Lies, Barbara; Beck, Katharina; Keppler, Jonas; Saur, Dieter; Groneberg, Dieter; Friebe, Andreas
In the enteric nervous systems, NO is released from nitrergic neurons as a major inhibitory neurotransmitter. NO acts via NO-sensitive guanylyl cyclase (NO-GC), which is found in different gastrointestinal (GI) cell types including smooth muscle cells (SMCs) and interstitial cells of Cajal (ICC). The precise mechanism of nitrergic signalling through these two cell types to regulate colonic spontaneous contractions is not fully understood yet. In the present study we investigated the impact of endogenous and exogenous NO on colonic contractile motor activity using mice lacking nitric oxide-sensitive guanylyl cyclase (NO-GC) globally and specifically in SMCs and ICC. Longitudinal smooth muscle of proximal colon from wild-type (WT) and knockout (KO) mouse strains exhibited spontaneous contractile activity ex vivo. WT and smooth muscle-specific guanylyl cyclase knockout (SMC-GCKO) colon showed an arrhythmic contractile activity with varying amplitudes and frequencies. In contrast, colon from global and ICC-specific guanylyl cyclase knockout (ICC-GCKO) animals showed a regular contractile rhythm with constant duration and amplitude of the rhythmic contractions. Nerve blockade (tetrodotoxin) or specific blockade of NO signalling (L-NAME, ODQ) did not significantly affect contractions of GCKO and ICC-GCKO colon whereas the arrhythmic contractile patterns of WT and SMC-GCKO colon were transformed into uniform motor patterns. In contrast, the response to electric field-stimulated neuronal NO release was similar in SMC-GCKO and global GCKO. In conclusion, our results indicate that basal enteric NO release acts via myenteric ICC to influence the generation of spontaneous contractions whereas the effects of elevated endogenous NO are mediated by SMCs in the murine proximal colon.
Sun, Jing; Zhang, Daohai; Bae, Dong-Hun; Sahni, Sumit; Jansson, Patric; Zheng, Ying; Zhao, Qian; Yue, Fei; Zheng, Minhua; Kovacevic, Zaklina; Richardson, Des R
The metastasis suppressor, N-myc downstream regulated gene 1 (NDRG1), is negatively correlated with tumor progression in multiple neoplasms, being a promising new target for cancer treatment. However, the precise molecular effects of NDRG1 remain unclear. Herein, we summarize recent advances in understanding the impact of NDRG1 on cancer metastasis with emphasis on its interactions with the key oncogenic nuclear factor-kappaB, phosphatidylinositol-3 kinase/phosphorylated AKT/mammalian target of rapamycin and Ras/Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling pathways. Recent studies demonstrating the inhibitory effects of NDRG1 on the epithelial-mesenchymal transition, a key initial step in metastasis, TGF-β pathway and the Wnt/β-catenin pathway are also described. Furthermore, NDRG1 was also demonstrated to regulate molecular motors in cancer cells, leading to inhibition of F-actin polymerization, stress fiber formation and subsequent reduction of cancer cell migration. Collectively, this review summarizes the underlying molecular mechanisms of the antimetastatic effects of NDRG1 in cancer cells.
Background Lower motor neurons in the spinal cord lose supraspinal inputs after complete spinal cord injury, leading to a loss of volitional control below the injury site. Extensive locomotor training with spinal cord stimulation can restore locomotion function after spinal cord injury in humans and animals. However, this locomotion is non-voluntary, meaning that subjects cannot control stimulation via their natural “intent”. A recent study demonstrated an advanced system that triggers a stimulator using forelimb stepping electromyographic patterns to restore quadrupedal walking in rats with spinal cord transection. However, this indirect source of “intent” may mean that other non-stepping forelimb activities may false-trigger the spinal stimulator and thus produce unwanted hindlimb movements. Methods We hypothesized that there are distinguishable neural activities in the primary motor cortex during treadmill walking, even after low-thoracic spinal transection in adult guinea pigs. We developed an electronic spinal bridge, called “Motolink”, which detects these neural patterns and triggers a “spinal” stimulator for hindlimb movement. This hardware can be head-mounted or carried in a backpack. Neural data were processed in real-time and transmitted to a computer for analysis by an embedded processor. Off-line neural spike analysis was conducted to calculate and preset the spike threshold for “Motolink” hardware. Results We identified correlated activities of primary motor cortex neurons during treadmill walking of guinea pigs with spinal cord transection. These neural activities were used to predict the kinematic states of the animals. The appropriate selection of spike threshold value enabled the “Motolink” system to detect the neural “intent” of walking, which triggered electrical stimulation of the spinal cord and induced stepping-like hindlimb movements. Conclusion We present a direct cortical “intent”-driven electronic spinal
Goertz, Richard Brandon; Wanat, Matthew J; Gomez, Jorge A; Brown, Zeliene J; Phillips, Paul E M; Paladini, Carlos A
Cocaine reinforcement is mediated by increased extracellular dopamine levels in the forebrain. This neurochemical effect was thought to require inhibition of dopamine reuptake, but cocaine is still reinforcing even in the absence of the dopamine transporter. Here, we demonstrate that the rapid elevation in dopamine levels and motor activity elicited by cocaine involves α1 receptor activation within the ventral midbrain. Activation of α1 receptors increases dopaminergic neuron burst firing by decreasing the calcium-activated potassium channel current (SK), as well as elevates dopaminergic neuron pacemaker firing through modulation of both SK and the hyperpolarization-activated cation currents (Ih). Furthermore, we found that cocaine increases both the pacemaker and burst-firing frequency of rat ventral-midbrain dopaminergic neurons through an α1 adrenergic receptor-dependent mechanism within the ventral tegmental area and substantia nigra pars compacta. These results demonstrate the mechanism underlying the critical role of α1 adrenergic receptors in the regulation of dopamine neurotransmission and behavior by cocaine.
Matsukawa, Kanji; Ishii, Kei; Kadowaki, Akito; Ishida, Tomoko; Idesako, Mitsuhiro; Liang, Nan
Our laboratory has suggested that central command provides selective inhibition of the cardiomotor component of aortic baroreflex at the start of exercise, preserving carotid sinus baroreflex. It is postulated that central command may modify the signal transduction of aortic baroreceptors, so as to decrease aortic baroreceptor input to the cardiovascular centers, and, thereby, can cause the selective inhibition of aortic baroreflex. To test the hypothesis, we directly analyzed the responses in multifiber aortic nerve activity (AoNA) and carotid sinus nerve activity (CsNA) during spontaneous motor activity in decerebrate, paralyzed cats. The increases of 62-104% in mean AoNA and CsNA were found during spontaneous motor activity, in proportion to a rise of 35 ± 3 mmHg (means ± SE) in mean arterial blood pressure (MAP), and had an attenuating tendency by restraining heart rate (HR) at the lower intrinsic frequency of 154 ± 6 beats/min. Brief occlusion of the abdominal aorta was conducted before and during spontaneous motor activity to produce a mechanically evoked increase in MAP and, thereby, to examine the stimulus-response relationship of arterial baroreceptors. Although the sensitivity of the MAP-HR baroreflex curve was markedly blunted during spontaneous motor activity, the stimulus-response relationships of AoNA and CsNA were not influenced by spontaneous motor activity, irrespective of the absence or presence of the HR restraint. Thus, it is concluded that aortic and carotid sinus baroreceptors can code beat-by-beat blood pressure during spontaneous motor activity in decerebrate cats and that central command is unlikely to modulate the signal transduction of arterial baroreceptors.
Schwarz, Peter B; Mir, Saba; Peever, John H
Noradrenergic neurotransmission in the brainstem is closely coupled to changes in muscle activity across the sleep-wake cycle, and noradrenaline is considered to be a key excitatory neuromodulator that reinforces the arousal-related stimulus on motoneurons to drive movement. However, it is unknown if α-1 noradrenoceptor activation increases motoneuron responsiveness to excitatory glutamate (AMPA) receptor-mediated inputs during natural behaviour. We studied the effects of noradrenaline on AMPA receptor-mediated motor activity at the motoneuron level in freely behaving rats, particularly during rapid eye movement (REM) sleep, a period during which both AMPA receptor-triggered muscle twitches and periods of muscle quiescence in which AMPA drive is silent are exhibited. Male rats were subjected to electromyography and electroencephalography recording to monitor sleep and waking behaviour. The implantation of a cannula into the trigeminal motor nucleus of the brainstem allowed us to perfuse noradrenergic and glutamatergic drugs by reverse microdialysis, and thus to use masseter muscle activity as an index of motoneuronal output. We found that endogenous excitation of both α-1 noradrenoceptor and AMPA receptors during waking are coupled to motor activity; however, REM sleep exhibits an absence of endogenous α-1 noradrenoceptor activity. Importantly, exogenous α-1 noradrenoceptor stimulation cannot reverse the muscle twitch suppression induced by AMPA receptor blockade and nor can it elevate muscle activity during quiet REM, a phase when endogenous AMPA receptor activity is subthreshold. We conclude that the presence of an endogenous glutamatergic drive is necessary for noradrenaline to trigger muscle activity at the level of the motoneuron in an animal behaving naturally.
Kasyan, I. I.; Kopanev, V. I.; Cherepakhin, M. A.; Yuganov, Y. M.
The material presented on the motor activity under weightless conditions (brief and long) leads to the conclusion that it is not significantly disrupted, if those being examined are secured at the workplaces. Some discoordination of movement, moderately expressed disruption of the precision of reproduction of assigned muscular forces, etc., were observed. Motor disorders decrease significantly in proportion to the length of stay under weightless conditions. This apparently takes place, as a consequence of formation of a new functional system, adequate to the conditions of weightlessness. Tests on intact and labyrinthectomized animals have demonstrated that signaling from the inner ear receptors is superfluous in weightlessness, since it promotes the onset of disruptions in the combined work of the position analyzers.
Beccano-Kelly, Dayne A; Volta, Mattia; Munsie, Lise N; Paschall, Sarah A; Tatarnikov, Igor; Co, Kimberley; Chou, Patrick; Cao, Li-Ping; Bergeron, Sabrina; Mitchell, Emma; Han, Heather; Melrose, Heather L; Tapia, Lucia; Raymond, Lynn A; Farrer, Matthew J; Milnerwood, Austen J
Mutations in leucine-rich repeat kinase 2 (Lrrk2) are the most common genetic cause of Parkinson's disease (PD), a neurodegenerative disorder affecting 1-2% of those >65 years old. The neurophysiology of LRRK2 remains largely elusive, although protein loss suggests a role in glutamatergic synapse transmission and overexpression studies show altered dopamine release in aged mice. We show that glutamate transmission is unaltered onto striatal projection neurons (SPNs) of adult LRRK2 knockout mice and that adult animals exhibit no detectable cognitive or motor deficits. Basal synaptic transmission is also unaltered in SPNs of LRRK2 overexpressing mice, but they do exhibit clear alterations to D2-receptor-mediated short-term synaptic plasticity, behavioral hypoactivity and impaired recognition memory. These phenomena are associated with decreased striatal dopamine tone and abnormal dopamine- and cAMP-regulated phosphoprotein 32 kDa signal integration. The data suggest that LRRK2 acts at the nexus of dopamine and glutamate signaling in the adult striatum, where it regulates dopamine levels, presynaptic glutamate release via D2-dependent synaptic plasticity and dopamine-receptor signal transduction.
Watanabe, Hidenori; Sato, Masa-aki; Suzuki, Takafumi; Nambu, Atsushi; Nishimura, Yukio; Kawato, Mitsuo; Isa, Tadashi
Subdural electrode arrays provide stable, less invasive electrocorticogram (ECoG) recordings of neural signals than multichannel needle electrodes. Accurate reconstruction of intracortical local field potentials (LFPs) from ECoG signals would provide a critical step for the development of a less invasive, high-performance brain-machine interface; however, neural signals from individual ECoG channels are generally coarse and have limitations in estimating deep layer LFPs. Here, we developed a high-density, 32-channel, micro-ECoG array and applied a sparse linear regression algorithm to reconstruct the LFPs at various depths of primary motor cortex (M1) in a monkey performing a reach-and-grasp task. At 0.2 mm beneath the cortical surface, the real and estimated LFPs were significantly correlated (correlation coefficient (r); 0.66 ± 0.11), and the r at 3.2 mm was still as high as 0.55 ± 0.04. A time-frequency analysis of the reconstructed LFP showed clear transition between resting and movements by the monkey. These methods would be a powerful tool with wide-ranging applicability in neuroscience studies.
Sabharwal, Priyanka; Lee, Changhee; Park, Sungjin; Rao, Meenakshi; Sockanathan, Shanthini
The specification of spinal interneuron and motor neuron identities initiates within progenitor cells, while motor neuron subtype diversification is regulated by hierarchical transcriptional programs implemented postmitotically. Here we find that mice lacking GDE2, a six-transmembrane protein that triggers motor neuron generation, exhibit selective losses of distinct motor neuron subtypes, specifically in defined subsets of limb-innervating motor pools that correlate with the loss of force-generating alpha motor neurons. Mechanistically, GDE2 is expressed by postmitotic motor neurons but utilizes extracellular glycerophosphodiester phosphodiesterase activity to induce motor neuron generation by inhibiting Notch signaling in neighboring motor neuron progenitors. Thus, neuronal GDE2 controls motor neuron subtype diversity through a non-cell-autonomous feedback mechanism that directly regulates progenitor cell differentiation, implying that subtype specification initiates within motor neuron progenitor populations prior to their differentiation into postmitotic motor neurons.
... REGULATIONS DRIVING OF COMMERCIAL MOTOR VEHICLES Stopped Commercial Motor Vehicles § 392.22 Emergency signals... activate the vehicular hazard warning signal flashers and continue the flashing until the driver places the warning devices required by paragraph (b) of this section. The flashing signals shall be used during...
... REGULATIONS DRIVING OF COMMERCIAL MOTOR VEHICLES Stopped Commercial Motor Vehicles § 392.22 Emergency signals... activate the vehicular hazard warning signal flashers and continue the flashing until the driver places the warning devices required by paragraph (b) of this section. The flashing signals shall be used during...
... REGULATIONS DRIVING OF COMMERCIAL MOTOR VEHICLES Stopped Commercial Motor Vehicles § 392.22 Emergency signals... activate the vehicular hazard warning signal flashers and continue the flashing until the driver places the warning devices required by paragraph (b) of this section. The flashing signals shall be used during...
Hofmann, Volker; Geurten, Bart R. H.; Sanguinetti-Scheck, Juan I.; Gómez-Sena, Leonel; Engelmann, Jacob
Motor patterns displayed during active electrosensory acquisition of information seem to be an essential part of a sensory strategy by which weakly electric fish actively generate and shape sensory flow. These active sensing strategies are expected to adaptively optimize ongoing behavior with respect to either motor efficiency or sensory information gained. The tight link between the motor domain and sensory perception in active electrolocation make weakly electric fish like Gnathonemus petersii an ideal system for studying sensory-motor interactions in the form of active sensing strategies. Analyzing the movements and electric signals of solitary fish during unrestrained exploration of objects in the dark, we here present the first formal quantification of motor patterns used by fish during electrolocation. Based on a cluster analysis of the kinematic values we categorized the basic units of motion. These were then analyzed for their associative grouping to identify and extract short coherent chains of behavior. This enabled the description of sensory behavior on different levels of complexity: from single movements, over short behaviors to more complex behavioral sequences during which the kinematics alter between different behaviors. We present detailed data for three classified patterns and provide evidence that these can be considered as motor components of active sensing strategies. In accordance with the idea of active sensing strategies, we found categorical motor patterns to be modified by the sensory context. In addition these motor patterns were linked with changes in the temporal sampling in form of differing electric organ discharge frequencies and differing spatial distributions. The ability to detect such strategies quantitatively will allow future research to investigate the impact of such behaviors on sensing. PMID:24904337
Brinning, Dorothy; And Others
Perceptual motor activities for physically handicapped children are presented in the areas of fine and gross motor skills. Also detailed are activities to develop body image, visual motor skills, and tactile and auditory perception. (JD)
Fautrelle, Lilian; Mareschal, Denis; French, Robert; Addyman, Caspar; Thomas, Elizabeth
Certain brain areas involved in interval timing are also important in motor activity. This raises the possibility that motor activity might influence interval timing. To test this hypothesis, we assessed interval timing in healthy adults following different types of training. The pre- and post-training tasks consisted of a button press in response to the presentation of a rhythmic visual stimulus. Alterations in temporal expectancy were evaluated by measuring response times. Training consisted of responding to the visual presentation of regularly appearing stimuli by either: (1) pointing with a whole-body movement, (2) pointing only with the arm, (3) imagining pointing with a whole-body movement, (4) simply watching the stimulus presentation, (5) pointing with a whole-body movement in response to a target that appeared at irregular intervals (6) reading a newspaper. Participants performing a motor activity in response to the regular target showed significant improvements in judgment times compared to individuals with no associated motor activity. Individuals who only imagined pointing with a whole-body movement also showed significant improvements. No improvements were observed in the group that trained with a motor response to an irregular stimulus, hence eliminating the explanation that the improved temporal expectations of the other motor training groups was purely due to an improved motor capacity to press the response button. All groups performed a secondary task equally well, hence indicating that our results could not simply be attributed to differences in attention between the groups. Our results show that motor activity, even when it does not play a causal or corrective role, can lead to improved interval timing judgments. PMID:25806813
Kimpo, Rhea R; Rinaldi, Jacob M; Kim, Christina K; Payne, Hannah L; Raymond, Jennifer L
Cerebellar climbing fiber activity encodes performance errors during many motor learning tasks, but the role of these error signals in learning has been controversial. We compared two motor learning paradigms that elicited equally robust putative error signals in the same climbing fibers: learned increases and decreases in the gain of the vestibulo-ocular reflex (VOR). During VOR-increase training, climbing fiber activity on one trial predicted changes in cerebellar output on the next trial, and optogenetic activation of climbing fibers to mimic their encoding of performance errors was sufficient to implant a motor memory. In contrast, during VOR-decrease training, there was no trial-by-trial correlation between climbing fiber activity and changes in cerebellar output, and climbing fiber activation did not induce VOR-decrease learning. Our data suggest that the ability of climbing fibers to induce plasticity can be dynamically gated in vivo, even under conditions where climbing fibers are robustly activated by performance errors. DOI: http://dx.doi.org/10.7554/eLife.02076.001 PMID:24755290
Batres-Mendoza, Patricia; Montoro-Sanjose, Carlos R.; Guerra-Hernandez, Erick I.; Almanza-Ojeda, Dora L.; Rostro-Gonzalez, Horacio; Romero-Troncoso, Rene J.; Ibarra-Manzano, Mario A.
Quaternions can be used as an alternative to model the fundamental patterns of electroencephalographic (EEG) signals in the time domain. Thus, this article presents a new quaternion-based technique known as quaternion-based signal analysis (QSA) to represent EEG signals obtained using a brain-computer interface (BCI) device to detect and interpret cognitive activity. This quaternion-based signal analysis technique can extract features to represent brain activity related to motor imagery accurately in various mental states. Experimental tests in which users where shown visual graphical cues related to left and right movements were used to collect BCI-recorded signals. These signals were then classified using decision trees (DT), support vector machine (SVM) and k-nearest neighbor (KNN) techniques. The quantitative analysis of the classifiers demonstrates that this technique can be used as an alternative in the EEG-signal modeling phase to identify mental states. PMID:26959029
Batres-Mendoza, Patricia; Montoro-Sanjose, Carlos R; Guerra-Hernandez, Erick I; Almanza-Ojeda, Dora L; Rostro-Gonzalez, Horacio; Romero-Troncoso, Rene J; Ibarra-Manzano, Mario A
Quaternions can be used as an alternative to model the fundamental patterns of electroencephalographic (EEG) signals in the time domain. Thus, this article presents a new quaternion-based technique known as quaternion-based signal analysis (QSA) to represent EEG signals obtained using a brain-computer interface (BCI) device to detect and interpret cognitive activity. This quaternion-based signal analysis technique can extract features to represent brain activity related to motor imagery accurately in various mental states. Experimental tests in which users where shown visual graphical cues related to left and right movements were used to collect BCI-recorded signals. These signals were then classified using decision trees (DT), support vector machine (SVM) and k-nearest neighbor (KNN) techniques. The quantitative analysis of the classifiers demonstrates that this technique can be used as an alternative in the EEG-signal modeling phase to identify mental states.
... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Motor activity. 798.6200 Section 798... (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Neurotoxicity § 798.6200 Motor activity. (a) Purpose—(1... the effects of administration of the substance on motor activity is useful when neurotoxicity...
Bahrami, Naghmeh; Bayat, Mohammad; Mohamadnia, Abdolreza; Khakbiz, Mehrdad; Yazdankhah, Meysam; Ai, Jafar; Ebrahimi-Barough, Somayeh
There is variety of stem cell sources but problems in ethical issues, contamination, and normal karyotype cause many limitations in obtaining and using these cells. The cells in Wharton's jelly region of umbilical cord are abundant and available stem cells with low immunological incompatibility, which could be considered for cell replacement therapy. Small molecules have been presented as less expensive biologically active compounds that can regulate different developmental process. Purmorphamine (PMA) is a small molecule that, according to some studies, possesses certain differentiation effects. In this study, we investigated the effect of the PMA on Wharton's jelly mesenchymal stem cell (WJ-MSC) differentiation into motor neuronal lineages instead of sonic hedgehog (Shh) on PCL scaffold. After exposing to induction media for 15 days, the cells were characterized for expression of motor neuron markers including PAX6, NF-H, Islet1, HB9, and choline acetyl transferase (ChAT) by quantitative reverse transcription (PCR) and immunocytochemistry. Our results demonstrated that induced WJ-MSCs with PMA could significantly express motor neuron markers in RNA and protein levels 15 days post induction. These results suggested that WJ-MSCs can differentiate to motor neuron-like cells with PMA on PCL scaffold and might provide a potential source in cell therapy for nervous system.
Matsunaga, Teruyuki; Kohsaka, Hiroshi; Nose, Akinao
In this study, we used the peristaltic crawling of Drosophila larvae as a model to study how motor patterns are regulated by central circuits. We built an experimental system that allows simultaneous application of optogenetics and calcium imaging to the isolated ventral nerve cord (VNC). We then investigated the effects of manipulating local activity of motor neurons (MNs) on fictive locomotion observed as waves of MN activity propagating along neuromeres. Optical inhibition of MNs with halorhodopsin3 in a middle segment (A4, A5, or A6), but not other segments, dramatically decreased the frequency of the motor waves. Conversely, local activation of MNs with channelrhodopsin2 in a posterior segment (A6 or A7) increased the frequency of the motor waves. Since peripheral nerves mediating sensory feedback were severed in the VNC preparation, these results indicate that MNs send signals to the central circuits to regulate motor pattern generation. Our results also indicate segmental specificity in the roles of MNs in motor control. The effects of the local MN activity manipulation were lost in shaking-B(2) (shakB(2) ) or ogre(2) , gap-junction mutations in Drosophila, or upon acute application of the gap junction blocker carbenoxolone, implicating electrical synapses in the signaling from MNs. Cell-type-specific RNAi suggested shakB and ogre function in MNs and interneurons, respectively, during the signaling. Our results not only reveal an unexpected role for MNs in motor pattern regulation, but also introduce a powerful experimental system that enables examination of the input-output relationship among the component neurons in this system.SIGNIFICANCE STATEMENT Motor neurons are generally considered passive players in motor pattern generation, simply relaying information from upstream interneuronal circuits to the target muscles. This study shows instead that MNs play active roles in the control of motor generation by conveying information via gap junctions to the
Yun, Mikyung; Zhang, Xiaohua; Park, Cheon-Gil; Park, Hee-Won; Endow, Sharyn A.
