictor of UST and appeared to compensate for less precise ankle proprioceptive thresholds. This finding is clinically relevant given the possibility of strengthening the hip, even in patients with significant peripheral neuropathy. Copyright © 2011 Wiley Periodicals, Inc.

Dissecting Driver Behaviors Under Cognitive, Emotional, Sensorimotor, and Mixed Stressors.

PubMed

Pavlidis, I; Dcosta, M; Taamneh, S; Manser, M; Ferris, T; Wunderlich, R; Akleman, E; Tsiamyrtzis, P

2016-05-12

In a simulation experiment we studied the effects of cognitive, emotional, sensorimotor, and mixed stressors on driver arousal and performance with respect to (wrt) baseline. In a sample of n = 59 drivers, balanced in terms of age and gender, we found that all stressors incurred significant increases in mean sympathetic arousal accompanied by significant increases in mean absolute steering. The latter, translated to significantly larger range of lane departures only in the case of sensorimotor and mixed stressors, indicating more dangerous driving wrt baseline. In the case of cognitive or emotional stressors, often a smaller range of lane departures was observed, indicating safer driving wrt baseline. This paradox suggests an effective coping mechanism at work, which compensates erroneous reactions precipitated by cognitive or emotional conflict. This mechanisms' grip slips, however, when the feedback loop is intermittently severed by sensorimotor distractions. Interestingly, mixed stressors did not affect crash rates in startling events, suggesting that the coping mechanism's compensation time scale is above the range of neurophysiological latency.

A Low-Cost, Open-Source, Compliant Hand for Enabling Sensorimotor Control for People with Transradial Amputations

PubMed Central

Akhtar, Aadeel; Choi, Kyung Yun; Fatina, Michael; Cornman, Jesse; Wu, Edward; Sombeck, Joseph; Yim, Chris; Slade, Patrick; Lee, Jason; Moore, Jack; Gonzales, Daniel; Wu, Alvin; Anderson, Garrett; Rotter, David; Shin, Cliff; Bretl, Timothy

2017-01-01

In this paper, we describe the design and implementation of a low-cost, open-source prosthetic hand that enables both motor control and sensory feedback for people with transradial amputations. We integrate electromyographic pattern recognition for motor control along with contact reflexes and sensory substitution to provide feedback to the user. Compliant joints allow for robustness to impacts. The entire hand can be built for around $550. This low cost makes research and development of sensorimotor prosthetic hands more accessible to researchers worldwide, while also being affordable for people with amputations in developing nations. We evaluate the sensorimotor capabilites of our hand with a subject with a transradial amputation. We show that using contact reflexes and sensory substitution, when compared to standard myoelectric prostheses that lack these features, improves grasping of delicate objects like an eggshell and a cup of water both with and without visual feedback. Our hand is easily integrated into standard sockets, facilitating long-term testing of sensorimotor capabilities. PMID:28261008

Parallel, but Dissociable, Processing in Discrete Corticostriatal Inputs Encodes Skill Learning.

PubMed

Kupferschmidt, David A; Juczewski, Konrad; Cui, Guohong; Johnson, Kari A; Lovinger, David M

2017-10-11

Changes in cortical and striatal function underlie the transition from novel actions to refined motor skills. How discrete, anatomically defined corticostriatal projections function in vivo to encode skill learning remains unclear. Using novel fiber photometry approaches to assess real-time activity of associative inputs from medial prefrontal cortex to dorsomedial striatum and sensorimotor inputs from motor cortex to dorsolateral striatum, we show that associative and sensorimotor inputs co-engage early in action learning and disengage in a dissociable manner as actions are refined. Disengagement of associative, but not sensorimotor, inputs predicts individual differences in subsequent skill learning. Divergent somatic and presynaptic engagement in both projections during early action learning suggests potential learning-related in vivo modulation of presynaptic corticostriatal function. These findings reveal parallel processing within associative and sensorimotor circuits that challenges and refines existing views of corticostriatal function and expose neuronal projection- and compartment-specific activity dynamics that encode and predict action learning. Published by Elsevier Inc.

Thalamo-Sensorimotor Functional Connectivity Correlates with World Ranking of Olympic, Elite, and High Performance Athletes.

PubMed

Huang, Zirui; Davis, Henry Hap; Wolff, Annemarie; Northoff, Georg

2017-01-01

Brain plasticity studies have shown functional reorganization in participants with outstanding motor expertise. Little is known about neural plasticity associated with exceptionally long motor training or of its predictive value for motor performance excellence. The present study utilised resting-state functional magnetic resonance imaging (rs-fMRI) in a unique sample of world-class athletes: Olympic, elite, and internationally ranked swimmers ( n = 30). Their world ranking ranged from 1st to 250th: each had prepared for participation in the Olympic Games. Combining rs-fMRI graph-theoretical and seed-based functional connectivity analyses, it was discovered that the thalamus has its strongest connections with the sensorimotor network in elite swimmers with the highest world rankings (career best rank: 1-35). Strikingly, thalamo-sensorimotor functional connections were highly correlated with the swimmers' motor performance excellence, that is, accounting for 41% of the individual variance in best world ranking. Our findings shed light on neural correlates of long-term athletic performance involving thalamo-sensorimotor functional circuits.