Molecular motors move along actin or microtubules by rapidly hydrolyzing ATP and undergoing changes in filament-binding affinity with steps of the nucleotide hydrolysis cycle. It is generally accepted that motor binding to its filament greatly increases the rate of ATP hydrolysis, but the structural changes in the motor associated with ATPase activation are not known. To identify the conformational changes underlying motor movement on its filament, we solved the crystal structures of three kinesin mutants that decouple nucleotide and microtubule binding by the motor, and block microtubule-activated, but not basal, ATPase activity. Conformational changes in the structures include a disordered loop and helices in the switch I region and a visible switch II loop, which is disordered in wild-type structures. Switch I moved closer to the bound nucleotide in two mutant structures, perturbing water-mediated interactions with the Mg2+. This could weaken Mg2+ binding and accelerate ADP release to activate the motor ATPase. The structural changes we observe define a signaling pathway within the motor for ATPase activation that is likely to be essential for motor movement on microtubules. PMID:11387196
Rioult-Pedotti, Mengia-Seraina; Pekanovic, Ana; Atiemo, Clement Osei; Marshall, John; Luft, Andreas Rüdiger
Dopaminergic neurons in the ventral tegmental area, the major midbrain nucleus projecting to the motor cortex, play a key role in motor skill learning and motor cortex synaptic plasticity. Dopamine D1 and D2 receptor antagonists exert parallel effects in the motor system: they impair motor skill learning and reduce long-term potentiation. Traditionally, D1 and D2 receptor modulate adenylyl cyclase activity and cyclic adenosine monophosphate accumulation in opposite directions via different G-proteins and bidirectionally modulate protein kinase A (PKA), leading to distinct physiological and behavioral effects. Here we show that D1 and D2 receptor activity influences motor skill acquisition and long term synaptic potentiation via phospholipase C (PLC) activation in rat primary motor cortex. Learning a new forelimb reaching task is severely impaired in the presence of PLC, but not PKA-inhibitor. Similarly, long term potentiation in motor cortex, a mechanism involved in motor skill learning, is reduced when PLC is inhibited but remains unaffected by the PKA inhibitor. Skill learning deficits and reduced synaptic plasticity caused by dopamine antagonists are prevented by co-administration of a PLC agonist. These results provide evidence for a role of intracellular PLC signaling in motor skill learning and associated cortical synaptic plasticity, challenging the traditional view of bidirectional modulation of PKA by D1 and D2 receptors. These findings reveal a novel and important action of dopamine in motor cortex that might be a future target for selective therapeutic interventions to support learning and recovery of movement resulting from injury and disease.
Akay, T; Bässler, U; Gerharz, P; Büschges, A
Interjoint coordination in multi-jointed limbs is essential for the generation of functional locomotor patterns. Here we have focused on the role that sensory signals from the coxa-trochanteral (CT) joint play in patterning motoneuronal activity of the femur-tibia (FT) joint in the stick insect middle leg. This question is of interest because when the locomotor system is active, movement signals from the FT joint are known to contribute to patterning of activity of the central rhythm-generating networks governing the CT joint. We investigated the influence of femoral levation and depression on the activity of tibial motoneurons. When the locomotor system was active, levation of the femur often induced a decrease or inactivation of tibial extensor activity while flexor motoneurons were activated. Depression of the femur had no systematic influence on tibial motoneurons. Ablation experiments revealed that this interjoint influence was not mediated by signals from movement and/or position sensitive receptors at the CT joint, i.e., trochanteral hairplate, rhombal hairplate, or internal levator receptor organ. Instead the influence was initiated by sensory signals from a field of campaniform sensillae, situated on the proximal femur (fCS). Selective stimulation of these fCS produced barrages of inhibitory postsynaptic potentials (IPSPs) in tibial extensor motoneurons and activated tibial flexor motoneurons. During pharmacologically activated rhythmic activity of the otherwise isolated mesothoracic ganglion (pilocarpine, 5 x 10(-4) M), deafferented except for the CT joint, levation of the femur as well had an inhibitory influence on tibial extensor motoneurons. However, the influence of femoral levation on the rhythm generated was rather labile and only sometimes a reset of the rhythm was induced. In none of the preparations could entrainment of rhythmicity by femoral movement be achieved, suggesting that sensory signals from the CT joint only weakly affect central
Brinning, Dorothy; And Others
Designed for parents, the guide offers instructions for home activities to supplement the school program for children with perceptual motor disturbances. An individual program sheet is provided; behavioral characteristics and the child's need for structure are explained. Activities detailed include motor planning, body image, fine motor…
Iso, Naoki; Moriuchi, Takefumi; Sagari, Akira; Kitajima, Eiji; Iso, Fumiko; Tanaka, Koji; Kikuchi, Yasuki; Tabira, Takayuki; Higashi, Toshio
The aim of this study was to clarify the topographical localization of motor-related regional hemodynamic signal changes during motor execution (ME) and motor imagery (MI) by using near-infrared spectroscopy (NIRS), as this technique is more clinically expedient than established methods (e.g., fMRI). Twenty right-handed healthy subjects participated in this study. The experimental protocol was a blocked design consisting of 3 cycles of 20 s of task performance and 30 s of rest. The tapping sequence task was performed with their fingers under 4 conditions: ME and MI with the right or left hand. Hemodynamic brain activity was measured with NIRS to monitor changes in oxygenated hemoglobin (oxy-Hb) concentration. Oxy-Hb in the somatosensory motor cortex (SMC) increased significantly only during contralateral ME and showed a significant interaction between task and hand. There was a main effect of hand in the left SMC. Although there were no significant main effects or interactions in the supplemental motor area (SMA) and premotor area (PMA), oxy-Hb increased substantially under all conditions. These results clarified the topographical localization by motor-related regional hemodynamic signal changes during ME and MI by using NIRS. PMID:26793118
Iso, Naoki; Moriuchi, Takefumi; Sagari, Akira; Kitajima, Eiji; Iso, Fumiko; Tanaka, Koji; Kikuchi, Yasuki; Tabira, Takayuki; Higashi, Toshio
The aim of this study was to clarify the topographical localization of motor-related regional hemodynamic signal changes during motor execution (ME) and motor imagery (MI) by using near-infrared spectroscopy (NIRS), as this technique is more clinically expedient than established methods (e.g., fMRI). Twenty right-handed healthy subjects participated in this study. The experimental protocol was a blocked design consisting of 3 cycles of 20 s of task performance and 30 s of rest. The tapping sequence task was performed with their fingers under 4 conditions: ME and MI with the right or left hand. Hemodynamic brain activity was measured with NIRS to monitor changes in oxygenated hemoglobin (oxy-Hb) concentration. Oxy-Hb in the somatosensory motor cortex (SMC) increased significantly only during contralateral ME and showed a significant interaction between task and hand. There was a main effect of hand in the left SMC. Although there were no significant main effects or interactions in the supplemental motor area (SMA) and premotor area (PMA), oxy-Hb increased substantially under all conditions. These results clarified the topographical localization by motor-related regional hemodynamic signal changes during ME and MI by using NIRS.
Pape, Anna-Antonia; Siegel, Markus
Our actions are constantly guided by decisions based on sensory information. The motor cortex is traditionally viewed as the final output stage in this process, merely executing motor responses based on these decisions. However, it is not clear if, beyond this role, the motor cortex itself impacts response selection. Here, we report activity fluctuations over motor cortex measured using MEG, which are unrelated to choice content and predict responses to a visuomotor task seconds before decisions are made. These fluctuations are strongly influenced by the previous trial's response and predict a tendency to switch between response alternatives for consecutive decisions. This alternation behaviour depends on the size of neural signals still present from the previous response. Our results uncover a response-alternation bias in sensorimotor decision making. Furthermore, they suggest that motor cortex is more than an output stage and instead shapes response selection during sensorimotor decision making. PMID:27713396
Voon, Valerie; Brezing, Christina; Gallea, Cecile; Hallett, Mark
Conversion disorder (CD) is characterized by unexplained neurological symptoms presumed related to psychological issues. The main hypotheses to explain conversion paralysis, characterized by a lack of movement, include impairments in either motor intention or disruption of motor execution, and further, that hyperactive self-monitoring, limbic processing or top-down regulation from higher order frontal regions may interfere with motor execution. We have recently shown that CD with positive abnormal or excessive motor symptoms was associated with greater amygdala activity to arousing stimuli along with greater functional connectivity between the amygdala and supplementary motor area. Here we studied patients with such symptoms focusing on motor initiation. Subjects performed either an internally or externally generated 2-button action selection task in a functional MRI study. Eleven CD patients without major depression and 11 age- and gender-matched normal volunteers were assessed. During both internally and externally generated movement, conversion disorder patients relative to normal volunteers had lower left supplementary motor area (SMA) (implicated in motor initiation) and higher right amygdala, left anterior insula, and bilateral posterior cingulate activity (implicated in assigning emotional salience). These findings were confirmed in a subgroup analysis of patients with tremor symptoms. During internally versus externally generated action in CD patients, the left SMA had lower functional connectivity with bilateral dorsolateral prefrontal cortices. We propose a theory in which previously mapped conversion motor representations may in an arousing context hijack the voluntary action selection system, which is both hypoactive and functionally disconnected from prefrontal top-down regulation.
Cratty, Bryant J.
Presented are chapters concerned with the relationship of motor activity to education. The topics discussed are research, movement and performance in infants and children, principles of teaching motor skills; arousal level and attention; scribbling, drawing, writing, strength, flexibility, endurance, and control of large muscles; music and rhythm;…
Beltran-Carbajal, F.; Valderrabano-Gonzalez, A.; Rosas-Caro, J. C.
An asymptotic differentiation approach with respect to time is used for on-line estimation of velocity and acceleration signals in controlled dc motors. The attractive feature of this differentiator of signals is that it does not require any system mathematical model, which allows its use in engineering systems that require the signal differentiation for its control, identification, fault detection, among other applications. Moreover, it is shown that the differentiation approach can be applied for output signals showing a chaotic behavior. In addition a differential flatness control scheme with additional integral compensation of the output error is proposed for tracking tasks of position reference trajectories for direct current electric motors using angular position measurements only.
... systematically related to treatment. Among the variables which can affect motor activity are sound level, size and shape of the test cage, temperature, relative humidity, lighting conditions, odors, use of...
... systematically related to treatment. Among the variables which can affect motor activity are sound level, size and shape of the test cage, temperature, relative humidity, lighting conditions, odors, use of...
Sedov, A S; Raeva, S N; Pavlenko, V B
Neural mechanisms of motor signal transmission in ventrooral (Voi) nucleus of motor thalamus during the realization-of voluntary and involuntary abnormal (dystonic) movements in patients with spasmodic torticollis were investigated by means of microelectrode technique. The high reactivity of the cellular Voi elements to various functional (mainly motor) tests was proved. Analysis of neuronal activity showed: (1) the difference of neural mechanisms of motor signal transmission in the realization of voluntary movement with and without the involvement of the pathological axial neck muscles, as well as passive and abnormal involuntary dystonic movements; (2) significance of sensory component in the mechanisms of sensorimotor interactions during realization of voluntary and involuntary dystonic head and neck movements, causing the activation of the axial neck muscles; (3) important role of the rhythmic and synchronized neuronal activity in motor signal transmission during the realization of active and passive movements. Participation of Voi nucleus in pathological mechanisms of spasmodic torticollis was shown. The data obtained can be used for identificatiori of Voi thalamic nucleus during stereotactic neurosurgical operations in patients with spasmodic torticollis for selection the optimum destruction (stimulation) target and reduction of postoperative effects.
Ottewill, J. R.; Orkisz, M.
Due to their prevalence in rotating machinery, the condition monitoring of gearboxes is extremely important in the minimization of potentially dangerous and expensive failures. Traditionally, gearbox condition monitoring has been conducted using measurements obtained from casing-mounted vibration transducers such as accelerometers. A well-established technique for analyzing such signals is the synchronous signal average, where vibration signals are synchronized to a measured angular position and then averaged from rotation to rotation. Driven, in part, by improvements in control methodologies based upon methods of estimating rotor speed and torque, induction machines are used increasingly in industry to drive rotating machinery. As a result, attempts have been made to diagnose defects using measured terminal currents and voltages. In this paper, the application of the synchronous signal averaging methodology to electric drive signals, by synchronizing stator current signals with a shaft position estimated from current and voltage measurements is proposed. Initially, a test-rig is introduced based on an induction motor driving a two-stage reduction gearbox which is loaded by a DC motor. It is shown that a defect seeded into the gearbox may be located using signals acquired from casing-mounted accelerometers and shaft mounted encoders. Using simple models of an induction motor and a gearbox, it is shown that it should be possible to observe gearbox defects in the measured stator current signal. A robust method of extracting the average speed of a machine from the current frequency spectrum, based on the location of sidebands of the power supply frequency due to rotor eccentricity, is presented. The synchronous signal averaging method is applied to the resulting estimations of rotor position and torsional vibration. Experimental results show that the method is extremely adept at locating gear tooth defects. Further results, considering different loads and different
Marlinski, Vladimir; Nilaweera, Wijitha U.; Zelenin, Pavel V.; Sirota, Mikhail G.
The activity of the motor cortex during locomotion is profoundly modulated in the rhythm of strides. The source of modulation is not known. In this study we examined the activity of one of the major sources of afferent input to the motor cortex, the ventrolateral thalamus (VL). Experiments were conducted in chronically implanted cats with an extracellular single-neuron recording technique. VL neurons projecting to the motor cortex were identified by antidromic responses. During locomotion, the activity of 92% of neurons was modulated in the rhythm of strides; 67% of cells discharged one activity burst per stride, a pattern typical for the motor cortex. The characteristics of these discharges in most VL neurons appeared to be well suited to contribute to the locomotion-related activity of the motor cortex. In addition to simple locomotion, we examined VL activity during walking on a horizontal ladder, a task that requires vision for correct foot placement. Upon transition from simple to ladder locomotion, the activity of most VL neurons exhibited the same changes that have been reported for the motor cortex, i.e., an increase in the strength of stride-related modulation and shortening of the discharge duration. Five modes of integration of simple and ladder locomotion-related information were recognized in the VL. We suggest that, in addition to contributing to the locomotion-related activity in the motor cortex during simple locomotion, the VL integrates and transmits signals needed for correct foot placement on a complex terrain to the motor cortex. PMID:21994259
Soe, Ni Ni; Nakagawa, Masahiro
This paper presents the novel approach to evaluate the effects of different motor activation tasks of the human electroencephalogram (EEG). The applications of chaos and fractal properties that are the most important tools in nonlinear analysis are been presented for four tasks of EEG during the real and imaginary motor movement. Three subjects, aged 23-30 years, participated in the experiment. Correlation dimension (D2), Lyapunov spectrum (λi), and Lyapunov dimension (DL) are been estimated to characterize the movement related EEG signals. Experimental results show that these nonlinear measures are good discriminators of EEG signals. There are significant differences in all conditions of subjective task. The fractal dimension appeared to be higher in movement conditions compared to the baseline condition. It is concluded that chaos and fractal analysis could be powerful methods in investigating brain activities during motor movements.
Nelson, Anders; Schneider, David M.; Takatoh, Jun; Sakurai, Katsuyasu; Wang, Fan
Normal hearing depends on the ability to distinguish self-generated sounds from other sounds, and this ability is thought to involve neural circuits that convey copies of motor command signals to various levels of the auditory system. Although such interactions at the cortical level are believed to facilitate auditory comprehension during movements and drive auditory hallucinations in pathological states, the synaptic organization and function of circuitry linking the motor and auditory cortices remain unclear. Here we describe experiments in the mouse that characterize circuitry well suited to transmit motor-related signals to the auditory cortex. Using retrograde viral tracing, we established that neurons in superficial and deep layers of the medial agranular motor cortex (M2) project directly to the auditory cortex and that the axons of some of these deep-layer cells also target brainstem motor regions. Using in vitro whole-cell physiology, optogenetics, and pharmacology, we determined that M2 axons make excitatory synapses in the auditory cortex but exert a primarily suppressive effect on auditory cortical neuron activity mediated in part by feedforward inhibition involving parvalbumin-positive interneurons. Using in vivo intracellular physiology, optogenetics, and sound playback, we also found that directly activating M2 axon terminals in the auditory cortex suppresses spontaneous and stimulus-evoked synaptic activity in auditory cortical neurons and that this effect depends on the relative timing of motor cortical activity and auditory stimulation. These experiments delineate the structural and functional properties of a corticocortical circuit that could enable movement-related suppression of auditory cortical activity. PMID:24005287
Nelson, Anders; Schneider, David M; Takatoh, Jun; Sakurai, Katsuyasu; Wang, Fan; Mooney, Richard
Normal hearing depends on the ability to distinguish self-generated sounds from other sounds, and this ability is thought to involve neural circuits that convey copies of motor command signals to various levels of the auditory system. Although such interactions at the cortical level are believed to facilitate auditory comprehension during movements and drive auditory hallucinations in pathological states, the synaptic organization and function of circuitry linking the motor and auditory cortices remain unclear. Here we describe experiments in the mouse that characterize circuitry well suited to transmit motor-related signals to the auditory cortex. Using retrograde viral tracing, we established that neurons in superficial and deep layers of the medial agranular motor cortex (M2) project directly to the auditory cortex and that the axons of some of these deep-layer cells also target brainstem motor regions. Using in vitro whole-cell physiology, optogenetics, and pharmacology, we determined that M2 axons make excitatory synapses in the auditory cortex but exert a primarily suppressive effect on auditory cortical neuron activity mediated in part by feedforward inhibition involving parvalbumin-positive interneurons. Using in vivo intracellular physiology, optogenetics, and sound playback, we also found that directly activating M2 axon terminals in the auditory cortex suppresses spontaneous and stimulus-evoked synaptic activity in auditory cortical neurons and that this effect depends on the relative timing of motor cortical activity and auditory stimulation. These experiments delineate the structural and functional properties of a corticocortical circuit that could enable movement-related suppression of auditory cortical activity.
Yang, Wei; Burkhardt, Britta; Fischer, Luise; Beirow, Maja; Bork, Nadja; Wönne, Eva C.; Wagner, Cornelia; Husen, Bettina; Zeilinger, Katrin; Liu, Liegang; Nussler, Andreas K.
Aging is characterized by a progressive decrease of cellular functions, because cells gradually lose their capacity to respond to injury. Increased oxidative stress is considered to be one of the major contributors to age-related changes in all organs including the liver. Our study has focused on elucidating whether important antioxidative enzymes, the mTOR pathway, and MAPKs exhibit age-dependent changes in the liver of rats during aging. We found an age-dependent increase of GSH in the cytosol and mitochondria. The aged liver showed an increased SOD enzyme activity, while the CAT enzyme activity decreased. HO-1 and NOS-2 gene expression was lower in adult rats, but up-regulated in aged rats. Western blot analysis revealed that SOD1, SOD2, GPx, GR, γ-GCL, and GSS were age-dependent up-regulated, while CAT remained constant. We also demonstrated that the phosphorylation of Akt, JNK, p38, and TSC2Ser1254 decreased while ERK1/2 and TSC2Thr1462 increased age-dependently. Furthermore, our data show that the mTOR pathway seems to be activated in livers of aged rats, and hence stimulating cell proliferation/regeneration, as confirmed by an age-dependent increase of PCNA and p-eIF4ESer209 protein expression. Our data may help to explain the fact that liver cells only proliferate in cases of necessity, like injury and damage. In summary, we have demonstrated that, age-dependent changes of the antioxidant system and stress-related signaling pathways occur in the livers of rats, which may help to better understand organ aging. PMID:27004051
Eastman, Mary Kay; Safran, Joan S.
Instructions and illustrations support this discussion of learning activities designed to remediate deficiences and build skills in balance and/or motor skills for mildly handicapped students who may not have access to physical therapy or adaptive physical education. Appropriate for both regular and special classes, activities include arm…
Bondar', I V; Vasil'eva, L N; Badakva, A M; Miller, N V; Zobova, L N; Roshchin, V Iu
Disconnection of central and peripheral parts of motor system leads to severe forms of disability. However, current research of brain-computer interfaces will solve the problem of rehabilitation of patients with motor disorders in future. Chronic recordings of single-unit activity in specialized areas of cerebral cortex could provide appropriate control signal for effectors with multiple degrees of freedom. In present article we evaluated the quality of chronic single-unit recordings in the primary motor cortex of awake behaving monkeys obtained with bundles of multiple microwires. Action potentials of proper quality were recorded from single units during three months. In some cases up to 7 single units could be extracted on a channel. Recording quality stabilized after 40 days since electrodes were implanted. Ultimately, functionality of multiple electrodes bundle makes it highly usable and reliable instrument for obtaining of control neurophysiologic signal from populations of neurons for brain-computer interfaces.
Repeated Baclofen treatment ameliorates motor dysfunction, suppresses reflex activity and decreases the expression of signaling proteins in reticular nuclei and lumbar motoneurons after spinal trauma in rats.
Kucharíková, Andrea; Schreiberová, Andrea; Závodská, Monika; Gedrová, Štefánia; Hricová, Ľudmila; Pavel, Jaroslav; Gálik, Ján; Maršala, Martin; Lukáčová, Nadežda
The interruption of supraspinal input to the spinal cord leads to motor dysfunction and the development of spasticity. Clinical studies have shown that Baclofen (a GABAB agonist), while effective in modulating spasticity is associated with side-effects and the development of tolerance. The aim of the present study was to assess if discontinued Baclofen treatment and its repeated application leads antispasticity effects, and whether such changes affect neuronal nitric oxide synthase (nNOS) in the brainstem, nNOS and parvalbumin (PV) in lumbar α-motoneurons and glial fibrillary acidic protein in the ventral horn of the spinal cord. Adult male Wistar rats were exposed to Th9 spinal cord transection. Baclofen (30mg/b.w.) diluted in drinking water, was administered for 6 days, starting at week 1 after injury and then repeated till week 4 after injury. The behavior of the animals was tested (tail-flick test, BBB locomotor score) from 1 to 8 weeks. Our results clearly indicate the role of nitric oxide, produced by nNOS in the initiation and the maintenance of spasticity states 1, 6 and 8 weeks after spinal trauma. A considerable decrease of nNOS staining after Baclofen treatment correlates with improvement of motor dysfunction. The findings also show that parvalbumin and astrocytes participate in the regulation of ion concentrations in the sub-acute phase after the injury.
Zhang, Jiang; Yuan, Zhen; Huang, Jin; Yang, Qin; Chen, Huafu
Motor imagery is an experimental paradigm implemented in cognitive neuroscience and cognitive psychology. To investigate the asymmetry of the strength of cortical functional activity due to different single-hand motor imageries, functional magnetic resonance imaging (fMRI) data from right handed normal subjects were recorded and analyzed during both left-hand and right-hand motor imagery processes. Then the average power of blood oxygenation level-dependent (BOLD) signals in temporal domain was calculated using the developed tool that combines Welch power spectrum and the integral of power spectrum approach of BOLD signal changes during motor imagery. Power change analysis results indicated that cortical activity exhibited a stronger power in the precentral gyrus and medial frontal gyrus with left-hand motor imagery tasks compared with that from right-hand motor imagery tasks. These observations suggest that right handed normal subjects mobilize more cortical nerve cells for left-hand motor imagery. Our findings also suggest that the approach based on power differences of BOLD signals is a suitable quantitative analysis tool for quantification of asymmetry of brain activity intensity during motor imagery tasks.
Nutsch, Torsten; Marwan, Wolfgang; Oesterhelt, Dieter; Gilles, Ernst Dieter
Prokaryotic taxis, the active search of motile cells for the best environmental conditions, is one of the paradigms for signal transduction. The search algorithm implemented by the cellular biochemistry modulates the probability of switching the rotational direction of the flagellar motor, a nanomachine that propels prokaryotic cells. On the basis of the well-known biochemical mechanisms of chemotaxis in Escherichia coli, kinetic modeling of the events leading from chemoreceptor activation by ligand binding to the motility response has been performed with great success. In contrast to Escherichia coli, Halobacterium salinarum, in addition, responds to visible light, which is sensed through specific photoreceptors of different wavelength sensitivity (phototaxis). Light stimuli of defined intensity and time course can be controlled precisely, which facilitates input-output measurements used for system analysis of the molecular network connecting the sensory receptors to the flagellar motor switch. Here, we analyze the response of halobacterial cells to single and double-pulse light stimuli and present the first kinetic model for prokaryotic cells that couples the signal-transduction pathway with the flagellar motor switch. Modeling based on experimental data supports the current biochemical model of halobacterial phototaxis. Moreover, the simulations demonstrate that motor switching occurs through subsequent rate-limiting steps, which are both under sensory control, suggesting that two signals may be involved in halobacterial phototaxis.
Ebbesen, Christian Laut; Doron, Guy; Lenschow, Constanze; Brecht, Michael
Anatomical, stimulation and lesion data implicate vibrissa motor cortex in whisker motor control. Work on motor cortex has focused on movement generation, but correlations between vibrissa motor cortex activity and whisking are weak. The exact role of vibrissa motor cortex remains unknown. We recorded vibrissa motor cortex neurons during various forms of vibrissal touch, which were invariably associated with whisker protraction and movement. Free whisking, object palpation and social touch all resulted in decreased cortical activity. To understand this activity decrease, we performed juxtacellular recordings, nanostimulation and in vivo whole-cell recordings. Social touch resulted in decreased spiking activity, decreased cell excitability and membrane hyperpolarization. Activation of vibrissa motor cortex by intracortical microstimulation elicited whisker retraction, as if to abort vibrissal touch. Various vibrissa motor cortex inactivation protocols resulted in contralateral protraction and increased whisker movements. These data collectively point to movement suppression as a prime function of vibrissa motor cortex activity.
Dale, Erica A.; Satriotomo, Irawan; Mitchell, Gordon S.
Erythropoietin (EPO) is typically known for its role in erythropoiesis, but is also a potent neurotrophic/neuroprotective factor for spinal motor neurons. Another trophic factor regulated by Hypoxia-Inducible Factor-1, vascular endothelial growth factor (VEGF), signals via ERK and Akt activation to elicit long-lasting phrenic motor facilitation (pMF). Since EPO also signals via ERK and Akt activation, we tested the hypothesis that EPO elicits similar pMF. Using retrograde labeling and immunohistochemical techniques, we demonstrate in adult, male, Sprague-Dawley rats that EPO and its receptor, EPO-R, are expressed in identified phrenic motor neurons. Intrathecal EPO at C4 elicits long-lasting pMF; integrated phrenic nerve burst amplitude increased >90 min post-injection (63±12% baseline 90 min post-injection; p<0.001). EPO increased phosphorylation (and presumed activation) of ERK (1.6 fold vs controls; p<0.05) in phrenic motor neurons; EPO also increased pAkt (1.6 fold vs controls; p<0.05). EPO-induced pMF was abolished by the MEK/ERK inhibitor U0126 and the PI3 kinase/Akt inhibitor LY294002, demonstrating that ERK MAP kinases and Akt are both required for EPO-induced pMF. Pre-treatment with U0126 and LY294002 decreased both pERK and pAkt in phrenic motor neurons (p<0.05), indicating a complex interaction between these kinases. We conclude that EPO elicits spinal plasticity in respiratory motor control. Since EPO expression is hypoxia-sensitive, it may play a role in respiratory plasticity in conditions of prolonged or recurrent low oxygen. PMID:22539857
Li, Junhua; Zhang, Liqing
Brain-computer interface (BCI) allows the use of brain activities for people to directly communicate with the external world or to control external devices without participation of any peripheral nerves and muscles. Motor imagery is one of the most popular modes in the research field of brain-computer interface. Although motor imagery BCI has some advantages compared with other modes of BCI, such as asynchronization, it is necessary to require training sessions before using it. The performance of trained BCI system depends on the quality of training samples or the subject engagement. In order to improve training effect and decrease training time, we proposed a new paradigm where subjects participated in training more actively than in the traditional paradigm. In the traditional paradigm, a cue (to indicate what kind of motor imagery should be imagined during the current trial) is given to the subject at the beginning of a trial or during a trial, and this cue is also used as a label for this trial. It is usually assumed that labels for trials are accurate in the traditional paradigm, although subjects may not have performed the required or correct kind of motor imagery, and trials may thus be mislabeled. And then those mislabeled trials give rise to interference during model training. In our proposed paradigm, the subject is required to reconfirm the label and can correct the label when necessary. This active training paradigm may generate better training samples with fewer inconsistent labels because it overcomes mistakes when subject's motor imagination does not match the given cues. The experiments confirm that our proposed paradigm achieves better performance; the improvement is significant according to statistical analysis.
Butler, Andrew J.; James, Thomas W.; James, Karin Harman
Everyday experience affords us many opportunities to learn about objects through multiple senses using physical interaction. Previous work has shown that active motor learning of unisensory items enhances memory and leads to the involvement of motor systems during subsequent perception. However, the impact of active motor learning on subsequent…
Fields, D. P.; Springborn, S. R.
Spinal serotonin type 7 (5-HT7) receptors elicit complex effects on motor activity. Whereas 5-HT7 receptor activation gives rise to long-lasting phrenic motor facilitation (pMF), it also constrains 5-HT2 receptor-induced pMF via “cross-talk inhibition.” We hypothesized that divergent cAMP-dependent signaling pathways give rise to these distinct 5-HT7 receptor actions. Specifically, we hypothesized that protein kinase A (PKA) mediates cross-talk inhibition of 5-HT2 receptor-induced pMF whereas 5-HT7 receptor-induced pMF results from exchange protein activated by cAMP (EPAC) signaling. Anesthetized, paralyzed, and ventilated rats receiving intrathecal (C4) 5-HT7 receptor agonist (AS-19) injections expressed pMF for >90 min, an effect abolished by pretreatment with a selective EPAC inhibitor (ESI-05) but not a selective PKA inhibitor (KT-5720). Furthermore, intrathecal injections of a selective EPAC activator (8-pCPT-2′-Me-cAMP) were sufficient to elicit pMF. Finally, spinal mammalian target of rapamycin complex-1 (mTORC1) inhibition via intrathecal rapamycin abolished 5-HT7 receptor- and EPAC-induced pMF, demonstrating that spinal 5-HT7 receptors elicit pMF by an EPAC-mTORC1 signaling pathway. Thus 5-HT7 receptors elicit and constrain spinal phrenic motor plasticity via distinct signaling mechanisms that diverge at cAMP (EPAC vs. PKA). Selective manipulation of these molecules may enable refined regulation of serotonin-dependent spinal motor plasticity for therapeutic advantage. PMID:26269554
Fields, D P; Springborn, S R; Mitchell, G S
Spinal serotonin type 7 (5-HT7) receptors elicit complex effects on motor activity. Whereas 5-HT7 receptor activation gives rise to long-lasting phrenic motor facilitation (pMF), it also constrains 5-HT2 receptor-induced pMF via "cross-talk inhibition." We hypothesized that divergent cAMP-dependent signaling pathways give rise to these distinct 5-HT7 receptor actions. Specifically, we hypothesized that protein kinase A (PKA) mediates cross-talk inhibition of 5-HT2 receptor-induced pMF whereas 5-HT7 receptor-induced pMF results from exchange protein activated by cAMP (EPAC) signaling. Anesthetized, paralyzed, and ventilated rats receiving intrathecal (C4) 5-HT7 receptor agonist (AS-19) injections expressed pMF for >90 min, an effect abolished by pretreatment with a selective EPAC inhibitor (ESI-05) but not a selective PKA inhibitor (KT-5720). Furthermore, intrathecal injections of a selective EPAC activator (8-pCPT-2'-Me-cAMP) were sufficient to elicit pMF. Finally, spinal mammalian target of rapamycin complex-1 (mTORC1) inhibition via intrathecal rapamycin abolished 5-HT7 receptor- and EPAC-induced pMF, demonstrating that spinal 5-HT7 receptors elicit pMF by an EPAC-mTORC1 signaling pathway. Thus 5-HT7 receptors elicit and constrain spinal phrenic motor plasticity via distinct signaling mechanisms that diverge at cAMP (EPAC vs. PKA). Selective manipulation of these molecules may enable refined regulation of serotonin-dependent spinal motor plasticity for therapeutic advantage.
Alonso-Valerdi, Luz María; Sepulveda, Francisco
Brain Computer Interface (BCI) systems control the user's environment via his/her brain signals. Brain signals related to motor imagery (MI) have become a widespread method employed by the BCI community. Despite the large number of references describing the MI signal treatment, there is not enough information related to the available programming languages that could be suitable to develop a specific-purpose MI-based BCI. The present paper describes the development of an offline-analysis system based on MI-EEG signals via open-source programming languages, and the assessment of the system using electrical activity recorded from three subjects. The analyzer recognized at least 63% of the MI signals corresponding to three classes. The results of the offline analysis showed a promising performance considering that the subjects have never undergone MI trainings.
Bunno, Yoshibumi; Suzuki, Toshiaki; Iwatsuki, Hiroyasu
[Purpose] The aim of this study was to investigate the changes in spinal motor neuron excitability and autonomic nervous system activity during motor imagery of isometric thenar muscle activity at 10% and 50% maximal voluntary contraction (MVC). [Methods] The F-waves and low frequency/high frequency (LF/HF) ratio were recorded at rest, during motor imagery, and post-trial. For motor imagery trials, subjects were instructed to imagine thenar muscle activity at 10% and 50% MVC while holding the sensor of a pinch meter for 5 min. [Results] The F-waves and LF/HF ratio during motor imagery at 50% MVC were significantly increased compared with those at rest, whereas those during motor imagery at 10% MVC were not significantly different from those at rest. The relative values of the F/M amplitude ratio during motor imagery at 50% MVC were significantly higher than those at 10% MVC. The relative values of persistence and the LF/HF ratio during motor imagery were similar during motor imagery at the two muscle contraction strengths. [Conclusion] Motor imagery can increase the spinal motor neuron excitability and cardiac sympathetic nerve activity. Motor imagery at 50% MVC may be more effective than motor imagery at 10% MVC.
Jubeau, M; Gondin, J; Martin, A; Sartorio, A; Maffiuletti, N A
Whether the involvement of motor units is different between surface neuromuscular electrostimulation and voluntary activation remains an unresolved issue. The aim of this pilot study was to verify if motor unit activation during electrostimulation is nonselective/random (i.e., without obvious sequencing related to fibre type), as recently suggested by Gregory and Bickel . Sixteen healthy men randomly performed submaximal isometric contractions (10-s duration) of the quadriceps femoris muscle at 20, 40 and 60 % of maximal voluntary torque under both stimulated and voluntary conditions. During the contractions, paired stimuli were delivered to the femoral nerve (twitch interpolation technique) and the characteristics of the superimposed doublet were compared between the two conditions. For each torque level, time-to-peak torque was significantly longer (p range = 0.05 - 0.0002) during electrostimulation compared to voluntary contractions. Moreover, time-to-peak torque during voluntary trials decreased significantly when increasing the torque level from 20 to 60 % of maximal voluntary torque (p range = 0.03 - 0.0001), whereas it was unchanged during electrostimulation. In conclusion, over-the-muscle electrostimulation would neither result in motor unit recruitment according to Henneman's size principle nor would it result in a reversal in voluntary recruitment order. During electrostimulation, muscle fibres are activated without obvious sequencing related to fibre type.
Soetedjo, Robijanto; Fuchs, Albert F; Kojima, Yoshiko
How the brain learns and maintains accurate precision movements is currently unknown. At times throughout life, rapid gaze shifts (saccades) become inaccurate, but the brain makes gradual adjustments so they again stop on target. Previously, we showed that complex spikes (CSs) in Purkinje cells of the oculomotor cerebellum report the direction and amplitude by which saccades are in error. Anatomical studies indicate that this error signal could originate in the superior colliculus (SC). Here, we deliver subthreshold electrical stimulation of the SC after the saccade lands to signal an apparent error. The size of saccades in the same direction as the simulated error gradually increase; those in the opposite direction decrease. The electrically adapted saccades endure after stimulation is discontinued, exhibit an adaptation field, can undergo changes in direction, and depend on error timing. These electrically induced adaptations were virtually identical with those produced by the visually induced adaptations that we report here for comparable visual errors in the same monkeys. Therefore, our experiments reveal that an additional role for the SC in the generation of saccades is to provide a vector error signal that drives dysmetric saccades to adapt. Moreover, the characteristics of the electrically induced adaptation reflect those of error-related CS activity in the oculomotor cerebellum, suggesting that CS activity serves as the learning signal. We speculate that CS activity may serve as the error signal that drives other kinds of motor learning as well.
Bundy, David T.; Wronkiewicz, Mark; Sharma, Mohit; Moran, Daniel W.; Corbetta, Maurizio; Leuthardt, Eric C.
Brain-computer interface (BCI) systems have emerged as a method to restore function and enhance communication in motor impaired patients. To date, this has been applied primarily to patients who have a compromised motor outflow due to spinal cord dysfunction, but an intact and functioning cerebral cortex. The cortical physiology associated with movement of the contralateral limb has typically been the signal substrate that has been used as a control signal. While this is an ideal control platform in patients with an intact motor cortex, these signals are lost after a hemispheric stroke. Thus, a different control signal is needed that could provide control capability for a patient with a hemiparetic limb. Previous studies have shown that there is a distinct cortical physiology associated with ipsilateral, or same-sided, limb movements. Thus far, it was unknown whether stroke survivors could intentionally and effectively modulate this ipsilateral motor activity from their unaffected hemisphere. Therefore, this study seeks to evaluate whether stroke survivors could effectively utilize ipsilateral motor activity from their unaffected hemisphere to achieve this BCI control. To investigate this possibility, electroencephalographic (EEG) signals were recorded from four chronic hemispheric stroke patients as they performed (or attempted to perform) real and imagined hand tasks using either their affected or unaffected hand. Following performance of the screening task, the ability of patients to utilize a BCI system was investigated during on-line control of a one-dimensional control task. Significant ipsilateral motor signals (associated with movement intentions of the affected hand) in the unaffected hemisphere, which were found to be distinct from rest and contralateral signals, were identified and subsequently used for a simple online BCI control task. We demonstrate here for the first time that EEG signals from the unaffected hemisphere, associated with overt and
Nimmerjahn, Axel; Mukamel, Eran A.; Schnitzer, Mark J.
SUMMARY Although it is firmly established neuronal activity is a prime determinant of animal behavior, relationships between astrocytic excitation and animal behavior have remained opaque. Cerebellar Bergmann glia are radial astrocytes that are implicated in motor behavior and exhibit Ca2+-excitation. However, Ca2+-excitation in these cells has not previously been studied in behaving animals. Using two-photon microscopy we found that Bergmann glia exhibit three forms of Ca2+-excitation in awake behaving mice. Two of these are ongoing within the cerebellar vermis. During locomotor performance concerted Ca2+-excitation arises in networks of at least hundreds of Bergmann glia extending across several hundred microns or more. Concerted Ca2+-excitation was abolished by anesthesia or blockade of either neural activity or glutamatergic transmission. Thus, large networks of Bergmann glia can be activated by specific animal behaviors and undergo excitation of sufficient magnitude to potentially initiate macroscopic changes in brain dynamics or blood flow. PMID:19447095
Butler, Andrew J; James, Thomas W; James, Karin Harman
Everyday experience affords us many opportunities to learn about objects through multiple senses using physical interaction. Previous work has shown that active motor learning of unisensory items enhances memory and leads to the involvement of motor systems during subsequent perception. However, the impact of active motor learning on subsequent perception and recognition of associations among multiple senses has not been investigated. Twenty participants were included in an fMRI study that explored the impact of active motor learning on subsequent processing of unisensory and multisensory stimuli. Participants were exposed to visuo-motor associations between novel objects and novel sounds either through self-generated actions on the objects or by observing an experimenter produce the actions. Immediately after exposure, accuracy, RT, and BOLD fMRI measures were collected with unisensory and multisensory stimuli in associative perception and recognition tasks. Response times during audiovisual associative and unisensory recognition were enhanced by active learning, as was accuracy during audiovisual associative recognition. The difference in motor cortex activation between old and new associations was greater for the active than the passive group. Furthermore, functional connectivity between visual and motor cortices was stronger after active learning than passive learning. Active learning also led to greater activation of the fusiform gyrus during subsequent unisensory visual perception. Finally, brain regions implicated in audiovisual integration (e.g., STS) showed greater multisensory gain after active learning than after passive learning. Overall, the results show that active motor learning modulates the processing of multisensory associations.
Babikian, Sarine; Kanso, Eva; Kutch, Jason J
Human movement patterns have been shown to be particularly variable if many combinations of activity in different muscles all achieve the same task goal (i.e., are goal-equivalent). The nervous system appears to automatically vary its output among goal-equivalent combinations of muscle activity to minimize muscle fatigue or distribute tissue loading, but the neural mechanism of this "good" variation is unknown. Here we use a bimanual finger task, electroencephalography (EEG), and machine learning to determine if cortical signals can predict goal-equivalent variation in finger force output. 18 healthy participants applied left and right index finger forces to repeatedly perform a task that involved matching a total (sum of right and left) finger force. As in previous studies, we observed significantly more variability in goal-equivalent muscle activity across task repetitions compared to variability in muscle activity that would not achieve the goal: participants achieved the task in some repetitions with more right finger force and less left finger force (right > left) and in other repetitions with less right finger force and more left finger force (left > right). We found that EEG signals from the 500 milliseconds (ms) prior to each task repetition could make a significant prediction of which repetitions would have right > left and which would have left > right. We also found that cortical maps of sites contributing to the prediction contain both motor and pre-motor representation in the appropriate hemisphere. Thus, goal-equivalent variation in motor output may be implemented at a cortical level.
Glenberg, Arthur M; Sato, Marc; Cattaneo, Luigi; Riggio, Lucia; Palumbo, Daniele; Buccino, Giovanni
Embodiment theory proposes that neural systems for perception and action are also engaged during language comprehension. Previous neuroimaging and neurophysiological studies have only been able to demonstrate modulation of action systems during comprehension of concrete language. We provide neurophysiological evidence for modulation of motor system activity during the comprehension of both concrete and abstract language. In Experiment 1, when the described direction of object transfer or information transfer (e.g., away from the reader to another) matched the literal direction of a hand movement used to make a response, speed of responding was faster than when the two directions mismatched (an action-sentence compatibility effect). In Experiment 2, we used single-pulse transcranial magnetic stimulation to study changes in the corticospinal motor pathways to hand muscles while reading the same sentences. Relative to sentences that do not describe transfer, there is greater modulation of activity in the hand muscles when reading sentences describing transfer of both concrete objects and abstract information. These findings are discussed in relation to the human mirror neuron system.
Siemionow, V; Yue, G H; Ranganathan, V K; Liu, J Z; Sahgal, V
The purpose of this study was to investigate the relationship between EEG-derived motor activity-related cortical potential (MRCP) and voluntary muscle activation. Eight healthy volunteers participated in two experimental sessions. In one session, subjects performed isometric elbow-flexion contractions at four intensity levels [10%, 35%, 60%, and 85% maximal voluntary contraction (MVC)]. In another session, a given elbow-flexion force (35% MVC) was generated at three different rates (slow, intermediate, and fast). Thirty to 40 contractions were performed at each force level or rate. EEG signals were recorded from the scalp overlying the supplementary motor area (SMA) and contralateral sensorimotor cortex, and EMG signals were recorded from the skin surface overlying the belly of the biceps brachii and brachioradialis muscles during all contractions. In each trial, the force was used as the triggering signal for MRCP averaging. MRCP amplitude was measured from the beginning to the peak of the negative slope. The magnitude of MRCP from both EEG recording locations (sensorimotor cortex and SMA) was highly correlated with elbow-flexion force, rate of rising of force, and muscle EMG signals. These results suggest that MRCP represents cortical motor commands that scale the level of muscle activation.
Johann, Denis; Erlenkämper, Christoph; Kruse, Karsten
For biopolymers like cytoskeletal actin filaments and microtubules, assembly and disassembly are inherently dissipative processes. Molecular motors can affect the rates of subunit removal at filament ends. We introduce a driven lattice-gas model to study the effects of motor-induced depolymerization on the length of active biopolymers and find that increasing motor activity sharpens unimodal steady-state length distributions. Furthermore, for sufficiently fast moving motors, the relative width of the length distribution is determined only by the attachment rate of motors. Our results show how established molecular processes can be used to robustly regulate the size of cytoskeletal structures like mitotic spindles.
Hong, Keum-Shik; Naseer, Noman; Kim, Yun-Hee
Functional near-infrared spectroscopy (fNIRS) is an optical imaging method that can be used for a brain-computer interface (BCI). In the present study, we concurrently measure and discriminate fNIRS signals evoked by three different mental activities, that is, mental arithmetic (MA), right-hand motor imagery (RI), and left-hand motor imagery (LI). Ten healthy subjects were asked to perform the MA, RI, and LI during a 10s task period. Using a continuous-wave NIRS system, signals were acquired concurrently from the prefrontal and the primary motor cortices. Multiclass linear discriminant analysis was utilized to classify MA vs. RI vs. LI with an average classification accuracy of 75.6% across the ten subjects, for a 2-7s time window during the a 10s task period. These results demonstrate the feasibility of implementing a three-class fNIRS-BCI using three different intentionally-generated cognitive tasks as inputs.
Taquahashi, Y; Yonezawa, K; Nishimura, M
We investigated the effects of motor activities on transmitter release in mouse nerve-muscle preparations of the diaphragm muscle (DPH), extensor digitorum longus muscle (EDL), and soleus muscle (SOL). Mice were divided into a control group, a motor-restricted (RST) group, and a motor-compelled (CMP) group. The quantal content (m) of endplate potentials was measured intracellularly. In DPH the motor activity was unaffected. In the CMP group the m value of the EDL group increased with increases in the cooperativity of Ca2+ in transmitter release. Compared with the CMP group, the SOL of the RST group had a smaller m value with increases in the cooperativity of Ca2+ in transmitter release. These results suggest that motor activities can influence neuromuscular activity specific to different systems, however, the motor compulsion specifically activated the function of EDL and the motor restriction activated the function of SOL, and these effects might lead to altered activity of the release of transmitter quanta in motor nerve terminals of mice.