Assessment and rehabilitation of central sensory impairments for balance in mTBI using auditory biofeedback: a randomized clinical trial.

PubMed

Fino, Peter C; Peterka, Robert J; Hullar, Timothy E; Murchison, Chad; Horak, Fay B; Chesnutt, James C; King, Laurie A

2017-02-23

Complaints of imbalance are common non-resolving signs in individuals with post-concussive syndrome. Yet, there is no consensus rehabilitation for non-resolving balance complaints following mild traumatic brain injury (mTBI). The heterogeneity of balance deficits and varied rates of recovery suggest varied etiologies and a need for interventions that address the underlying causes of poor balance function. Our central hypothesis is that most chronic balance deficits after mTBI result from impairments in central sensorimotor integration that may be helped by rehabilitation. Two studies are described to 1) characterize balance deficits in people with mTBI who have chronic, non-resolving balance deficits compared to healthy control subjects, and 2) determine the efficacy of an augmented vestibular rehabilitation program using auditory biofeedback to improve central sensorimotor integration, static and dynamic balance, and functional activity in patients with chronic mTBI. Two studies are described. Study 1 is a cross-sectional study to take place jointly at Oregon Health and Science University and the VA Portland Health Care System. The study participants will be individuals with non-resolving complaints of balance following mTBI and age- and gender-matched controls who meet all inclusion criteria. The primary outcome will be measures of central sensorimotor integration derived from a novel central sensorimotor integration test. Study 2 is a randomized controlled intervention to take place at Oregon Health & Science University. In this study, participants from Study 1 with mTBI and abnormal central sensorimotor integration will be randomized into two rehabilitation interventions. The interventions will be 6 weeks of vestibular rehabilitation 1) with or 2) without the use of an auditory biofeedback device. The primary outcome measure is the daily activity of the participants measured using an inertial sensor. The results of these two studies will improve our understanding of the nature of balance deficits in people with mTBI by providing quantitative metrics of central sensorimotor integration, balance, and vestibular and ocular motor function. Study 2 will examine the potential for augmented rehabilitation interventions to improve central sensorimotor integration. This trial is registered at clinicaltrials.gov ( NCT02748109 ).

From sensorimotor learning to memory cells in prefrontal and temporal association cortex: a neurocomputational study of disembodiment.

PubMed

Pulvermüller, Friedemann; Garagnani, Max

2014-08-01

Memory cells, the ultimate neurobiological substrates of working memory, remain active for several seconds and are most commonly found in prefrontal cortex and higher multisensory areas. However, if correlated activity in "embodied" sensorimotor systems underlies the formation of memory traces, why should memory cells emerge in areas distant from their antecedent activations in sensorimotor areas, thus leading to "disembodiment" (movement away from sensorimotor systems) of memory mechanisms? We modelled the formation of memory circuits in six-area neurocomputational architectures, implementing motor and sensory primary, secondary and higher association areas in frontotemporal cortices along with known between-area neuroanatomical connections. Sensorimotor learning driven by Hebbian neuroplasticity led to formation of cell assemblies distributed across the different areas of the network. These action-perception circuits (APCs) ignited fully when stimulated, thus providing a neural basis for long-term memory (LTM) of sensorimotor information linked by learning. Subsequent to ignition, activity vanished rapidly from APC neurons in sensorimotor areas but persisted in those in multimodal prefrontal and temporal areas. Such persistent activity provides a mechanism for working memory for actions, perceptions and symbols, including short-term phonological and semantic storage. Cell assembly ignition and "disembodied" working memory retreat of activity to multimodal areas are documented in the neurocomputational models' activity dynamics, at the level of single cells, circuits, and cortical areas. Memory disembodiment is explained neuromechanistically by APC formation and structural neuroanatomical features of the model networks, especially the central role of multimodal prefrontal and temporal cortices in bridging between sensory and motor areas. These simulations answer the "where" question of cortical working memory in terms of distributed APCs and their inner structure, which is, in part, determined by neuroanatomical structure. As the neurocomputational model provides a mechanistic explanation of how memory-related "disembodied" neuronal activity emerges in "embodied" APCs, it may be key to solving aspects of the embodiment debate and eventually to a better understanding of cognitive brain functions. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.