Suzuki, Tomotaka; Higashi, Toshio; Takagi, Mineko; Sugawara, Kenichi
In this study, we investigated how ipsilateral motor cortex (M1) activation during unimanual hand movements and hemispheric asymmetry changed after motor skill learning. Eleven right-handed participants preformed a two-ball-rotation motor task with the right and the left hand, separately, in all experimental sessions. Before and after exercise sessions, the degree of ipsilateral M1 activation during brief execution of the motor task was measured as changes in the size of motor-evoked potentials (MEPs) of the thenar and the first dorsal interosseous muscle of the nontask hand using transcranial magnetic stimulation. Before exercise, MEPs of the nontask hand were significantly facilitated on both sides during the motor task. After exercise, facilitation of MEPs of the nontask hand during the motor task was significantly reduced for the right hand (thenar: P=0.014, first dorsal interosseous: P=0.022) but not for the left hand. We conclude that ipsilateral M1 activation, associated with a complex motor task, is first symmetrical in both hemispheres. However, on exercise, ipsilateral activation is reduced only in left M1, indicating a stronger learning-dependent modification of motor networks within the left hemisphere.
Quistberg, D Alex; Koepsell, Thomas D; Boyle, Linda Ng; Miranda, J Jaime; Johnston, Brian D; Ebel, Beth E
Safe walking environments are essential for protecting pedestrians and promoting physical activity. In Peru, pedestrians comprise over three-quarters of road fatality victims. Pedestrian signalization plays an important role managing pedestrian and vehicle traffic and may help improve pedestrian safety. We examined the relationship between pedestrian-motor vehicle collisions and the presence of visible traffic signals, pedestrian signals, and signal timing to determine whether these countermeasures improved pedestrian safety. A matched case-control design was used where the units of study were crossing locations. We randomly sampled 97 control-matched collisions (weighted N=1134) at intersections occurring from October, 2010 to January, 2011 in Lima. Each case-control pair was matched on proximity, street classification, and number of lanes. Sites were visited between February, 2011 and September, 2011. Each analysis accounted for sampling weight and matching and was adjusted for vehicle and pedestrian traffic flow, crossing width, and mean vehicle speed. Collisions were more common where a phased pedestrian signal (green or red-light signal) was present compared to no signalization (odds ratio [OR] 8.88, 95% Confidence Interval [CI] 1.32-59.6). A longer pedestrian-specific signal duration was associated with collision risk (OR 5.31, 95% CI 1.02-9.60 per 15-s interval). Collisions occurred more commonly in the presence of any signalization visible to pedestrians or pedestrian-specific signalization, though these associations were not statistically significant. Signalization efforts were not associated with lower risk for pedestrians; rather, they were associated with an increased risk of pedestrian-vehicle collisions.
Quistberg, D. Alex; Koepsell, Thomas D.; Boyle, Linda Ng; Miranda, J. Jaime; Johnston, Brian D.; Ebel, Beth E.
Safe walking environments are essential for protecting pedestrians and promoting physical activity. In Peru, pedestrians comprise of over three-quarters of road fatality victims. Pedestrian signalization plays an important role managing pedestrian and vehicle traffic and may help improve pedestrian safety. We examined the relationship between pedestrian-motor vehicle collisions and the presence of visible traffic signals, pedestrian signals, and signal timing to determine whether these countermeasures improved pedestrian safety. A matched case-control design was used where the units of study were crossing locations. We randomly sampled 97 control-matched collisions (weighted N=1134) at intersections occurring from October, 2010 to January, 2011 in Lima. Each case-control pair was matched on proximity, street classification, and number of lanes. Sites were visited between February, 2011 and September, 2011. Each analysis accounted for sampling weight and matching and was adjusted for vehicle and pedestrian traffic flow, crossing width, and mean vehicle speed. Collisions were more common where a phased pedestrian signal (green or red-lit signal) was present compared to no signalization (odds ratio [OR] 8.88, 95% Confidence Interval [CI] 1.32–59.6). A longer pedestrian-specific signal duration was associated with collision risk (OR 5.31, 95% CI 1.02–9.60 per 15-second interval). Collisions occurred more commonly in the presence of any signalization visible to pedestrians or pedestrian-specific signalization, though these associations were not statistically significant. Signalization efforts were not associated with lower risk for pedestrians; rather, they were associated with an increased risk of pedestrian-vehicle collisions. PMID:24821630
Lawton, Kristy J; Perry, Wick M; Yamaguchi, Ayako; Zornik, Erik
Central patterns generators (CPGs) are neural circuits that drive rhythmic motor output without sensory feedback. Vertebrate CPGs are generally believed to operate in a top-down manner in which premotor interneurons activate motor neurons that in turn drive muscles. In contrast, the frog (Xenopus laevis) vocal CPG contains a functionally unexplored neuronal projection from the motor nucleus to the premotor nucleus, indicating a recurrent pathway that may contribute to rhythm generation. In this study, we characterized the function of this bottom-up connection. The X. laevis vocal CPG produces a 50-60 Hz "fast trill" song used by males during courtship. We recorded "fictive vocalizations" in the in vitro CPG from the laryngeal nerve while simultaneously recording premotor activity at the population and single-cell level. We show that transecting the motor-to-premotor projection eliminated the characteristic firing rate of premotor neurons. Silencing motor neurons with the intracellular sodium channel blocker QX-314 also disrupted premotor rhythms, as did blockade of nicotinic synapses in the motor nucleus (the putative location of motor neuron-to-interneuron connections). Electrically stimulating the laryngeal nerve elicited primarily IPSPs in premotor neurons that could be blocked by a nicotinic receptor antagonist. Our results indicate that an inhibitory signal, activated by motor neurons, is required for proper CPG function. To our knowledge, these findings represent the first example of a CPG in which precise premotor rhythms are tuned by motor neuron activity.SIGNIFICANCE STATEMENT Central pattern generators (CPGs) are neural circuits that produce rhythmic behaviors. In vertebrates, motor neurons are not commonly known to contribute to CPG function, with the exception of a few spinal circuits where the functional significance of motor neuron feedback is still poorly understood. The frog hindbrain vocal circuit contains a previously unexplored connection from
Packard, D. T.
A control system for a brushless DC motor responsive to digital control signals is disclosed. The motor includes a multiphase wound stator and a permanent magnet rotor. The motor is arranged so that each phase winding, when energized from a DC source, will drive the rotor through a predetermined angular position or step. A commutation signal generator responsive to the shaft position provides a commutation signal for each winding. A programmable control signal generator such as a computer or microprocessor produces individual digital control signals for each phase winding. The control signals and commutation signals associated with each winding are applied to an AND gate for that phase winding. Each gate controls a switch connected in series with the associated phase winding and the DC source so that each phase winding is energized only when the commutation signal and the control signal associated with that phase winding are present. The motor shaft may be advanced one step at a time to a desired position by applying a predetermined number of control signals in the proper sequence to the AND gates and the torque generated by the motor be regulated by applying a separate control signal and each AND gate which is pulse width modulated to control the total time that each switch connects its associated winding to the DC source during each commutation period.
Packard, D. T. (Inventor)
A control system for a brushless DC motor responsive to digital control signals is disclosed. The motor includes a multiphase wound stator and a permanent magnet rotor. The motor is arranged so that each phase winding, when energized from a DC source, will drive the rotor through a predetermined angular position or step. A commutation signal generator responsive to the shaft position provides a commutation signal for each winding. A programmable control signal generator such as a computer or microprocessor produces individual digital control signals for each phase winding. The control signals and commutation signals associated with each winding are applied to an AND gate for that phase winding. Each gate controls a switch connected in series with the associated phase winding and the DC source so that each phase winding is energized only when the commutation signal and the control signal associated with that phase winding are present. The motor shaft may be advanced one step at a time to a desired position by applying a predetermined number of control signals in the proper sequence to the AND gates and the torque generated by the motor be regulated by applying a separate control signal and each AND gate which is pulse width modulated to control the total time that each switch connects its associated winding to the DC source during each commutation period.
Patel, Jyoti C; Rossignol, Elsa; Rice, Margaret E; Machold, Robert P
Dopamine transmission is critical for exploratory motor behaviour. A key regulator is acetylcholine; forebrain acetylcholine regulates striatal dopamine release, whereas brainstem cholinergic inputs regulate the transition of dopamine neurons from tonic to burst firing modes. How these sources of cholinergic activity combine to control dopamine efflux and exploratory motor behaviour is unclear. Here we show that mice lacking total forebrain acetylcholine exhibit enhanced frequency-dependent striatal dopamine release and are hyperactive in a novel environment, whereas mice lacking rostral brainstem acetylcholine are hypoactive. Exploratory motor behaviour is normalized by the removal of both cholinergic sources. Involvement of dopamine in the exploratory motor phenotypes observed in these mutants is indicated by their altered sensitivity to the dopamine D2 receptor antagonist raclopride. These results support a model in which forebrain and brainstem cholinergic systems act in tandem to regulate striatal dopamine signalling for proper control of motor activity.
Maity, Biswanath; Stewart, Adele; Yang, Jianqi; Loo, Lipin; Sheff, David; Shepherd, Andrew J.; Mohapatra, Durga P.; Fisher, Rory A.
γ-Aminobutyric acid (GABA) release from inhibitory interneurons located within the cerebellar cortex limits the extent of neuronal excitation in part through activation of metabotropic GABAB receptors. Stimulation of these receptors triggers a number of downstream signaling events, including activation of GIRK channels by the Gβγ dimer resulting in membrane hyperpolarization and inhibition of neurotransmitter release from presynaptic sites. Here, we identify RGS6, a member of the R7 subfamily of RGS proteins, as a key regulator of GABABR signaling in cerebellum. RGS6 is enriched in the granule cell layer of the cerebellum along with neuronal GIRK channel subunits 1 and 2 where RGS6 forms a complex with known binding partners Gβ5 and R7BP. Mice lacking RGS6 exhibit abnormal gait and ataxia characterized by impaired rotarod performance improved by treatment with a GABABR antagonist. RGS6−/− mice administered baclofen also showed exaggerated motor coordination deficits compared with their wild-type counterparts. Isolated cerebellar neurons natively expressed RGS6, GABABR, and GIRK channel subunits, and cerebellar granule neurons from RGS6−/− mice showed a significant delay in the deactivation kinetics of baclofen-induced GIRK channel currents. These results establish RGS6 as a key component of GABABR signaling and represent the first demonstration of an essential role for modulatory actions of RGS proteins in adult cerebellum. Dysregulation of RGS6 expression in human patients could potentially contribute to loss of motor coordination and, thus, pharmacological manipulation of RGS6 levels might represent a viable means to treat patients with ataxias of cerebellar origin. PMID:22179605
Papazachariadis, Odysseas; Dante, Vittorio; Ferraina, Stefano
Aiming to better define the functional influence of somatosensory stimuli on the primary motor cortex (M1) of primates, we investigated changes in extracellular neural activity induced by repetitive median nerve stimulation (MNS). We described neural adaptation and signal integration in both the multiunit activity (MUA) and the local field potential (LFP). To identify integration of initial M1 activity in the MNS response, we tested the correlation between peak amplitude responses and band energy preceding the peaks. Most of the sites studied in the M1 resulted responsive to MNS. MUA response peak amplitude decreased significantly in time in all sites during repetitive MNS, LFP response peak amplitude instead resulted more variable. Similarly, correlation analysis with the initial activity revealed a significant influence when tested using MUA peak amplitude modulation and a less significant correlation when tested using LFP peak amplitude. Our findings improve current knowledge on mechanisms underlying early M1 changes consequent to afferent somatosensory stimuli.
Borgmann, Anke; Toth, Tibor I; Gruhn, Matthias; Daun-Gruhn, Silvia; Büschges, Ansgar
Legged locomotion requires that information local to one leg, and inter-segmental signals coming from the other legs are processed appropriately to establish a coordinated walking pattern.However, very little is known about the relative importance of local and inter-segmental signals when they converge upon the central pattern generators (CPGs) of different leg joints.We investigated this question on the CPG of the middle leg coxa–trochanter (CTr)-joint of the stick insect which is responsible for lifting and lowering the leg.We used a semi-intact preparation with an intact front leg stepping on a treadmill, and simultaneously stimulated load sensors of the middle leg.We found that middle leg load signals induce bursts in the middle leg depressor motoneurons(MNs). The same local load signals could also elicit rhythmic activity in the CPG of the middle leg CTr-joint when the stimulation of middle leg load sensors coincided with front leg stepping. However, the influence of front leg stepping was generally weak such that front leg stepping alone was only rarely accompanied by switching between middle leg levator and depressor MN activity. We therefore conclude that the impact of the local sensory signals on the levator–depressor motor system is stronger than the inter-segmental influence through front leg stepping.
de Iorio, F; Malagelada, C; Azpiroz, F; Maluenda, M; Violanti, C; Igual, L; Vitrià, J; Malagelada, J-R
A programme for evaluation of intestinal motility has been recently developed based on endoluminal image analysis using computer vision methodology and machine learning techniques. Our aim was to determine the effect of intestinal muscle inhibition on wall motion, dynamics of luminal content and transit in the small bowel. Fourteen healthy subjects ingested the endoscopic capsule (Pillcam, Given Imaging) in fasting conditions. Seven of them received glucagon (4.8 microg kg(-1) bolus followed by a 9.6 microg kg(-1) h(-1) infusion during 1 h) and in the other seven, fasting activity was recorded, as controls. This dose of glucagon has previously shown to inhibit both tonic and phasic intestinal motor activity. Endoluminal image and displacement was analyzed by means of a computer vision programme specifically developed for the evaluation of muscular activity (contractile and non-contractile patterns), intestinal contents, endoluminal motion and transit. Thirty-minute periods before, during and after glucagon infusion were analyzed and compared with equivalent periods in controls. No differences were found in the parameters measured during the baseline (pretest) periods when comparing glucagon and control experiments. During glucagon infusion, there was a significant reduction in contractile activity (0.2 +/- 0.1 vs 4.2 +/- 0.9 luminal closures per min, P < 0.05; 0.4 +/- 0.1 vs 3.4 +/- 1.2% of images with radial wrinkles, P < 0.05) and a significant reduction of endoluminal motion (82 +/- 9 vs 21 +/- 10% of static images, P < 0.05). Endoluminal image analysis, by means of computer vision and machine learning techniques, can reliably detect reduced intestinal muscle activity and motion.
Poliak, Sebastian; Morales, Daniel; Croteau, Louis-Philippe; Krawchuk, Dayana; Palmesino, Elena; Morton, Susan; Cloutier, Jean-François; Charron, Frederic; Dalva, Matthew B; Ackerman, Susan L; Kao, Tzu-Jen; Kania, Artur
During neural circuit assembly, axonal growth cones are exposed to multiple guidance signals at trajectory choice points. While axonal responses to individual guidance cues have been extensively studied, less is known about responses to combination of signals and underlying molecular mechanisms. Here, we studied the convergence of signals directing trajectory selection of spinal motor axons entering the limb. We first demonstrate that Netrin-1 attracts and repels distinct motor axon populations, according to their expression of Netrin receptors. Quantitative in vitro assays demonstrate that motor axons synergistically integrate both attractive or repulsive Netrin-1 signals together with repulsive ephrin signals. Our investigations of the mechanism of ephrin-B2 and Netrin-1 integration demonstrate that the Netrin receptor Unc5c and the ephrin receptor EphB2 can form a complex in a ligand-dependent manner and that Netrin-ephrin synergistic growth cones responses involve the potentiation of Src family kinase signaling, a common effector of both pathways.
Giovannucci, Andrea; Badura, Aleksandra; Deverett, Ben; Najafi, Farzaneh; Pereira, Talmo D; Gao, Zhenyu; Ozden, Ilker; Kloth, Alexander D; Pnevmatikakis, Eftychios; Paninski, Liam; De Zeeuw, Chris I; Medina, Javier F; Wang, Samuel S-H
Cerebellar granule cells, which constitute half the brain's neurons, supply Purkinje cells with contextual information necessary for motor learning, but how they encode this information is unknown. Here we show, using two-photon microscopy to track neural activity over multiple days of cerebellum-dependent eyeblink conditioning in mice, that granule cell populations acquire a dense representation of the anticipatory eyelid movement. Initially, granule cells responded to neutral visual and somatosensory stimuli as well as periorbital airpuffs used for training. As learning progressed, two-thirds of monitored granule cells acquired a conditional response whose timing matched or preceded the learned eyelid movements. Granule cell activity covaried trial by trial to form a redundant code. Many granule cells were also active during movements of nearby body structures. Thus, a predictive signal about the upcoming movement is widely available at the input stage of the cerebellar cortex, as required by forward models of cerebellar control.
Packard, Douglas T. (Inventor); Schmitt, Donald E. (Inventor)
A control system for a brushless DC motor responsive to digital control signals is disclosed. The motor includes a multiphase wound stator and a permanent magnet rotor. The rotor is arranged so that each phase winding, when energized from a DC source, will drive the rotor through a predetermined angular position or step. A commutation signal generator responsive to the shaft position provides a commutation signal for each winding. A programmable control signal generator such as a computer or microprocessor produces individual digital control signals for each phase winding. The control signals and commutation signals associated with each winding are applied to an AND gate for that phase winding. Each gate controls a switch connected in series with the associated phase winding and the DC source so that each phase winding is energized only when the commutation signal and the control signal associated with that phase winding are present. The motor shaft may be advanced one step at a time to a desired position by applying a predetermined number of control signals in the proper sequence to the AND gates and the torque generated by the motor may be regulated by applying a separate control signal to each AND gate which is pulse width modulated to control the total time that each switch connects its associated winding to the DC source during each commutation period.
Luu, Billy L; Inglis, J Timothy; Huryn, Thomas P; Van der Loos, H F Machiel; Croft, Elizabeth A; Blouin, Jean-Sébastien
We investigate whether the muscle response evoked by an electrically induced vestibular perturbation during standing is related to congruent sensory and motor signals. A robotic platform that simulated the mechanics of a standing person was used to manipulate the relationship between the action of the calf muscles and the movement of the body. Subjects braced on top of the platform with the ankles sway referenced to its motion were required to balance its simulated body-like load by modulating ankle plantar-flexor torque. Here, afferent signals of body motion were congruent with the motor command to the calf muscles to balance the body. Stochastic vestibular stimulation (±4 mA, 0–25 Hz) applied during this task evoked a biphasic response in both soleus muscles that was similar to the response observed during standing for all subjects. When the body was rotated through the same motion experienced during the balancing task, a small muscle response was observed in only the right soleus and in only half of the subjects. However, the timing and shape of this response did not resemble the vestibular-evoked response obtained during standing. When the balancing task was interspersed with periods of computer-controlled platform rotations that emulated the balancing motion so that subjects thought that they were constantly balancing the platform, coherence between the input vestibular stimulus and soleus electromyogram activity decreased significantly (P < 0.05) during the period when plantar-flexor activity did not affect the motion of the body. The decrease in coherence occurred at 175 ms after the transition to computer-controlled motion, which subjects did not detect until after 2247 ms (Confidence Interval 1801, 2693), and then only half of the time. Our results indicate that the response to an electrically induced vestibular perturbation is organised in the absence of conscious perception when sensory feedback is congruent with the underlying motor behaviour. PMID
Wright, David J.; Holmes, Paul; Di Russo, Francesco; Loporto, Michela; Smith, Dave
Experts in a skill produce movement-related cortical potentials (MRCPs) of smaller amplitude and later onset than novices. This may indicate that, following long-term training, experts require less effort to plan motor skill performance. However, no longitudinal evidence exists to support this claim. To address this, EEG was used to study the effect of motor skill training on cortical activity related to motor planning. Ten non-musicians took part in a 5-week training study learning to play guitar. At week 1, the MRCP was recorded from motor areas whilst participants played the G Major scale. Following a period of practice of the scale, the MRCP was recorded again at week 5. Results showed that the amplitude of the later pre-movement components were smaller at week 5 compared to week 1. This may indicate that, following training, less activity at motor cortex sites is involved in motor skill preparation. This supports claims for a more efficient motor preparation following motor skill training. PMID:23251647
Gueugneau, Nicolas; Schweighofer, Nicolas; Papaxanthis, Charalambos
Motor prediction, i.e., the ability to predict the sensory consequences of motor commands, is critical for adapted motor behavior. Like speed or force, the accuracy of motor prediction varies in a 24-hour basis. Although the prevailing view is that basic biological markers regulate this circadian modulation, behavioral factors such as physical activity, itself modulated by the alternation of night and day, can also regulate motor prediction. Here, we propose that physical activity updates motor prediction on a daily basis. We tested our hypothesis by up- and down-regulating physical activity via arm-immobilization and high-intensity training, respectively. Motor prediction was assessed by measuring the timing differences between actual and mental arm movements. Results show that although mental movement time was modulated during the day when the arm was unconstrained, it remained constant when the arm was immobilized. Additionally, increase of physical activity, via release from immobilization or intense bout of training, significantly reduced mental movement time. Finally, mental and actual times were similar in the afternoon in the unconstrained condition, indicating that predicted and actual movements match after sufficient amount of physical activity. Our study supports the view that physical activity calibrates motor predictions on a daily basis.
... Transportation, Federal Motor Carrier Safety Administration, 1200 New Jersey Avenue SE., Washington, DC, 20590... Federal Motor Carrier Safety Administration Agency Information Collection Activities; New Information Collection Request: Commercial Motor Vehicle Marking Requirements AGENCY: Federal Motor Carrier...
... Federal Motor Carrier Safety Administration Agency Information Collection Activities; New Information Collection: Commercial Motor Vehicle Marking Requirements AGENCY: Federal Motor Carrier Safety Administration... require marking of vehicles and intermodal equipment by motor carriers, freight forwarders and...
This dissertation reports findings centered principally on comprehensive research related to human bio-signals (EEG, MEG, EMG and fMRI) acquired during repetitive maximal voluntary contractions (MVC) that induced severe fatigue. Fatigue is a common experience that reduces productivity and quality of life and increases chances of injury. Although abundant information has been gained in the last several decades regarding muscular and spinal-level mechanisms of muscle fatigue, very little is known about how cortical centers control and respond to fatigue. The main purpose of this study was to examine the fatigue effects on the central nervous system by analyzing the bio-signals collected in the designed experiments. Healthy human subjects were asked to perform a series of repetitive handgrip MVCs with their dominant hand until exhaustion. Handgrip forces, electrical activity (EMG) from primary and non-primary muscles, and EEG, MEG, or fMRI signals from different locations of the brain were recorded simultaneously. The time series data were segmented into several physiologically meaningful epochs (time phases), from rest to preparation to movement execution/sustaining. A series of studies, including motor-related cortical potential (MRCP) analysis, power spectrum analysis, time-frequency (spectrogram) analysis of EEG, EEG source localization and nonlinear analysis (fractal dimension and largest Lyapunov exponent), and fMRI analysis, was applied to the data. We hypothesized that the fatigue effects would act differently on brain signals of different phases. The MRCP results showed that the negative potential (NP) related to motor task preparation only had minimal changes with fatigue. The power of all EEG frequencies did not alter significantly during the preparation phase but decreased significantly during the sustained phase of the contraction. The fractal dimension and the largest Lyapunov exponent decreased significantly during the sustained phase as fatigue
Our group has developed a family of single molecules termed nanocars, which are aimed at performing controllable motion on surfaces. In this work, a series of light-activated motorized nanomachines incorporated with a MHz frequency light-activated unidirectional rotary motor were designed and synthesized. We hope the light-activated motor can serve as the powering unit for the nanomachines, and perform controllable translational motion on surfaces or in solution. A series of motorized nanovehicles intended for scanning tunneling microscopy (STM) imaging were designed and synthesized. A p-carborane-wheeled motorized nanocar was synthesized and monitored by STM. Single-molecule imaging was accomplished on a Cu(111) surface. However, further manipulations did lead to motor induced lateral motion. We attributed this result to the strong molecule-surface interactions between the p-carborane-wheeled nanocar and the Cu(111) surface and possible energy transfer between the rotary motor and the Cu(111) surface. To fine-tune the molecule-surface interactions, an adamantane-wheeled motorized nanocar and a three-wheel nanoroadster were designed and synthesized. In addition, the STM substrates will be varied and different combinations of molecule-surface interactions will be studied. As a complimentary imaging method to STM, single-molecule fluorescence microscopy (SMFM) also provides single-molecule level resolution. Unlike STM experiment requires ultra-high vacuum and conductive substrate, SMFM experiment is conducted at ambient conditions and uses non-conductive substrate. This imaging method allows us to study another category of molecule-surface interactions. We plan to design a fluorescent motorized nanocar that is suitable for SMFM studies. However, both the motor and fluorophore are photochemically active molecules. In proximity, some undesired energy transfer or interference could occur. A cyanine 5- (cy5-) tagged motorized nanocar incorporated with the MHz motor was
Sorrell, Howard M.
A circuit approach and station techniques are used to depict perceptual motor games for handicapped and nonhandicapped children. Twenty activities are described in terms of objectives, materials, and procedures, and their focus on visual tracking, visual discrimination and copying of forms, spatial body perception, fine motor coordination, tactile…
Cho, Woosang; Vidaurre, Carmen; Hoffmann, Ulrich; Birbaumer, Niels; Ramos-Murguialday, Ander
Stroke is a cardiovascular accident within the brain resulting in motor and sensory impairment in most of the survivors. A stroke can produce complete paralysis of the limb although sensory abilities are normally preserved. Functional electrical stimulation (FES), robotics and brain computer interfaces (BCIs) have been used to induce motor rehabilitation. In this work we measured the brain activity of healthy volunteers using electroencephalography (EEG) during FES, passive movements, active movements, motor imagery of the hand and resting to compare afferent and efferent brain signals produced during these motor related activities and to define possible features for an online FES-BCI. In the conditions in which the hand was moved we limited the movement range in order to control the afferent flow. Although we observed that there is a subject dependent frequency and spatial distribution of efferent and afferent signals, common patterns between conditions and subjects were present mainly in the low beta frequency range. When averaging all the subjects together the most significant frequency bin comparing each condition versus rest was exactly the same for all conditions but motor imagery. These results suggest that to implement an on-line FES-BCI, afferent brain signals resulting from FES have to be filtered and time-frequency-spatial features need to be used.
Rutkowsky, Jennifer M; Knotts, Trina A; Ono-Moore, Kikumi D; McCoin, Colin S; Huang, Shurong; Schneider, Dina; Singh, Shamsher; Adams, Sean H; Hwang, Daniel H
Incomplete β-oxidation of fatty acids in mitochondria is a feature of insulin resistance and type 2 diabetes mellitus (T2DM). Previous studies revealed that plasma concentrations of medium- and long-chain acylcarnitines (by-products of incomplete β-oxidation) are elevated in T2DM and insulin resistance. In a previous study, we reported that mixed D,L isomers of C12- or C14-carnitine induced an NF-κB-luciferase reporter gene in RAW 264.7 cells, suggesting potential activation of proinflammatory pathways. Here, we determined whether the physiologically relevant L-acylcarnitines activate classical proinflammatory signaling pathways and if these outcomes involve pattern recognition receptor (PRR)-associated pathways. Acylcarnitines induced the expression of cyclooxygenase-2 in a chain length-dependent manner in RAW 264.7 cells. L-C14 carnitine (5-25 μM), used as a representative acylcarnitine, stimulated the expression and secretion of proinflammatory cytokines in a dose-dependent manner. Furthermore, L-C14 carnitine induced phosphorylation of JNK and ERK, common downstream components of many proinflammatory signaling pathways including PRRs. Knockdown of MyD88, a key cofactor in PRR signaling and inflammation, blunted the proinflammatory effects of acylcarnitine. While these results point to potential involvement of PRRs, L-C14 carnitine promoted IL-8 secretion from human epithelial cells (HCT-116) lacking Toll-like receptors (TLR)2 and -4, and did not activate reporter constructs in TLR overexpression cell models. Thus, acylcarnitines have the potential to activate inflammation, but the specific molecular and tissue target(s) involved remain to be identified.
Rutkowsky, Jennifer M.; Knotts, Trina A.; Ono-Moore, Kikumi D.; McCoin, Colin S.; Huang, Shurong; Schneider, Dina; Singh, Shamsher; Hwang, Daniel H.
Incomplete β-oxidation of fatty acids in mitochondria is a feature of insulin resistance and type 2 diabetes mellitus (T2DM). Previous studies revealed that plasma concentrations of medium- and long-chain acylcarnitines (by-products of incomplete β-oxidation) are elevated in T2DM and insulin resistance. In a previous study, we reported that mixed d,l isomers of C12- or C14-carnitine induced an NF-κB-luciferase reporter gene in RAW 264.7 cells, suggesting potential activation of proinflammatory pathways. Here, we determined whether the physiologically relevant l-acylcarnitines activate classical proinflammatory signaling pathways and if these outcomes involve pattern recognition receptor (PRR)-associated pathways. Acylcarnitines induced the expression of cyclooxygenase-2 in a chain length-dependent manner in RAW 264.7 cells. l-C14 carnitine (5–25 μM), used as a representative acylcarnitine, stimulated the expression and secretion of proinflammatory cytokines in a dose-dependent manner. Furthermore, l-C14 carnitine induced phosphorylation of JNK and ERK, common downstream components of many proinflammatory signaling pathways including PRRs. Knockdown of MyD88, a key cofactor in PRR signaling and inflammation, blunted the proinflammatory effects of acylcarnitine. While these results point to potential involvement of PRRs, l-C14 carnitine promoted IL-8 secretion from human epithelial cells (HCT-116) lacking Toll-like receptors (TLR)2 and -4, and did not activate reporter constructs in TLR overexpression cell models. Thus, acylcarnitines have the potential to activate inflammation, but the specific molecular and tissue target(s) involved remain to be identified. PMID:24760988
Ranganathan, Rajiv; Krishnan, Chandramouli; Dhaher, Yasin Y; Rymer, William Z
The motor module hypothesis in motor control proposes that the nervous system can simplify the problem of controlling a large number of muscles in human movement by grouping muscles into a smaller number of modules. Here, we tested one prediction of the modular organization hypothesis by examining whether there is preferential exploration along these motor modules during the learning of a new gait pattern. Healthy college-aged participants learned a new gait pattern which required increased hip and knee flexion during the swing phase while walking in a lower-extremity robot (Lokomat). The new gait pattern was displayed as a foot trajectory in the sagittal plane and participants attempted to match their foot trajectory to this template. We recorded EMG from 8 lower-extremity muscles and we extracted motor modules during both baseline walking and target-tracking using non-negative matrix factorization (NMF). Results showed increased trajectory variability in the first block of learning, indicating that participants were engaged in exploratory behavior. Critically, when we examined the muscle activity during this exploratory phase, we found that the composition of motor modules changed significantly within the first few strides of attempting the new gait pattern. The lack of persistence of the motor modules under even short time scales suggests that motor modules extracted during locomotion may be more indicative of correlated muscle activity induced by the task constraints of walking, rather than reflecting a modular control strategy.
Fry, Amanda L; Laboy, Jocelyn T; Norman, Kenneth R
The complex molecular and cellular mechanisms underlying neuronal control of animal movement are not well understood. Locomotion of Caenorhabditis elegans is mediated by a neuronal circuit that produces coordinated sinusoidal movement. Here we utilize this simple, yet elegant, behaviour to show that VAV-1, a conserved guanine nucleotide exchange factor for Rho-family GTPases, negatively regulates motor circuit activity and the rate of locomotion. While vav-1 is expressed in a small subset of neurons, we find that VAV-1 function is required in a single interneuron, ALA, to regulate motor neuron circuit activity. Furthermore, we show by genetic and optogenetic manipulation of ALA that VAV-1 is required for the excitation and activation of this neuron. We find that ALA signalling inhibits command interneuron activity by abrogating excitatory signalling in the command interneurons, which is responsible for promoting motor neuron circuit activity. Together, our data describe a novel neuromodulatory role for VAV-1-dependent signalling in the regulation of motor circuit activity and locomotion.
Turner, Clare E; Byblow, Winston D; Stinear, Cathy M; Gant, Nicholas
The presence of carbohydrate in the human mouth has been associated with the facilitation of motor output and improvements in physical performance. Oral receptors have been identified as a potential mode of afferent transduction for this novel form of nutrient signalling that is distinct from taste. In the current study oral exposure to carbohydrate was combined with a motor task in a neuroimaging environment to identify areas of the brain involved in this phenomenon. A mouth-rinsing protocol was conducted whilst carbohydrate (CHO) and taste-matched placebo (PLA) solutions were delivered and recovered from the mouths of 10 healthy volunteers within a double-blind, counterbalanced design. This protocol eliminates post-oral factors and controls for the perceptual qualities of solutions. Functional magnetic resonance imaging of the brain was used to identify cortical areas responsive to oral carbohydrate during rest and activity phases of a hand-grip motor task. Mean blood-oxygen-level dependent signal change experienced in the contralateral primary sensorimotor cortex was larger for CHO compared with PLA during the motor task when contrasted with a control condition. Areas of activation associated with CHO exclusively were observed over the primary taste cortex and regions involved in visual perception. Regions in the limbic system associated with reward were also significantly more active with CHO. This is the first demonstration that oral carbohydrate signalling can increase activation within the primary sensorimotor cortex during physical activity and enhance activation of neural networks involved in sensory perception.
Williams, Preston T.J.A.
The corticospinal and rubrospinal systems function in skilled movement control. A key question is how do these systems develop the capacity to coordinate their motor functions and, in turn, if the red nucleus/rubrospinal tract (RN/RST) compensates for developmental corticospinal injury? We used the cat to investigate whether the developing rubrospinal system is shaped by activity-dependent interactions with the developing corticospinal system. We unilaterally inactivated M1 by muscimol microinfusion between postnatal weeks 5 and 7 to examine activity-dependent interactions and whether the RN/RST compensates for corticospinal tract (CST) developmental motor impairments and CST misprojections after M1 inactivation. We examined the RN motor map and RST cervical projections at 7 weeks of age, while the corticospinal system was inactivated, and at 14 weeks, after activity returned. During M1 inactivation, the RN on the same side showed normal RST projections and reduced motor thresholds, suggestive of precocious development. By contrast, the RN on the untreated/active M1 side showed sparse RST projections and an immature motor map. After M1 activity returned later in adolescent cat development, RN on the active M1/CST side continued to show a substantial loss of spinal terminations and an impaired motor map. RN/RST on the inactivated side regressed to a smaller map and fewer axons. Our findings suggest that the developing rubrospinal system is under activity-dependent regulation by the corticospinal system for establishing mature RST connections and RN motor map. The lack of RS compensation on the non-inactivated side can be explained by development of ipsilateral misprojections from the active M1 that outcompete the RST. SIGNIFICANCE STATEMENT Skilled movements reflect the activity of multiple descending motor systems and their interactions with spinal motor circuits. Currently, there is little insight into whether motor systems interact during development to
Fargier, Raphaël; Paulignan, Yves; Boulenger, Véronique; Monaghan, Padraic; Reboul, Anne; Nazir, Tatjana A
Action words referring to face, arm or leg actions activate areas along the motor strip that also control the planning and execution of the actions specified by the words. This electroencephalogram (EEG) study aimed to test the learning profile of this language-induced motor activity. Participants were trained to associate novel verbal stimuli to videos of object-oriented hand and arm movements or animated visual images on two consecutive days. Each training session was preceded and followed by a test-session with isolated videos and verbal stimuli. We measured motor-related brain activity (reflected by a desynchronization in the μ frequency bands; 8-12 Hz range) localized at centro-parietal and fronto-central electrodes. We compared activity from viewing the videos to activity resulting from processing the language stimuli only. At centro-parietal electrodes, stable action-related μ suppression was observed during viewing of videos in each test-session of the two days. For processing of verbal stimuli associated with motor actions, a similar pattern of activity was evident only in the second test-session of Day 1. Over the fronto-central regions, μ suppression was observed in the second test-session of Day 2 for the videos and in the second test-session of Day 1 for the verbal stimuli. Whereas the centro-parietal μ suppression can be attributed to motor events actually experienced during training, the fronto-central μ suppression seems to serve as a convergence zone that mediates underspecified motor information. Consequently, sensory-motor reactivations through which concepts are comprehended seem to differ in neural dynamics from those implicated in their acquisition.
Formaggio, Emanuela; Storti, Silvia Francesca; Cerini, Roberto; Fiaschi, Antonio; Manganotti, Paolo
The purpose of the present work was to investigate the correlation between topographical changes in brain oscillatory activity and the blood oxygenation level-dependent (BOLD) signal during a motor imagery (MI) task using electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) coregistration. EEG was recorded in 7 healthy subjects inside a 1.5 T MR scanner during the imagination of the kinesthetic experience of movement. A Fast Fourier Transform was applied to EEG signal in the rest and active conditions. We used the event-related-synchronization (ERS)/desynchronization (ERD) approach to characterize where the imagination of movement produces a decrease in alpha and beta power. The mean alpha map showed ERD decrease localized over the contralateral sensory motor area (SM1c) and a light desynchronization in the ipsilateral sensory motor area (SM1i); whereas the mean beta map showed ERD decrease over the supplementary motor area (SMA). fMRI showed significant activation in SMA, SM1c, SM1i. The correlation is negative in the contralateral side and positive in the ipsilateral side. Using combined EEG-fMRI signals we obtained useful new information on the description of the changes in oscillatory activity in alpha and beta bands during MI and on the investigation of the sites of BOLD activity as possible sources in generating these rhythms. By correlating BOLD and ERD/ERS we may identify more accurately which regions contribute to changes of the electrical response.
Figueroa, Roger; An, Ruopeng
Objectives Preschoolers 3-5 years of age are in a crucial stage of motor skill competence. While preschoolers develop their motor skill competence through engagement in physical activity, a majority of them fail to meet guideline-recommended physical activity level. This study reviews scientific evidence on the relationship between motor skill competence and physical activity among preschoolers. Methods This systematic review followed the PRISMA framework. Keyword and reference search were conducted in PubMed, Cochrane Library, PsycINFO, Web of Science, and Google Scholar. Inclusion criteria included-age: 3-5 years of age; setting: preschool environment (e.g., preschool, childcare, head start); main outcomes: motor skill competence and physical activity; study design: cross-sectional study, case-control study, retrospective cohort study, prospective cohort study, or randomized controlled trial; language: English; and article type: peer-reviewed publication. Results Eleven studies met the inclusion criteria, including 6 randomized controlled trials and 5 cross-sectional studies. Studies were conducted in 5 countries: United States (5), United Kingdom (2), Australia (2), Switzerland (1), and Finland (1). Eight out of the 11 studies included in the review reported a significant relationship between motor skill competence and physical activity. The specific pattern and strength of the relationship tend to differ by gender, physical activity intensity, motor skill type, and day of the week (weekdays versus weekends). Conclusions An association has been consistently documented between motor skill competence and physical activity. Future research is warranted to elucidate the underlining causal link, examine potential heterogeneity, and determine the role of environment in the relationship between motor skill competence and physical activity among preschoolers.
Wessel, Jan R
Inhibitory control enables humans to stop prepotent motor activity, and is commonly studied using go/no-go or stop-signal tasks. In stop-signal tasks, prepotent motor activity is elicited by delaying stop signals relative to go signals. In go/no-go tasks, however, trials include only one signal-go or no-go. Hence, prepotent motor activity has to be ensured differently-for example, by using rare no-go trials and short trial durations. However, a literature survey shows that ∼40% of studies use equiprobable go/no-go trials and ∼20% use long stimulus-stimulus intervals (> 4 s). It is unclear whether such slow-paced, equiprobable go/no-go tasks elicit prepotent motor activity and probe inhibitory control. We recorded EEG during four go/no-go tasks, varying in no-go probability and trial duration. We quantified prepotent motor activity on successfully inhibited no-go trials using the lateralized readiness potential. Only fast-paced go/no-go tasks with rare no-go trials reliably evoked such activity. We then used a stop-signal task and independent component analysis to isolate an established neural signature of inhibitory control, and investigated this signature's activity across the go/no-go tasks. Across tasks, increased prepotent motor activity on individual no-go trials was accompanied by greater frontocentral P3 amplitudes, confirming it as an index of inhibition. Crucially, this inhibition-related activity showed a 75% reduction in slow-paced, equiprobable go/no-go tasks compared to fast-paced, rare no-go versions. Therefore, since many common go/no-go task configurations do not reliably evoke prepotent motor activity, their inhibitory requirements are greatly reduced. This has major implications for the usage of go/no-go tasks in psychological experiments.
Anishchenko, Lesya N.; Ivashov, Sergey I.; Vasiliev, Igor A.
The paper contains feasibility study of a method for bioradar monitoring of small laboratory animals loco-motor activity improved by using a corner reflector. It presents results of mathematical simulation of bioradar signal reflection from the animal with the help of finite-difference time-domain method. It was proved both by theoretical and experimental results that a corner reflector usage during monitoring of small laboratory animals loco-motor activity improved the effectiveness of the method by reducing the dependency of the power flux density level from the distance between antennas block and the object.
Tang, Xiangdong; Yang, Linghui; Sanford, Larry D
We examined individual differences in sleep and motor activity across 2 consecutive days in rats. EEG and motor activity were recorded via telemetry in Wistar rats (n=29) for 48h under well-habituated conditions. Rats were grouped based on sleep amounts and stability across days (short [SS, n=7], intermediate [IS, n=15] and long [LS, n=7] sleep) and comparisons were conducted to determine group differences for measures of sleep and motor activity. We found that correlations across recording days were significant for all selected sleep measures and motor activity counts. Rankings for 24h total sleep time and non-rapid eye movement sleep (NREM) were SS
Marino, Barbara F.; Borghi, Anna M.; Buccino, Giovanni; Riggio, Lucia
Two experiments were carried out to investigate whether and how one important characteristic of the motor system, that is its goal-directed organization in motor chains, is reflected in language processing. This possibility stems from the embodied theory of language, according to which the linguistic system re-uses the structures of the motor system. The participants were presented with nouns of common tools preceded by a pair of verbs expressing grasping or observational motor chains (i.e., grasp-to-move, grasp-to-use, look-at-to-grasp, and look-at-to-stare). They decided whether the tool mentioned in the sentence was the same as that displayed in a picture presented shortly after. A primacy of the grasp-to-use motor chain over the other motor chains in priming the participants' performance was observed in both the experiments. More interestingly, we found that the motor information evoked by the noun was modulated by the specific motor-chain expressed by the preceding verbs. Specifically, with the grasping chain aimed at using the tool, the functional motor information prevailed over the volumetric information, and vice versa with the grasping chain aimed at moving the tool (Experiment 2). Instead, the functional and volumetric information were balanced for those motor chains that comprise at least an observational act (Experiment 1). Overall our results are in keeping with the embodied theory of language and suggest that understanding sentences expressing an action directed toward a tool drives a chained activation of the motor system. PMID:28265247
Marino, Barbara F; Borghi, Anna M; Buccino, Giovanni; Riggio, Lucia
Two experiments were carried out to investigate whether and how one important characteristic of the motor system, that is its goal-directed organization in motor chains, is reflected in language processing. This possibility stems from the embodied theory of language, according to which the linguistic system re-uses the structures of the motor system. The participants were presented with nouns of common tools preceded by a pair of verbs expressing grasping or observational motor chains (i.e., grasp-to-move, grasp-to-use, look-at-to-grasp, and look-at-to-stare). They decided whether the tool mentioned in the sentence was the same as that displayed in a picture presented shortly after. A primacy of the grasp-to-use motor chain over the other motor chains in priming the participants' performance was observed in both the experiments. More interestingly, we found that the motor information evoked by the noun was modulated by the specific motor-chain expressed by the preceding verbs. Specifically, with the grasping chain aimed at using the tool, the functional motor information prevailed over the volumetric information, and vice versa with the grasping chain aimed at moving the tool (Experiment 2). Instead, the functional and volumetric information were balanced for those motor chains that comprise at least an observational act (Experiment 1). Overall our results are in keeping with the embodied theory of language and suggest that understanding sentences expressing an action directed toward a tool drives a chained activation of the motor system.
Schneider, David M; Mooney, Richard
In the auditory system, corollary discharge signals are theorized to facilitate normal hearing and the learning of acoustic behaviors, including speech and music. Despite clear evidence of corollary discharge signals in the auditory cortex and their presumed importance for hearing and auditory-guided motor learning, the circuitry and function of corollary discharge signals in the auditory cortex are not well described. In this review, we focus on recent developments in the mouse and songbird that provide insights into the circuitry that transmits corollary discharge signals to the auditory system and the function of these signals in the context of hearing and vocal learning.
Zhen, D.; Wang, T.; Gu, F.; Ball, A. D.
Electrical motor stator current signals have been widely used to monitor the condition of induction machines and their downstream mechanical equipment. The key technique used for current signal analysis is based on Fourier transform (FT) to extract weak fault sideband components from signals predominated with supply frequency component and its higher order harmonics. However, the FT based method has limitations such as spectral leakage and aliasing, leading to significant errors in estimating the sideband components. Therefore, this paper presents the use of dynamic time warping (DTW) to process the motor current signals for detecting and quantifying common faults in a downstream two-stage reciprocating compressor. DTW is a time domain based method and its algorithm is simple and easy to be embedded into real-time devices. In this study DTW is used to suppress the supply frequency component and highlight the sideband components based on the introduction of a reference signal which has the same frequency component as that of the supply power. Moreover, a sliding window is designed to process the raw signal using DTW frame by frame for effective calculation. Based on the proposed method, the stator current signals measured from the compressor induced with different common faults and under different loads are analysed for fault diagnosis. Results show that DTW based on residual signal analysis through the introduction of a reference signal allows the supply components to be suppressed well so that the fault related sideband components are highlighted for obtaining accurate fault detection and diagnosis results. In particular, the root mean square (RMS) values of the residual signal can indicate the differences between the healthy case and different faults under varying discharge pressures. It provides an effective and easy approach to the analysis of motor current signals for better fault diagnosis of the downstream mechanical equipment of motor drives in the time
Metallo, Cinzia; Trimmer, Barry A
Recent major advances in understanding the organizational principles underlying motor control have focused on a small number of animal species with stiff articulated skeletons. These model systems have the advantage of easily quantifiable mechanics, but the neural codes underlying different movements are difficult to characterize because they typically involve a large population of neurons controlling each muscle. As a result, studying how neural codes drive adaptive changes in behavior is extremely challenging. This problem is highly simplified in the tobacco hawkmoth Manduca sexta, which, in its larval stage (caterpillar), is predominantly soft-bodied. Since each M. sexta muscle is innervated by one, occasionally two, excitatory motor neurons, the electrical activity generated by each muscle can be mapped to individual motor neurons. In the present study, muscle activation patterns were converted into motor neuron frequency patterns by identifying single excitatory junction potentials within recorded electromyographic traces. This conversion was carried out with single motor neuron resolution thanks to the high signal selectivity of newly developed flexible microelectrode arrays, which were specifically designed to record from M. sexta muscles. It was discovered that the timing of motor neuron activity and gait kinematics depend on the orientation of the plane of motion during locomotion. We report that, during climbing, the motor neurons monitored in the present study shift their activity to correlate with movements in the animal's more anterior segments. This orientation-dependent shift in motor activity is in agreement with the expected shift in the propulsive forces required for climbing. Our results suggest that, contrary to what has been previously hypothesized, M.sexta uses central command timing for adaptive load compensation.
Hu, Peter; Kalb, Robert G.; Walton, K. D. (Principal Investigator)
The survival promoting and neuroprotective actions of brain-derived neurotrophic factor (BDNF) are well known but under certain circumstances this growth factor can also exacerbate excitotoxic insults to neurons. Prior exploration of the receptor through which BDNF exerts this action on motor neurons deflects attention away from p75. Here we investigated the possibility that BDNF acts through the receptor tyrosine kinase, TrkB, to confer on motor neurons sensitivity to excitotoxic challenge. We blocked BDNF activation of TrkB using a dominant negative TrkB mutant or a TrkB function blocking antibody, and found that this protected motor neurons against excitotoxic insult in cultures of mixed spinal cord neurons. Addition of a function blocking antibody to BDNF to mixed spinal cord neuron cultures is also neuroprotective indicating that endogenously produced BDNF participates in vulnerability to excitotoxicity. We next examined the intracellular signaling cascades that are engaged upon TrkB activation. Previously we found that inhibition of the phosphatidylinositide-3'-kinase (PI3'K) pathway blocks BDNF-induced excitotoxic sensitivity. Here we show that expression of a constitutively active catalytic subunit of PI3'K, p110, confers excitotoxic sensitivity (ES) upon motor neurons not incubated with BDNF. Parallel studies with purified motor neurons confirm that these events are likely to be occuring specifically within motor neurons. The abrogation of BDNF's capacity to accentuate excitotoxic insults may make it a more attractive neuroprotective agent.
Alaerts, Kaat; Van Aggelpoel, Tinne; Swinnen, Stephan P; Wenderoth, Nicole
Several studies have demonstrated that the human motor cortex is activated by the mere observation of actions performed by others. In the present study, we explored whether the perception of 'impoverished motion stimuli', such as shadow animations, is sufficient to activate motor areas. To do so, transcranial magnetic stimulation (TMS) was applied over the hand area of the primary motor cortex (M1) while subjects observed shadow animations depicting finger motions. Data showed that resonant motor responses in M1 were only found when a biological effector was recognized from the observed shadow animation. Interestingly, M1 responses were similar for observing shadow or real motions. Therefore, the loss of 'pictorial' movement features in a shadow animation appeared to have no effect on motor resonance in M1. In summary, these findings suggest that the 'recognition' of biological motion from sparse visual input is both necessary and sufficient to recruit motor areas. This supports the hypothesis that the motor system is involved in recognizing the actions performed by others.
Kim, Minkyung; Fontelonga, Tatiana; Roesener, Andrew P; Lee, Haeram; Gurung, Suman; Mendonca, Philipe R F; Mastick, Grant S
Motor neurons differentiate from a ventral column of progenitors and settle in static clusters, the motor nuclei, next to the floor plate. Within these cell clusters, motor neurons receive afferent input and project their axons out to muscle targets. The molecular mechanisms that position motor neurons in the neural tube remain poorly understood. The floor plate produces several types of guidance cues with well-known roles in attracting and repelling axons, including the Slit family of chemorepellents via their Robo receptors, and Netrin1 via its DCC attractive receptor. In the present study we found that Islet1(+) motor neuron cell bodies invaded the floor plate of Robo1/2 double mutant mouse embryos or Slit1/2/3 triple mutants. Misplaced neurons were born in their normal progenitor column, but then migrated tangentially into the ventral midline. Robo1 and 2 receptor expression in motor neurons was confirmed by reporter gene staining and anti-Robo antibody labeling. Mis-positioned motor neurons projected their axons longitudinally within the floor plate, and failed to reach their normal exit points. To test for potential counteracting ventral attractive signals, we examined Netrin-1 and DCC mutants, and found that motor neurons shifted dorsally in the hindbrain and spinal cord, suggesting that Netrin-1/DCC signaling normally attracts motor neurons closer to the floor plate. Our results show that motor neurons are actively migrating cells, and are normally trapped in a static position by Slit/Robo repulsion and Netrin-1/DCC attraction.
Peters, Andrew J; Chen, Simon X; Komiyama, Takaki
The motor cortex is capable of reliably driving complex movements yet exhibits considerable plasticity during motor learning. These observations suggest that the fundamental relationship between motor cortex activity and movement may not be fixed but is instead shaped by learning; however, to what extent and how motor learning shapes this relationship are not fully understood. Here we addressed this issue by using in vivo two-photon calcium imaging to monitor the activity of the same population of hundreds of layer 2/3 neurons while mice learned a forelimb lever-press task over two weeks. Excitatory and inhibitory neurons were identified by transgenic labelling. Inhibitory neuron activity was relatively stable and balanced local excitatory neuron activity on a movement-by-movement basis, whereas excitatory neuron activity showed higher dynamism during the initial phase of learning. The dynamics of excitatory neurons during the initial phase involved the expansion of the movement-related population which explored various activity patterns even during similar movements. This was followed by a refinement into a smaller population exhibiting reproducible spatiotemporal sequences of activity. This pattern of activity associated with the learned movement was unique to expert animals and not observed during similar movements made during the naive phase, and the relationship between neuronal activity and individual movements became more consistent with learning. These changes in population activity coincided with a transient increase in dendritic spine turnover in these neurons. Our results indicate that a novel and reproducible activity-movement relationship develops as a result of motor learning, and we speculate that synaptic plasticity within the motor cortex underlies the emergence of reproducible spatiotemporal activity patterns for learned movements. These results underscore the profound influence of learning on the way that the cortex produces movements.
Delgado-Arredondo, Paulo Antonio; Morinigo-Sotelo, Daniel; Osornio-Rios, Roque Alfredo; Avina-Cervantes, Juan Gabriel; Rostro-Gonzalez, Horacio; Romero-Troncoso, Rene de Jesus
Nowadays, timely maintenance of electric motors is vital to keep up the complex processes of industrial production. There are currently a variety of methodologies for fault diagnosis. Usually, the diagnosis is performed by analyzing current signals at a steady-state motor operation or during a start-up transient. This method is known as motor current signature analysis, which identifies frequencies associated with faults in the frequency domain or by the time-frequency decomposition of the current signals. Fault identification may also be possible by analyzing acoustic sound and vibration signals, which is useful because sometimes this information is the only available. The contribution of this work is a methodology for detecting faults in induction motors in steady-state operation based on the analysis of acoustic sound and vibration signals. This proposed approach uses the Complete Ensemble Empirical Mode Decomposition for decomposing the signal into several intrinsic mode functions. Subsequently, the frequency marginal of the Gabor representation is calculated to obtain the spectral content of the IMF in the frequency domain. This proposal provides good fault detectability results compared to other published works in addition to the identification of more frequencies associated with the faults. The faults diagnosed in this work are two broken rotor bars, mechanical unbalance and bearing defects.
Lund, D; Ruggiero, A M; Ferguson, S M; Wright, J; English, B A; Reisz, P A; Whitaker, S M; Peltier, A C; Blakely, R D
The presynaptic, hemicholinium-3 sensitive, high-affinity choline transporter (CHT) supplies choline for acetylcholine (ACh) synthesis. In mice, a homozygous deletion of CHT (CHT-/-) leads to premature cessation of spontaneous or evoked neuromuscular signaling and is associated with perinatal cyanosis and lethality within 1 h. Heterozygous (CHT+/-) mice exhibit diminished brain ACh levels and demonstrate an inability to sustain vigorous motor activity. We sought to explore the contribution of CHT gene dosage to motor function in greater detail using transgenic mice where CHT is expressed under control of the motor neuron promoter Hb9 (Hb9:CHT). On a CHT-/- background, the Hb9:CHT transgene conferred mice with the ability to move and breath for a postnatal period of ∼24 h, thus increasing survival. Conversely, Hb9:CHT expression on a wild-type background (CHT+/+;Hb9:CHT) leads to an increased capacity for treadmill running compared to wild-type littermates. Analysis of the stimulated compound muscle action potential (CMAP) in these animals under basal conditions established that CHT+/+;Hb9:CHT mice display an unexpected, bidirectional change, producing either elevated or reduced CMAP amplitude, relative to CHT+/+ animals. To examine whether these two groups arise from underlying changes in synaptic properties, we used high-frequency stimulation of motor axons to assess CMAP recovery kinetics. Although CHT+/+; Hb9:CHT mice in the two groups display an equivalent, time-dependent reduction in CMAP amplitude, animals with a higher basal CMAP amplitude demonstrate a significantly enhanced rate of recovery. To explain our findings, we propose a model whereby CHT support for neuromuscular signaling involves contributions to ACh synthesis as well as cholinergic synaptic vesicle availability.
Felger, Jennifer C; Treadway, Michael T
Motivational and motor deficits are common in patients with depression and other psychiatric disorders, and are related to symptoms of anhedonia and motor retardation. These deficits in motivation and motor function are associated with alterations in corticostriatal neurocircuitry, which may reflect abnormalities in mesolimbic and mesostriatal dopamine (DA). One pathophysiologic pathway that may drive changes in DAergic corticostriatal circuitry is inflammation. Biomarkers of inflammation such as inflammatory cytokines and acute-phase proteins are reliably elevated in a significant proportion of psychiatric patients. A variety of inflammatory stimuli have been found to preferentially target basal ganglia function to lead to impaired motivation and motor activity. Findings have included inflammation-associated reductions in ventral striatal neural responses to reward anticipation, decreased DA and DA metabolites in cerebrospinal fluid, and decreased availability, and release of striatal DA, all of which correlated with symptoms of reduced motivation and/or motor retardation. Importantly, inflammation-associated symptoms are often difficult to treat, and evidence suggests that inflammation may decrease DA synthesis and availability, thus circumventing the efficacy of standard pharmacotherapies. This review will highlight the impact of administration of inflammatory stimuli on the brain in relation to motivation and motor function. Recent data demonstrating similar relationships between increased inflammation and altered DAergic corticostriatal circuitry and behavior in patients with major depressive disorder will also be presented. Finally, we will discuss the mechanisms by which inflammation affects DA neurotransmission and relevance to novel therapeutic strategies to treat reduced motivation and motor symptoms in patients with high inflammation.
Cantillo-Negrete, Jessica; Gutiérrez-Martínez, Josefina; Flores-Rodríguez, Teodoro B; Cariño-Escobar, Rubén I; Elías-Viñas, David
Brain computer interface systems (BCI) translate the intentions of patients affected with locked-in syndrome through the EEG signal characteristics, which are converted into commands used to control external devices. One of the strategies used, is to decode the motor imagery of the subject, which can modify the neuronal activity in the sensory-motor areas in a similar way to which it is observed in real movement. The present study shows the activation patterns that are registered in motor and motor imagery tasks of right and left hand movement in a sample of young healthy subjects of Mexican nationality. By means of frequency analysis it was possible to determine the difference conditions of motor imagery and movement. Using U Mann- Whitney tests, differences with statistical significance (p < 0.05) where obtained, in the EEG channels C3, Cz, C4, T3 and P3 in the mu and beta rhythms, for subjects with similar characteristics (age, gender, and education). With these results, it would be possible to define a classifier or decoder by gender that improves the performance rate and diminishes the training time, with the goal of designing a functional BCI system that can be transferred from the laboratory to the clinical application in patients with motor disabilities.
Gouridis, Giorgos; Karamanou, Spyridoula; Gelis, Ioannis; Kalodimos, Charalampos G.; Economou, Anastassios
Extra-cytoplasmic polypeptides are usually synthesized as “preproteins” carrying aminoterminal, cleavable signal peptides1 and secreted across membranes by translocases. The main bacterial translocase comprises the SecYEG protein-conducting channel and the peripheral ATPase motor SecA2,3. Most proteins destined for the periplasm and beyond are exported post-translationally by SecA2,3. Preprotein targeting to SecA is thought to involve signal peptides4 and chaperones like SecB5,6. Here we reveal that signal peptides have a novel role beyond targeting: they are essential allosteric activators of the translocase. Upon docking on their binding groove on SecA, signal peptides act in trans to drive three successive states: first, “triggering” that drives the translocase to a lower activation energy state; then “trapping” that engages non-native preprotein mature domains docked with high affinity on the secretion apparatus and, finally, “secretion” during which trapped mature domains undergo multiple turnovers of translocation in segments7. A significant contribution by mature domains renders signal peptides less critical in bacterial secretory protein targeting than currently assumed. Rather, it is their function as allosteric activators of the translocase that renders signal peptides essential for protein secretion. A role for signal peptides and targeting sequences as allosteric activators may be universal in protein translocases. PMID:19924216
Benages, A; Moreno-Ossett, E; Paris, F; Ridocci, M T; Blasco, E; Pastor, J; Tarazona, V; Molina, R; Mora, F
Motor activity of the colon transplant for esophageal reconstruction is a point of controversy. In this paper we present manometric studies carried out in 15 patients subjected to isoperistaltic colon interposition. Manometric studies were carried out with two polyvinyl water-filled catheters inserted through pressure transducers. Basal colonic activity and motor activity following several stimuli and "dry swallows" were registered. The type of waves after stimuli were classified as (1) synchronous, (2) sequential or progressive, and (3) segmental. Details of the basal colonic waves and colon contractions after stimuli are given: i.e., rate, duration, amplitude, interval from the stimulus, and percentage of motor activity. The data reported here indicate the good motor response of the isoperistaltic colon to intraluminal injection of water or 0. 1 N hydrochloric acid and to chachet swallowing. Only two free-symptoms patients did not have motor activity. One of them was submitted to manometric studies too soon after the operation. We conclude that the presence of sequential waves in the interposed segment likely can help to propel the contents of the colon into the stomach and to clear gastric juice if reflux from the stomach should occur.
Timofeeva, O P; Vdovichenko, N D
Development of the cardiac, respiratory, and motor activity was studied in rat fetuses with preserved placenta circulation was studied at the 16th, 18th, and 20th gestation days. The presence of three main movement types has been found: complexes of generalization activity, local movements, and jerks. In development of respiratory function, there is observed a gradual transition from individual inspirations to series of respiratory movements and then to formation of periodic respiration episodes. At the studied period, the heart rate has been found to increase. The existence of the slow-wave modulations it the heart rate with a period of 20-40 s has been revealed. Analysis of interrelations between the respiratory and motor systems has shown that in the 16-day fetuses, each respiratory movement is accompanied by extensor jerk. By the 20th days of embryonic development (E20), uncoupling of the respiratory and motor activities occurs. Comparison of the activity observed in the cardiac and somatomotor systems has shown that at E16, the cardiac rhythm fluctuations do not depend on the motor excitation jerks. In the 18-day fetuses, brief slowing down (decelerations) of the cardiac rhythm appeared during the motor activity jerks, whereas at E20, on the contrary, an increase of frequency (accelerations) of the cardiac rhythm occurred.
Okada, Jiro; Morimoto, Yusuke; Toh, Yoshihiro
The antennal motor system is activated by the muscarinic agonist pilocarpine in the American cockroach Periplaneta americana, and its output patterns were examined both in restrained intact animals and in isolated CNS preparations. The three-dimensional antennal movements induced by the hemocoelic drug injection were analyzed in in vivo preparations. Pilocarpine effectively induced prolonged rhythmic movements of both antennae. The antennae tended to describe a spatially patterned trajectory, forming loops or the symbol of infinity (infinity). Such spatial regularity is comparable to that during spontaneous tethered-walking. Rhythmic bursting activities of the antennal motor nerves in in vitro preparations were also elicited by bath application of pilocarpine. Cross-correlation analyses of the bursting spike activities revealed significant couplings among certain motor units, implying the spatial regularity of the antennal trajectory. The pilocarpine-induced rhythmic activity of antennal motor nerves was effectively suppressed by the muscarinic antagonist atropine. These results indicate that the activation of the antennal motor system is mediated by muscarinic receptors.
Haram, M.; Wang, T.; Gu, F.; Ball, A. D.
Motor current signal analysis has been an effective way for many years of monitoring electrical machines themselves. However, little work has been carried out in using this technique for monitoring their downstream equipment because of difficulties in extracting small fault components in the measured current signals. This paper investigates the characteristics of electrical current signals for monitoring the faults from a downstream gearbox using a modulation signal bispectrum (MSB), including phase effects in extracting small modulating components in a noisy measurement. An analytical study is firstly performed to understand amplitude, frequency and phase characteristics of current signals due to faults. It then explores the performance of MSB analysis in detecting weak modulating components in current signals. Experimental study based on a 10kw two stage gearbox, driven by a three phase induction motor, shows that MSB peaks at different rotational frequencies can be based to quantify the severity of gear tooth breakage and the degrees of shaft misalignment. In addition, the type and location of a fault can be recognized based on the frequency at which the change of MSB peak is the highest among different frequencies.
Chen, Chao; Shin, Duk; Watanabe, Hidenori; Nakanishi, Yasuhiko; Kambara, Hiroyuki; Yoshimura, Natsue; Nambu, Atsushi; Isa, Tadashi; Nishimura, Yukio; Koike, Yasuharu
Due to their potential as a control modality in brain-machine interfaces, electrocorticography (ECoG) has received much focus in recent years. Studies using ECoG have come out with success in such endeavors as classification of arm movements and natural grasp types, regression of arm trajectories in two and three dimensions, estimation of muscle activity time series and so on. However, there still remains considerable work to be done before a high performance ECoG-based neural prosthetic can be realized. In this study, we proposed an algorithm to decode hand trajectory from 15 and 32 channel ECoG signals recorded from primary motor cortex (M1) in two primates. To determine the most effective areas for prediction, we applied two electrode selection methods, one based on position relative to the central sulcus (CS) and another based on the electrodes' individual prediction performance. The best coefficients of determination for decoding hand trajectory in the two monkeys were 0.4815 ± 0.0167 and 0.7780 ± 0.0164. Performance results from individual ECoG electrodes showed that those with higher performance were concentrated at the lateral areas and areas close to the CS. The results of prediction according with different numbers of electrodes based on proposed methods were also shown and discussed. These results also suggest that superior decoding performance can be achieved from a group of effective ECoG signals rather than an entire ECoG array.
Clarkson, Andrew N; Overman, Justine J; Zhong, Sheng; Mueller, Rudolf; Lynch, Gary; Carmichael, S Thomas
Stroke is the leading cause of adult disability. Recovery after stroke shares similar molecular and cellular properties with learning and memory. A main component of learning-induced plasticity involves signaling through AMPA receptors (AMPARs). We systematically tested the role of AMPAR function in motor recovery in a mouse model of focal stroke. AMPAR function controls functional recovery beginning 5 d after the stroke. Positive allosteric modulators of AMPARs enhance recovery of limb control when administered after a delay from the stroke. Conversely, AMPAR antagonists impair motor recovery. The contributions of AMPARs to recovery are mediated by release of brain-derived neurotrophic factor (BDNF) in periinfarct cortex, as blocking local BDNF function in periinfarct cortex blocks AMPAR-mediated recovery and prevents the normal pattern of motor recovery. In contrast to a delayed AMPAR role in motor recovery, early administration of AMPAR agonists after stroke increases stroke damage. These findings indicate that the role of glutamate signaling through the AMPAR changes over time in stroke: early potentiation of AMPAR signaling worsens stroke damage, whereas later potentiation of the same signaling system improves functional recovery.
Llorens, Lela A.
This paper presents a review of several approaches to activity and task analysis for their selection for use in occupational therapy and proposes a neuro-behavioral approach to activity analysis and selection for use in treatment of cognitive-perceptual-motor dysfunction. (Editors/JA)
Stodden, David F.; Goodway, Jacqueline D.
Although significant attention has been given to promoting physical activity among children, little attention has been given to the developmental process of how children learn to move or to the changing role that motor skill development plays in children's physical activity levels as they grow. In order to successfully address the obesity…
Robertson, Steven S.
Cyclical fluctuation in spontaneous motor activity (CM) emerges in fetus and persists in newborn. This "resetting" experiment perturbed CM by noise stimulus during infants' active sleep. Pre- and postperturbation CM were measured and compared. Subjects were 33 infants between 1 and 3 days of age. The stimulus induced a relative slowing of CM…
Poliak, Sebastian; Morales, Daniel; Croteau, Louis-Philippe; Krawchuk, Dayana; Palmesino, Elena; Morton, Susan; Cloutier, Jean-François; Charron, Frederic; Dalva, Matthew B; Ackerman, Susan L; Kao, Tzu-Jen; Kania, Artur
During neural circuit assembly, axonal growth cones are exposed to multiple guidance signals at trajectory choice points. While axonal responses to individual guidance cues have been extensively studied, less is known about responses to combination of signals and underlying molecular mechanisms. Here, we studied the convergence of signals directing trajectory selection of spinal motor axons entering the limb. We first demonstrate that Netrin-1 attracts and repels distinct motor axon populations, according to their expression of Netrin receptors. Quantitative in vitro assays demonstrate that motor axons synergistically integrate both attractive or repulsive Netrin-1 signals together with repulsive ephrin signals. Our investigations of the mechanism of ephrin-B2 and Netrin-1 integration demonstrate that the Netrin receptor Unc5c and the ephrin receptor EphB2 can form a complex in a ligand-dependent manner and that Netrin–ephrin synergistic growth cones responses involve the potentiation of Src family kinase signaling, a common effector of both pathways. DOI: http://dx.doi.org/10.7554/eLife.10841.001 PMID:26633881
Capa, Rémi L; Marshall, Peter J; Shipley, Thomas F; Salesse, Robin N; Bouquet, Cédric A
Action perception may involve a mirror-matching system, such that observed actions are mapped onto the observer's own motor representations. The strength of such mirror system activation should depend on an individual's experience with the observed action. The motor interference effect, where an observed action interferes with a concurrently executed incongruent action, is thought to arise from mirror system activation. However, this view was recently challenged. If motor interference arises from mirror system activation, this effect should be sensitive to prior sensorimotor experience with the observed action. To test this prediction, we measured motor interference in two groups of participants observing the same incongruent movements. One group had received brief visuo-motor practice with the observed incongruent action, but not the other group. Action observation induced a larger motor interference in participants who had practiced the observed action. This result thus supports a mirror system account of motor interference.
Praamstra, P; Plat, E M; Meyer, A S; Horstink, M W
This study investigated characteristics of motor cortex activation and response generation in Parkinson's disease with measures of electrocortical activity (lateralized readiness potential [LRP]), electromyographic activity (EMG), and isometric force in a noise-compatibility task. When presented with stimuli consisting of incompatible target and distractor elements asking for responses of opposite hands, patients were less able than control subjects to suppress activation of the motor cortex controlling the wrong response hand. This was manifested in the pattern of reaction times and in an incorrect lateralization of the LRP. Onset latency and rise time of the LRP did not differ between patients and control subjects, but EMG and response force developed more slowly in patients. Moreover, in patients but not in control subjects, the rate of development of EMG and response force decreased as reaction time increased. We hypothesize that this dissociation between electrocortical activity and peripheral measures in Parkinson's disease is the result of changes in motor cortex function that alter the relation between signal-related and movement-related neural activity in the motor cortex. In the LRP, this altered balance may obscure an abnormal development of movement-related neural activity.
Serway, Christine N; Kaufman, Rebecca R; Strauss, Roland; de Belle, J Steven
The central body (or central complex, CCX) and the mushroom bodies (MBs) are brain structures in most insect phyla that have been shown to influence aspects of locomotion. The CCX regulates motor coordination and enhances activity while MBs have, thus far, been shown to suppress motor activity levels measured over time intervals ranging from hours to weeks. In this report, we investigate MB involvement in motor behavior during the initial stages (15 minutes) of walking in Buridan's paradigm. We measured aspects of walking in flies that had MB lesions induced by mutations in six different genes and by chemical ablation. All tested flies were later examined histologically to assess MB neuroanatomy. Mutant strains with MB structural defects were generally less active in walking than wild-type flies. Most mutants in which MBs were also ablated with hydroxyurea (HU) showed additional activity decrements. Variation in measures of velocity and orientation to landmarks among wild-type and mutant flies was attributed to pleiotropy, rather than to MB lesions. We conclude that MBs upregulate activity during the initial stages of walking, but suppress activity thereafter. An MB influence on decision making has been shown in a wide range of complex behaviors. We suggest that MBs provide appropriate contextual information to motor output systems in the brain, indirectly fine tuning walking by modifying the quantity (i.e., activity) of behavior.
Oishi, Kazuo; Maeshima, Takashi
Motor imagery (MI), a mental simulation of voluntary motor actions, has been used as a training method for athletes for many years. It is possible that MI techniques might similarly be useful as part of rehabilitative strategies to help people regain skills lost as a consequence of diseases or stroke. Mental activity and stress induce several different autonomic responses as part of the behavioral response to movement (e.g., motor anticipation) and as part of the central planning and preprogramming of movement. However, the interrelationships between MI, the autonomic responses, and the motor system have not yet been worked out. The authors compare a number of autonomic responses (respiration, heart rate, electro skin resistance) and motoneuron excitability (soleus H-reflex) in elite and nonelite speed skaters during MI. In contrast to the nonelite athletes, MI of elite speed skaters is characterized by larger changes in heart rate and respiration, a greater reliance on an internal perspective for MI, a more vivid MI, a more accurate correspondence between the MI and actual race times, and decreased motoneuron excitability. Two observations suggest that the changes in the autonomic responses and motoneuron excitability for the elite speed skaters are related to the effects of central motor programming: (1) there was no correlation between the autonomic responses for MI and those recorded during mental arithmetic; and (2) mental arithmetic did not significantly alter motoneuron activity. It is suggested that in elite speed skaters, the descending neural mechanisms that reduce motoneuron excitability are activated even when full, vivid MI is performed internally. These inhibitory responses of the motor system may enhance actual motor performance under conditions of remarkably high mental stress, such as that which occurs in the Olympic games.
McBride, Jennifer; Boy, Frédéric; Husain, Masud; Sumner, Petroc
Although executive control and automatic behavior have often been considered separate and distinct processes, there is strong emerging and convergent evidence that they may in fact be intricately interlinked. In this review, we draw together evidence showing that visual stimuli cause automatic and unconscious motor activation, and how this in turn has implications for executive control. We discuss object affordances, alien limb syndrome, the visual grasp reflex, subliminal priming, and subliminal triggering of attentional orienting. Consideration of these findings suggests automatic motor activation might form an intrinsic part of all behavior, rather than being categorically different from voluntary actions. PMID:22536177
Li, Mingyang; Chen, Wanzhong; Cui, Bingyi; Tian, Yantao
In this paper, in order to solve the existing problems of the low recognition rate and poor real-time performance in limb motor imagery, the integrated back-propagation neural network (IBPNN) was applied to the pattern recognition research of motor imagery EEG signals (imagining left-hand movement, imagining right-hand movement and imagining no movement). According to the motor imagery EEG data categories to be recognized, the IBPNN was designed to consist of 3 single three-layer back-propagation neural networks (BPNN), and every single neural network was dedicated to recognizing one kind of motor imagery. It simplified the complicated classification problems into three mutually independent two-class classifications by the IBPNN. The parallel computing characteristic of IBPNN not only improved the generation ability for network, but also shortened the operation time. The experimental results showed that, while comparing the single BPNN and Elman neural network, IBPNN was more competent in recognizing limb motor imagery EEG signals. Also among these three networks, IBPNN had the least number of iterations, the shortest operation time and the best consistency of actual output and expected output, and had lifted the success recognition rate above 97 percent while other single network is around 93 percent.
Lu, Siliang; Wang, Xiaoxian; He, Qingbo; Liu, Fang; Liu, Yongbin
Transient signal analysis (TSA) has been proven an effective tool for motor bearing fault diagnosis, but has yet to be applied in processing bearing fault signals with variable rotating speed. In this study, a new TSA-based angular resampling (TSAAR) method is proposed for fault diagnosis under speed fluctuation condition via sound signal analysis. By applying the TSAAR method, the frequency smearing phenomenon is eliminated and the fault characteristic frequency is exposed in the envelope spectrum for bearing fault recognition. The TSAAR method can accurately estimate the phase information of the fault-induced impulses using neither complicated time-frequency analysis techniques nor external speed sensors, and hence it provides a simple, flexible, and data-driven approach that realizes variable-speed motor bearing fault diagnosis. The effectiveness and efficiency of the proposed TSAAR method are verified through a series of simulated and experimental case studies.
Huizinga, Jan D.; Chen, Ji-Hong; Zhu, Yong Fang; Pawelka, Andrew; McGinn, Ryan J.; Bardakjian, Berj L.; Parsons, Sean P.; Kunze, Wolfgang A.; Wu, Richard You; Bercik, Premysl; Khoshdel, Amir; Chen, Sifeng; Yin, Sheng; Zhang, Qian; Yu, Yuanjie; Gao, Qingmin; Li, Kongling; Hu, Xinghai; Zarate, Natalia; Collins, Phillip; Pistilli, Marc; Ma, Junling; Zhang, Ruixue; Chen, David
The segmentation motor activity of the gut that facilitates absorption of nutrients, was first described in the late 19th century but the fundamental mechanisms underlying it remain poorly understood. The dominant theory suggests alternate excitation and inhibition from the enteric nervous system. Here we demonstrate that typical segmentation can occur after total nerve blockade. The segmentation motor pattern emerges when the amplitude of the dominant pacemaker, the slow wave generated by ICC associated with the myenteric plexus (ICC-MP), is modulated by the phase of induced lower frequency rhythmic transient depolarizations, generated by ICC associated with the deep muscular plexus (ICC-DMP), resulting in a waxing and waning of the amplitude of the slow wave and a rhythmic checkered pattern of segmentation motor activity. Phase amplitude modulation of the slow waves points to an underlying system of coupled nonlinear oscillators originating in ICC. PMID:24561718
Huizinga, Jan D; Chen, Ji-Hong; Zhu, Yong Fang; Pawelka, Andrew; McGinn, Ryan J; Bardakjian, Berj L; Parsons, Sean P; Kunze, Wolfgang A; Wu, Richard You; Bercik, Premysl; Khoshdel, Amir; Chen, Sifeng; Yin, Sheng; Zhang, Qian; Yu, Yuanjie; Gao, Qingmin; Li, Kongling; Hu, Xinghai; Zarate, Natalia; Collins, Phillip; Pistilli, Marc; Ma, Junling; Zhang, Ruixue; Chen, David
The segmentation motor activity of the gut that facilitates absorption of nutrients was first described in the late 19th century, but the fundamental mechanisms underlying it remain poorly understood. The dominant theory suggests alternate excitation and inhibition from the enteric nervous system. Here we demonstrate that typical segmentation can occur after total nerve blockade. The segmentation motor pattern emerges when the amplitude of the dominant pacemaker, the slow wave generated by interstitial cells of Cajal associated with the myenteric plexus (ICC-MP), is modulated by the phase of induced lower frequency rhythmic transient depolarizations, generated by ICC associated with the deep muscular plexus (ICC-DMP), resulting in a waxing and waning of the amplitude of the slow wave and a rhythmic checkered pattern of segmentation motor activity. Phase-amplitude modulation of the slow waves points to an underlying system of coupled nonlinear oscillators originating in the networks of ICC.
Tonetti, Lorenzo; Scher, Anat; Atun-Einy, Osnat; Samuel, Moran; Boreggiani, Michele; Natale, Vincenzo
A secondary analysis of longitudinal and cohort studies was carried out to quantitatively investigate the motor activity pattern, recorded through actigraphy, during the first six hours of nocturnal sleep. The first study was of longitudinal nature. Ten healthy participants (four females) were monitored three times, at baseline (T1) when they were infants (mean age 7.10 ± 0.32 months), at the first follow-up examination (T2) around 4 months later (mean age 11.20 ± 0.63 months) and at the second follow-up (T3) around three years later, when they were preschoolers (mean age 4.68 ± 0.14 years). At T1, T2 and T3 each participant wore the actigraph Basic Mini-Motionlogger (Ambulatory Monitoring, Inc., Ardsley, NY, USA) over at least two consecutive nycthemeral cycles, with the aim to measure the mean hourly motor activity count. Seven- and 11-month-old infants had a higher level of motor activity over the night compared to preschoolers. Furthermore, motor activity increased as the night progressed, with a pronounced increment at both T1 and T2, while at T3 such an increase was less marked. The second study was cross-sectional and aimed to explore the motor activity pattern, using actigraphy, during the first six hours of nocturnal sleep in multiple-age healthy groups, from infancy to adulthood. We assigned participants to eight groups according to age: 20 (five females) aged around 10 months old (mean age 10.65 ± 0.67 months); 13 (nine females) aged around 4 years (mean age 4.38 ± 0.51 years); 21 (10 females) aged around 10 years (mean age 9.67 ± 0.91 years); 21 (nine females) aged around 20 years (mean age 19.33 ± 2.44 years); 20 (10 females) aged around 30 years (mean age 29.80 ± 1.99 years); 20 (15 females) aged around 40 years (mean age 40.70 ± 1.26 years); 20 (11 females) aged around 50 years (mean age 50.15 ± 2.80 years) and 20 (nine females) aged around 60 years (mean age 59.25 ± 3.23 years). The participants aged between 10 and 60 years wore the
Umilta', M. Alessandra; Berchio, Cristina; Sestito, Mariateresa; Freedberg, David; Gallese, Vittorio
The role of the motor system in the perception of visual art remains to be better understood. Earlier studies on the visual perception of abstract art (from Gestalt theory, as in Arnheim, 1954 and 1988, to balance preference studies as in Locher and Stappers, 2002, and more recent work by Locher et al., 2007; Redies, 2007, and Taylor et al., 2011), neglected the question, while the field of neuroesthetics (Ramachandran and Hirstein, 1999; Zeki, 1999) mostly concentrated on figurative works. Much recent work has demonstrated the multimodality of vision, encompassing the activation of motor, somatosensory, and viscero-motor brain regions. The present study investigated whether the observation of high-resolution digitized static images of abstract paintings by Lucio Fontana is associated with specific cortical motor activation in the beholder's brain. Mu rhythm suppression was evoked by the observation of original art works but not by control stimuli (as in the case of graphically modified versions of these works). Most interestingly, previous visual exposure to the stimuli did not affect the mu rhythm suppression induced by their observation. The present results clearly show the involvement of the cortical motor system in the viewing of static abstract art works. PMID:23162456
Kokotilo, Kristen J; Eng, Janice J; Boyd, Lara A; McKeown, Martin J
Background Past studies have identified reorganization of brain activity in relation to motor outcome through standardized laboratory measures, which are quantifiable surrogates for arm use in real-life. In contrast, accelerometers can provide a real-life estimate of arm and hand usage. Methods Ten persons with chronic, subcortical stroke and ten healthy controls of similar age performed a squeeze motor task at 40% maximum voluntary contraction during fMRI. Use of the upper extremity was quantified over 3 consecutive days using wrist accelerometers. Correlations were performed between arm use and peak percent signal change (PSC) during grasp force production in six regions of interest (ROIs): bilateral primary motor cortex (M1), supplementary motor area (SMA) and premotor cortex (PM). Results Results demonstrate that in healthy controls, PSC across all ROIs did not show a relationship between arm use and brain activation during force production. In contrast, after stroke, contralesional PM and M1 showed a significant (P ≤ 0.05) correlation between increasing activation and decreasing paretic arm use, while ipsilesional PM showed a significant correlation (P ≤ 0.05) between increasing activation and decreasing non-paretic arm use. Conclusions The results of this pilot study demonstrate a negative relationship between brain activation and actual arm use after stroke. Larger studies using accelerometers that can detect amount and types of movement may offer further insight into brain reorganization and rehabilitation interventions. PMID:19737873
Pereira, Mirtes Garcia; de Oliveira, Letícia; Erthal, Fátima Smith; Joffily, Mateus; Mocaiber, Izabela F; Volchan, Eliane; Pessoa, Luiz
Affective pictures drive the activity of brain networks and impact behavior. We showed previously that viewing unpleasant pictures interfered in the performance of a basic nonemotional visual detection task. In the present study, we employed functional magnetic resonance imaging to test the hypothesis that behavioral interference may result from the interaction between negatively valenced and motor-related signals in the brain. As in our previous study (Pereira et al., 2006), participants performed a simple target detection task that followed the presentation of unpleasant or neutral pictures. Our results revealed that an unpleasant emotional context modulated evoked responses in several regions engaged by the simple target detection task. In particular, the midcingulate cortex was recruited when participants performed target detection trials during the unpleasant context, and signal responses in this region closely mirrored the pattern of behavioral interference (as revealed via reaction time). Our findings suggest that the midcingulate cortex may be an important site for the interaction between negatively valenced signals and motor signals in the brain and that it may be involved in the implementation of defensive responses, such as freezing.
Du, Yi; Buchsbaum, Bradley R.; Grady, Cheryl L.; Alain, Claude
Understanding speech in noisy environments is challenging, especially for seniors. Although evidence suggests that older adults increasingly recruit prefrontal cortices to offset reduced periphery and central auditory processing, the brain mechanisms underlying such compensation remain elusive. Here we show that relative to young adults, older adults show higher activation of frontal speech motor areas as measured by functional MRI during a syllable identification task at varying signal-to-noise ratios. This increased activity correlates with improved speech discrimination performance in older adults. Multivoxel pattern classification reveals that despite an overall phoneme dedifferentiation, older adults show greater specificity of phoneme representations in frontal articulatory regions than auditory regions. Moreover, older adults with stronger frontal activity have higher phoneme specificity in frontal and auditory regions. Thus, preserved phoneme specificity and upregulation of activity in speech motor regions provide a means of compensation in older adults for decoding impoverished speech representations in adverse listening conditions. PMID:27483187
Libertus, Klaus; Needham, Amy
Infants' preference for faces was investigated in a cross-sectional sample of 75 children, aged 3 to 11 months, and 23 adults. A visual preference paradigm was used where pairs of faces and toys were presented side-by-side while eye gaze was recorded. In addition, motor activity was assessed via parent report and the relation between motor…
The target articles in this special issue address the timely question of embodied cognition in the classroom, and in particular the potential of this approach to facilitate learning in children. The interest for motor activities within settings that typically give little space to nontraditional content is proof of a shift from a Cartesian…
Temple, Viviene A.; Crane, Jeff R.; Brown, Amy; Williams, Buffy-Lynne; Bell, Rick I.
Background: Developmental theorists suggest that physical activity during early childhood promotes fundamental motor skill (FMS) proficiency; and that differences in FMS proficiency are largely related to children's experiences. Aim: To examine associations between participation in different types of recreation/leisure and FMS proficiency of boys…
Study aim: To assess the engagement of students of Warsaw university schools in sports and in recreational motor activities. Material and methods: A cohort (n = 1100) of students attending B.S. or M.S. courses at 6 university schools in Warsaw were studied by applying questionnaire techniques. The questions pertained to participation in…
Gu, F.; Wang, T.; Alwodai, A.; Tian, X.; Shao, Y.; Ball, A. D.
Motor current signature analysis (MCSA) has been an effective way of monitoring electrical machines for many years. However, inadequate accuracy in diagnosing incipient broken rotor bars (BRB) has motivated many studies into improving this method. In this paper a modulation signal bispectrum (MSB) analysis is applied to motor currents from different broken bar cases and a new MSB based sideband estimator (MSB-SE) and sideband amplitude estimator are introduced for obtaining the amplitude at (1 ± 2 s)fs (s is the rotor slip and fs is the fundamental supply frequency) with high accuracy. As the MSB-SE has a good performance of noise suppression, the new estimator produces more accurate results in predicting the number of BRB, compared with conventional power spectrum analysis. Moreover, the paper has also developed an improved model for motor current signals under rotor fault conditions and an effective method to decouple the BRB current which interferes with that of speed oscillations associated with BRB. These provide theoretical supports for the new estimators and clarify the issues in using conventional bispectrum analysis.
Umemori, H; Ogura, H; Tozawa, N; Mikoshiba, K; Nishizumi, H; Yamamoto, T
The N-methyl-D-aspartate (NMDA) receptor, an ionotropic glutamate receptor, is implicated in motor activity that is regulated in the striatum and nucleus accumbens of the brain. A Src family kinase Lyn is highly expressed in striatum, cortex, thalamus, and cerebellum in the brain. Here we show that spontaneous motor activity is suppressed in lyn-/- mice. S.c. injection of methylphenidate, which causes accumulation of dopamine in synapses, reveals that dopaminergic pathway is normal in lyn-/- mice. After blocking the NMDA receptor, motor activity of lyn-/- mice increased to the same level as that of wild type mice. Therefore, the NMDA receptor-mediated signaling is enhanced in lyn-/- mice, indicating that Lyn regulates the NMDA receptor pathway negatively. Intriguingly, the activity of protein kinase C (PKC), an enzyme regulated downstream of NMDA receptors, is increased in lyn-/- mice. The present data suggest that the NMDA receptor signal that is enhanced in the absence of Lyn suppresses the motor activity, probably through inhibition of dopaminergic pathway at striatum. We conclude that Lyn contributes to coordination of motor activity through regulation of the NMDA pathway. It appears that this negative regulation involves suppression of downstream signaling of NMDA receptor such as those mediated by PKC.
Schmitt, Florent; Hussain, Ghulam; Dupuis, Luc; Loeffler, Jean-Philippe; Henriques, Alexandre
Motor neuron diseases (MNDs) are characterized by selective death of motor neurons and include mainly adult-onset amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). Neurodegeneration is not the single pathogenic event occurring during disease progression. There are multiple lines of evidence for the existence of defects in lipid metabolism at peripheral level. For instance, hypermetabolism is well characterized in ALS, and dyslipidemia correlates with better prognosis in patients. Lipid metabolism plays also a role in other MNDs. In SMA, misuse of lipids as energetic nutrients is described in patients and in related animal models. The composition of structural lipids in the central nervous system is modified, with repercussion on membrane fluidity and on cell signaling mediated by bioactive lipids. Here, we review the main epidemiologic and mechanistic findings that link alterations of lipid metabolism and motor neuron degeneration, and we discuss the rationale of targeting these modifications for therapeutic management of MNDs. PMID:24600344
Lin, Siming H.; Si, Jennie; Schwartz, Andrew B.
The population vector algorithm has been developed to combine the simultaneous direction- related activities of a population of motor cortical neurons to predict the trajectory of the arm movement. In our study, we consider a self-organizing model of a neural representation of the arm trajectory based on neuronal discharge rates. Self-organizing feature mapping (SOFM) is used to select the optimal set of weights in the model to determine the contribution of individual neuron to the overall movement. The correspondence between the movement directions and the discharge patterns of the motor cortical neurons is established in the output map. The topology preserving property of the SOFM is used to analyze real recorded data of a behavior monkey. The data used in this analysis were taken while the monkey was drawing spirals and doing the center out movement. Using such a statistical model, the monkey's arm moving directions could be well predicted based on the motor cortex neuronal firing information.
Sollfrank, Teresa; Hart, Daniel; Goodsell, Rachel; Foster, Jonathan; Tan, Tele
A repetitive movement practice by motor imagery (MI) can influence motor cortical excitability in the electroencephalogram (EEG). This study investigated if a realistic visualization in 3D of upper and lower limb movements can amplify motor related potentials during subsequent MI. We hypothesized that a richer sensory visualization might be more effective during instrumental conditioning, resulting in a more pronounced event related desynchronization (ERD) of the upper alpha band (10–12 Hz) over the sensorimotor cortices thereby potentially improving MI based brain-computer interface (BCI) protocols for motor rehabilitation. The results show a strong increase of the characteristic patterns of ERD of the upper alpha band components for left and right limb MI present over the sensorimotor areas in both visualization conditions. Overall, significant differences were observed as a function of visualization modality (VM; 2D vs. 3D). The largest upper alpha band power decrease was obtained during MI after a 3-dimensional visualization. In total in 12 out of 20 tasks the end-user of the 3D visualization group showed an enhanced upper alpha ERD relative to 2D VM group, with statistical significance in nine tasks.With a realistic visualization of the limb movements, we tried to increase motor cortex activation during subsequent MI. The feedback and the feedback environment should be inherently motivating and relevant for the learner and should have an appeal of novelty, real-world relevance or aesthetic value (Ryan and Deci, 2000; Merrill, 2007). Realistic visual feedback, consistent with the participant’s MI, might be helpful for accomplishing successful MI and the use of such feedback may assist in making BCI a more natural interface for MI based BCI rehabilitation. PMID:26347642
Sollfrank, Teresa; Hart, Daniel; Goodsell, Rachel; Foster, Jonathan; Tan, Tele
A repetitive movement practice by motor imagery (MI) can influence motor cortical excitability in the electroencephalogram (EEG). This study investigated if a realistic visualization in 3D of upper and lower limb movements can amplify motor related potentials during subsequent MI. We hypothesized that a richer sensory visualization might be more effective during instrumental conditioning, resulting in a more pronounced event related desynchronization (ERD) of the upper alpha band (10-12 Hz) over the sensorimotor cortices thereby potentially improving MI based brain-computer interface (BCI) protocols for motor rehabilitation. The results show a strong increase of the characteristic patterns of ERD of the upper alpha band components for left and right limb MI present over the sensorimotor areas in both visualization conditions. Overall, significant differences were observed as a function of visualization modality (VM; 2D vs. 3D). The largest upper alpha band power decrease was obtained during MI after a 3-dimensional visualization. In total in 12 out of 20 tasks the end-user of the 3D visualization group showed an enhanced upper alpha ERD relative to 2D VM group, with statistical significance in nine tasks.With a realistic visualization of the limb movements, we tried to increase motor cortex activation during subsequent MI. The feedback and the feedback environment should be inherently motivating and relevant for the learner and should have an appeal of novelty, real-world relevance or aesthetic value (Ryan and Deci, 2000; Merrill, 2007). Realistic visual feedback, consistent with the participant's MI, might be helpful for accomplishing successful MI and the use of such feedback may assist in making BCI a more natural interface for MI based BCI rehabilitation.
Stewart, Charlene Kimbro
The slide presentation depicts movement activities through which children can perceive and form concepts, thus building cognitive skills in certain areas. The presentation is based on the fact that children interact with their environments through all their senses and benefit from perceiving through their kinesthetic senses. The areas presented…
Avenanti, Alessio; Candidi, Matteo; Urgesi, Cosimo
Neurophysiological and imaging studies have shown that seeing the actions of other individuals brings about the vicarious activation of motor regions involved in performing the same actions. While this suggests a simulative mechanism mediating the perception of others' actions, one cannot use such evidence to make inferences about the functional significance of vicarious activations. Indeed, a central aim in social neuroscience is to comprehend how vicarious activations allow the understanding of other people's behavior, and this requires to use stimulation or lesion methods to establish causal links from brain activity to cognitive functions. In the present work, we review studies investigating the effects of transient manipulations of brain activity or stable lesions in the motor system on individuals' ability to perceive and understand the actions of others. We conclude there is now compelling evidence that neural activity in the motor system is critical for such cognitive ability. More research using causal methods, however, is needed in order to disclose the limits and the conditions under which vicarious activations are required to perceive and understand actions of others as well as their emotions and somatic feelings. PMID:23675338
Gawrilow, Caterina; Kühnhausen, Jan; Schmid, Johanna; Stadler, Gertraud
The aim of the present literature review is threefold. (1) We will review theories, models, and studies on symptomatic hyperactivity and motoric activity in attention-deficit/hyperactivity disorder (ADHD). (2) Another focus will be on assessment methods that have been proven to be effective in the detection of hyperactivity and motoric activity in children, adolescents, and adults with and without ADHD and emerging areas of research in the field of ADHD. We will compare subjective methods (i.e., rating scales) and objective methods (i.e., accelerometers). (3) Finally, physical activity intervention studies aiming at a modification of activity and overactive behavior will be summarized that seem to be promising candidates for alleviating hyperactivity symptoms in children, adolescents, and adults with ADHD. PMID:25506329
Luxey, Maëva; Jungas, Thomas; Laussu, Julien; Audouard, Christophe; Garces, Alain; Davy, Alice
Axon fasciculation is one of the processes controlling topographic innervation during embryonic development. While axon guidance steers extending axons in the accurate direction, axon fasciculation allows sets of co-extending axons to grow in tight bundles. The Eph:ephrin family has been involved both in axon guidance and fasciculation, yet it remains unclear how these two distinct types of responses are elicited. Herein we have characterized the role of ephrin-B1, a member of the ephrinB family in sensory and motor innervation of the limb. We show that ephrin-B1 is expressed in sensory axons and in the limb bud mesenchyme while EphB2 is expressed in motor and sensory axons. Loss of ephrin-B1 had no impact on the accurate dorso-ventral innervation of the limb by motor axons, yet EfnB1 mutants exhibited decreased fasciculation of peripheral motor and sensory nerves. Using tissue-specific excision of EfnB1 and in vitro experiments, we demonstrate that ephrin-B1 controls fasciculation of axons via a surround repulsion mechanism involving growth cone collapse of EphB2-expressing axons. Altogether, our results highlight the complex role of Eph:ephrin signaling in the development of the sensory-motor circuit innervating the limb.
Li, Zhenyu; Delaney, M. Keegan; O’Brien, Kelly A.; Du, Xiaoping
Upon vascular injury, platelets are activated by adhesion to adhesive proteins like von Willebrand factor and collagen, or by soluble platelet agonists like ADP, thrombin, and thromboxane A2. These adhesive proteins and soluble agonists induce signal transduction via their respective receptors. The various receptor-specific platelet activation signaling pathways converge into common signaling events, which stimulate platelet shape change, granule secretion, and ultimately induce the “inside-out” signaling process leading to activation of the ligand binding function of integrin αIIbβ3. Ligand binding to integrin αIIbβ3 mediates platelet adhesion and aggregation and triggers “outside-in” signaling, resulting in platelet spreading, additional granule secretion, stabilization of platelet adhesion and aggregation, and clot retraction. It has become increasingly evident that agonist-induced platelet activation signals also crosstalk with integrin “outside-in” signals to regulate platelet responses. Platelet activation involves a series of rapid positive feedback loops that greatly amplify initial activation signals, and enable robust platelet recruitment and thrombus stabilization. Recent studies have provided novel insight into the molecular mechanisms of these processes. PMID:21071698
Seybold, Heike; Boudsocq, Marie; Romeis, Tina
Calcium-dependent protein kinases undergo a rapid biochemical activation in response to an intracellular Ca increase induced by the PRR-dependent perception of a pathogen-related stimulus. Based on SDS gel resolution, the in-gel kinase assay allows the analysis of multiple in vivo protein samples in parallel, combining the advantage of protein separation according to molecular mass with the activity read-out of a protein kinase assay. It thus enables to follow the transient CDPK activation and inactivation in response to in vivo elicitation with a time-wise resolution. In addition, changes of CDPK phosphorylation activity often correlate with slight shifts in the enzyme's apparent molecular mass, indicating posttranslational modifications and a conformational change of the active enzyme compared to its inactive resting form. These band shifts can be detected by a simple immunoblotting to monitor CDPK activation.
Pinzon Morales, Ruben Dario; Hirata, Yutaka
Motor learning in the cerebellum is believed to entail plastic changes at synapses between parallel fibers and Purkinje cells, induced by the teaching signal conveyed in the climbing fiber (CF) input. Despite the abundant research on the cerebellum, the nature of this signal is still a matter of debate. Two types of movement error information have been proposed to be plausible teaching signals: sensory error (SE) and motor command error (ME); however, their plausibility has not been tested in the real world. Here, we conducted a comparison of different types of CF teaching signals in real-world engineering applications by using a realistic neuronal network model of the cerebellum. We employed a direct current motor (simple task) and a two-wheeled balancing robot (difficult task). We demonstrate that SE, ME or a linear combination of the two is sufficient to yield comparable performance in a simple task. When the task is more difficult, although SE slightly outperformed ME, these types of error information are all able to adequately control the robot. We categorize granular cells according to their inputs and the error signal revealing that different granule cells are preferably engaged for SE, ME or their combination. Thus, unlike previous theoretical and simulation studies that support either SE or ME, it is demonstrated for the first time in a real-world engineering application that both SE and ME are adequate as the CF teaching signal in a realistic computational cerebellar model, even when the control task is as difficult as stabilizing a two-wheeled balancing robot. PMID:27999381
Persson, Karin; Rekling, Jens C
Abstract The brainstem contains rhythm and pattern forming circuits, which drive cranial and spinal motor pools to produce respiratory and other motor patterns. Here we used calcium imaging combined with nerve recordings in newborn mice to reveal spontaneous population activity in the ventral brainstem and in the facial nucleus. In Fluo-8 AM loaded brainstem–spinal cord preparations, respiratory activity on cervical nerves was synchronized with calcium signals at the ventrolateral brainstem surface. Individual ventrolateral neurons at the level of the parafacial respiratory group showed perfect or partial synchrony with respiratory nerve bursts. In brainstem–spinal cord preparations, cut at the level of the mid-facial nucleus, calcium signals were recorded in the dorsal, lateral and medial facial subnuclei during respiratory activity. Strong activity initiated in the dorsal subnucleus, followed by activity in lateral and medial subnuclei. Whole-cell recordings from facial motoneurons showed weak respiratory drives, and electrical field potential recordings confirmed respiratory drive to particularly the dorsal and lateral subnuclei. Putative facial premotoneurons showed respiratory-related calcium signals, and were predominantly located dorsomedial to the facial nucleus. A novel motor activity on facial, cervical and thoracic nerves was synchronized with calcium signals at the ventromedial brainstem extending from the level of the facial nucleus to the medulla–spinal cord border. Cervical dorsal root stimulation induced similar ventromedial activity. The medial facial subnucleus showed calcium signals synchronized with this novel motor activity on cervical nerves, and cervical dorsal root stimulation induced similar medial facial subnucleus activity. In conclusion, the dorsal and lateral facial subnuclei are strongly respiratory-modulated, and the brainstem contains a novel pattern forming circuit that drives the medial facial subnucleus and cervical motor
Pérez-García, María J; Burden, Steven J
Amyotrophic lateral sclerosis (ALS) is a devastating disease that progresses from detachment of motor nerve terminals to complete muscle paralysis and lethal respiratory failure within 5 years of diagnosis. Genetic studies have linked mutations in several genes to ALS, and mice bearing mutations in SOD1 recapitulate hallmark features of the disease. We investigated whether disease symptoms can be ameliorated by co-opting the retrograde signaling pathway that promotes attachment of nerve terminals to muscle. We crossed SOD1G93A mice with transgenic mice that express MuSK, a receptor tyrosine kinase that is required for retrograde signaling, and we used histological and behavioral assays to assess motor innervation and behavior. A 3-fold increase in MuSK expression delayed the onset and reduced the extent of muscle denervation, improving motor function for more than a month without altering survival. These findings suggest that increasing MuSK activity by pharmacological means has the potential to improve motor function in ALS.
Peres, Isabella; Vetter, Céline; Blautzik, Janusch; Reiser, Maximilian; Pöppel, Ernst; Meindl, Thomas; Roenneberg, Till; Gutyrchik, Evgeny
Neuroimaging is increasingly used to study the motor system in vivo. Despite many reports of time-of-day influences on motor function at the behavioral level, little is known about these influences on neural motor networks and their activations recorded in neuroimaging. Using functional magnetic resonance imaging (fMRI), the authors studied 15 healthy subjects (9 females; mean ± SD age: 23 ± 3 yrs) performing a self-paced finger-tapping task at different times of day (morning, midday, afternoon, and evening). Blood-oxygenation-level-dependent signal showed systematic differences across the day in task-related motor areas of the brain, specifically in the supplementary motor area, parietal cortex, and rolandic operculum (p(corr)< .0125). The authors found that these time-of-day-dependent hemodynamic modulations are associated with chronotype and not with homeostatic sleep pressure. These results show that consideration of time-of-day for the analysis of fMRI studies is imperative.
Anzak, Anam; Tan, Huiling; Pogosyan, Alek; Khan, Sadaquate; Javed, Shazia; Gill, Steven S; Ashkan, Keyoumars; Akram, Harith; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Green, Alexander L; Aziz, Tipu; Brown, Peter
Enhancements in motor performance have been demonstrated in response to intense stimuli both in healthy subjects and in the form of 'paradoxical kinesis' in patients with Parkinson's disease. Here we identify a mid-latency evoked potential in local field potential recordings from the region of the subthalamic nucleus, which scales in amplitude with both the intensity of the stimulus delivered and corresponding enhancements in biomechanical measures of maximal handgrips, independent of the dopaminergic state of our subjects with Parkinson's disease. Recordings of a similar evoked potential in the related pedunculopontine nucleus - a key component of the reticular activating system - provide support for this neural signature in the subthalmic nucleus being a novel correlate of ascending arousal, propagated from the reticular activating system to exert an 'energizing' influence on motor circuitry. Future manipulation of this system linking arousal and motor performance may provide a novel approach for the non-dopaminergic enhancement of motor performance in patients with hypokinetic disorders such as Parkinson's disease.
Anzak, Anam; Tan, Huiling; Pogosyan, Alek; Khan, Sadaquate; Javed, Shazia; Gill, Steven S.; Ashkan, Keyoumars; Akram, Harith; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Green, Alexander L.; Aziz, Tipu; Brown, Peter
Enhancements in motor performance have been demonstrated in response to intense stimuli both in healthy subjects and in the form of ‘paradoxical kinesis’ in patients with Parkinson's disease. Here we identify a mid-latency evoked potential in local field potential recordings from the region of the subthalamic nucleus, which scales in amplitude with both the intensity of the stimulus delivered and corresponding enhancements in biomechanical measures of maximal handgrips, independent of the dopaminergic state of our subjects with Parkinson's disease. Recordings of a similar evoked potential in the related pedunculopontine nucleus – a key component of the reticular activating system – provide support for this neural signature in the subthalmic nucleus being a novel correlate of ascending arousal, propagated from the reticular activating system to exert an ‘energizing’ influence on motor circuitry. Future manipulation of this system linking arousal and motor performance may provide a novel approach for the non-dopaminergic enhancement of motor performance in patients with hypokinetic disorders such as Parkinson's disease. PMID:26687971
Gan, Haitao; Potter, Tom
Motor imagery electroencephalography (EEG) has been successfully used in locomotor rehabilitation programs. While the noise-assisted multivariate empirical mode decomposition (NA-MEMD) algorithm has been utilized to extract task-specific frequency bands from all channels in the same scale as the intrinsic mode functions (IMFs), identifying and extracting the specific IMFs that contain significant information remain difficult. In this paper, a novel method has been developed to identify the information-bearing components in a low-dimensional subspace without prior knowledge. Our method trains a Gaussian mixture model (GMM) of the composite data, which is comprised of the IMFs from both the original signal and noise, by employing kernel spectral regression to reduce the dimension of the composite data. The informative IMFs are then discriminated using a GMM clustering algorithm, the common spatial pattern (CSP) approach is exploited to extract the task-related features from the reconstructed signals, and a support vector machine (SVM) is applied to the extracted features to recognize the classes of EEG signals during different motor imagery tasks. The effectiveness of the proposed method has been verified by both computer simulations and motor imagery EEG datasets. PMID:27891256
Pereira, M.G.; Oliveira, L; Erthal, FS; Joffily, M; Mocaiber, I.F.; Volchan, E.; Pessoa, L.
Affective pictures drive the activity of brain networks and impact behavior. We showed previously that viewing unpleasant pictures interfered in the performance of a basic non-emotional visual detection task. In the present study, we employed functional magnetic resonance imaging to test the hypothesis that behavioral interference may result from the interaction between negatively valenced and motor-related signals in the brain. As in our previous study, subjects performed a simple target-detection task that followed the presentation of unpleasant or neutral pictures. Our results revealed that an unpleasant emotional context modulated evoked responses in several regions engaged by the simple target-detection task. In particular, the midcingulate cortex was recruited when participants performed target-detection trials during the unpleasant context and signal responses in this region closely mirrored the pattern of behavioral interference (as revealed via reaction time). Our findings suggest that the midcingulate cortex may be an important site for the interaction between negatively valenced and motor signals in the brain, and that it may be involved in the implementation of defensive responses, such as freezing. PMID:20233958
Reznik, Daniel; Ossmy, Ori; Mukamel, Roy
Accumulating evidence demonstrates that responses in auditory cortex to auditory consequences of self-generated actions are modified relative to the responses evoked by identical sounds generated by an external source. Such modifications have been suggested to occur through a corollary discharge sent from the motor system, although the exact neuroanatomical origin is unknown. Furthermore, since tactile input has also been shown to modify responses in auditory cortex, it is not even clear whether the source of such modifications is motor output or somatosensory feedback. We recorded functional magnetic resonance imaging (fMRI) data from healthy human subjects (n = 11) while manipulating the rate at which they performed sound-producing actions with their right hand. In addition, we manipulated the amount of tactile feedback to examine the relative roles of motor and somatosensory cortices in modifying evoked activity in auditory cortex (superior temporal gyrus). We found an enhanced fMRI signal in left auditory cortex during perception of self-generated sounds relative to passive listening to identical sounds. Moreover, the signal difference between active and passive conditions in left auditory cortex covaried with the rate of sound-producing actions and was invariant to the amount of tactile feedback. Together with functional connectivity analysis, our results suggest motor output from supplementary motor area and left primary motor cortex as the source of signal modification in auditory cortex during perception of self-generated sounds. Motor signals from these regions could represent a predictive signal of the expected auditory consequences of the performed action.
Ashrafi, Soha; Lalancette-Hébert, Melanie; Friese, Andreas; Sigrist, Markus; Arber, Silvia; Shneider, Neil A; Kaltschmidt, Julia A
Motor pools comprise a heterogeneous population of motor neurons that innervate distinct intramuscular targets. While the organization of motor neurons into motor pools has been well described, the time course and mechanism of motor pool diversification into functionally distinct classes remains unclear. γ-Motor neurons (γ-MNs) and α-motor neurons (α-MNs) differ in size, molecular identity, synaptic input and peripheral target. While α-MNs innervate extrafusal skeletal muscle fibers to mediate muscle contraction, γ-MNs innervate intrafusal fibers of the muscle spindle, and regulate sensitivity of the muscle spindle in response to stretch. In this study, we find that the secreted signaling molecule Wnt7a is selectively expressed in γ-MNs in the mouse spinal cord by embryonic day 17.5 and continues to molecularly distinguish γ-from α-MNs into the third postnatal week. Our data demonstrate that Wnt7a is the earliest known γ-MN marker, supporting a model of developmental divergence between α- and γ-MNs at embryonic stages. Furthermore, using Wnt7a expression as an early marker of γ-MN identity, we demonstrate a previously unknown dependence of γ-MNs on a muscle spindle-derived, GDNF-independent signal during the first postnatal week.
Brümmer, V; Schneider, S; Strüder, H K; Askew, C D
While the effects of exercise on brain cortical activity from pre-to post-exercise have been thoroughly evaluated, few studies have investigated the change in activity during exercise. As such, it is not clear to what extent changes in exercise intensity influence brain cortical activity. Furthermore, due to the difficulty in using brain-imaging methods during complex whole-body movements like cycling, it is unclear to what extent the activity in specific brain areas is altered with incremental exercise intensity over time. Latterly, active electroencephalography (EEG) electrodes combined with source localization methods allow for the assessment of brain activity, measured as EEG current density, within specific cortical regions. The present study aimed to investigate the application of this method during exercise on a cycle ergometer, and to investigate the effect of increasing exercise intensity on the magnitude and location of any changes in electrocortical current density. Subjects performed an incremental cycle ergometer test until subjective exhaustion. Current density of the EEG recordings during each test stage, as well as before and after exercise, was determined. Spatial changes in current density were localized using low-resolution brain electromagnetic tomography (LORETA) to three regions of interest; the primary motor cortex, primary sensory cortex and prefrontal cortex, and were expressed relative to current density within the local lobe. It was demonstrated that the relative current density of the primary motor cortex was intensified with increasing exercise intensity, whereas activity of the primary sensory cortex and that of the prefrontal cortex were not altered with exercise. The results indicate that the combined active EEG/LORETA method allows for the recording of brain cortical activity during complex movements and incremental exercise. These findings indicate that primary motor cortex activity is elevated with incremental exercise intensity
Molecular motors of kinesin and dynein families are responsible for various intracellular activities, from long distance movement of organelles, vesicles, protein complexes, and mRNAs to powering mitotic processes. They can take nanometer steps using chemical energy from the hydrolysis of ATP (adenosine triphosphate), and their dysfunction is involved in many neurodegenerative diseases that require long distance transport of cargos. Here I report on the study of the properties of molecular motors at a single-molecule level using optical trappings. I first studied the inhibition properties of kinesin motors by marine natural compound adociasulfates. I showed that adociasulfates compete with microtubules for binding to kinesins and thus inhibit kinesins' activity. Although adociasulfates are a strong inhibitor for all kinesin members, they show a much higher inhibition effect for conventional kinesins than for mitotic kinesins. Thus adociasulfates can be used to specifically inhibit conventional kinesins. By comparing the inhibition of kinesins by two structurally similar adociasulfates, one can see that the negatively charged sulfate residue of adociasulfates can be replaced by other negative residues and thus make it possible for adociasulfate-derived compounds to be more cell permeable. Kinesins and dyneins move cargos towards opposite directions along a microtubule. Cargos with both kinesins and dyneins attached often move bidirectionally due to undergoing a tug-of-war between the oppositely moving kinesin and dynein motors. Here I studied the effect of temperature on microtubule-based kinesin and dynein motor transport. While kinesins' and dyneins' velocities are closely matched above 15 °C, below this temperature the dyneins' velocity decreases much faster than the kinesins'. The kinesins' and dyneins' forces do not measurably change with temperature. The results suggest that temperature has significant effects on bidirectional transport and can be used to
Desai, Rutvik H; Binder, Jeffrey R; Conant, Lisa L; Seidenberg, Mark S
The sensory-motor account of conceptual processing suggests that modality-specific attributes play a central role in the organization of object and action knowledge in the brain. An opposing view emphasizes the abstract, amodal, and symbolic character of concepts, which are thought to be represented outside the brain's sensory-motor systems. We conducted a functional magnetic resonance imaging study in which the participants listened to sentences describing hand/arm action events, visual events, or abstract behaviors. In comparison to visual and abstract sentences, areas associated with planning and control of hand movements, motion perception, and vision were activated when understanding sentences describing actions. Sensory-motor areas were activated to a greater extent also for sentences with actions that relied mostly on hands, as opposed to arms. Visual sentences activated a small area in the secondary visual cortex, whereas abstract sentences activated superior temporal and inferior frontal regions. The results support the view that linguistic understanding of actions partly involves imagery or simulation of actions, and relies on some of the same neural substrate used for planning, performing, and perceiving actions.
Gagnon, Louis; Yücel, Meryem A.; Dehaes, Mathieu; Cooper, Robert J.; Perdue, Katherine L.; Selb, Juliette; Huppert, Theodore J.; Hoge, Richard D.; Boas, David A.
Near-Infrared Spectroscopy (NIRS) measures the functional hemodynamic response occuring at the surface of the cortex. Large pial veins are located above the surface of the cerebral cortex. Following activation, these veins exhibit oxygenation changes but their volume likely stays constant. The back-reflection geometry of the NIRS measurement renders the signal very sensitive to these superficial pial veins. As such, the measured NIRS signal contains contributions from both the cortical region as well as the pial vasculature. In this work, the cortical contribution to the NIRS signal was investigated using (1) Monte Carlo simulations over a realistic geometry constructed from anatomical and vascular MRI and (2) multimodal NIRS-BOLD recordings during motor stimulation. A good agreement was found between the simulations and the modeling analysis of in vivo measurements. Our results suggest that the cortical contribution to the deoxyhemoglobin signal change (ΔHbR) is equal to 16–22% of the cortical contribution to the total hemoglobin signal change (ΔHbT). Similarly, the cortical contribution of the oxyhemoglobin signal change (ΔHbO) is equal to 73–79% of the cortical contribution to the ΔHbT signal. These results suggest that ΔHbT is far less sensitive to pial vein contamination and therefore, it is likely that the ΔHbT signal provides better spatial specificity and should be used instead of ΔHbO or ΔHbR to map cerebral activity with NIRS. While different stimuli will result in different pial vein contributions, our finger tapping results do reveal the importance of considering the pial contribution. PMID:22036999
Mitchell, Amanda C; Leak, Rehana K; Garbett, Krassimira; Zigmond, Michael J; Cameron, Judy L; Mirnics, Károly
It has been established that weight gain and weight loss are heavily influenced by activity level. In this study, we hypothesized that the motor cortex exhibits a distinct physical activity-associated gene expression profile, which may underlie changes in weight associated with movement. Using DNA microarrays we profiled gene expression in the motor cortex of a group of 14 female rhesus monkeys (Macaca mulatta) with a wide range of stable physical activity levels. We found that neuronal growth factor signaling and nutrient sensing transcripts in the brain were highly correlated with physical activity. A follow-up of AKT3 expression changes (a gene at the apex of neuronal survival and nutrient sensing) revealed increased protein levels of total AKT, phosphorylated AKT, and forkhead box O3 (FOXO3), one of AKT's main downstream effectors. In addition, we successfully validated three other genes via quantitative polymerase chain reaction (qPCR) (cereblon (CRBN), origin recognition complex subunit 4-like, and pyruvate dehydrogenase 4 (PDK4)). We conclude that these genes are important in the physical activity-associated pathway in the motor cortex, and may be critical for physical activity-associated changes in body weight and neuroprotection.
Jeong, Goo-Bo; Mojsilovic-Petrovic, Jelena; Boccitto, Marco; Kalb, Robert
The survival of dorsal root ganglion and sympathetic neurons is promoted whether nerve growth factor (NGF) activates TrkA receptors on the cell body or axon. Yet other aspects of neurotrophic factor actions (i.e., ability to promote axon growth, selection of neurochemical phenotype and engagement of signaling modules) differ as a function of the location of the ligand-receptor interaction. The extent to which these observations are relevant to central nervous system neurons (CNS) is unknown. This may be particularly relevant to neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), where beneficial axon-target interactions are disturbed early in the disease process. Here we characterize the growth of pure motor neurons in compartment cultures and show that brain-derived neurotrophic factor (BDNF) stimulation of the cell body or axons/dendrites promotes survival. Expression of G37R mutant superoxide dismutase (SOD) in motor neurons will lead to death and this depends on BDNF activation of TrkB on axons and/or dendrites. BDNF action depends upon endocytosis of the BDNF-TrkB complex and de novo protein synthesis. These results highlight the importance of signaling events occurring in axons/dendrites in mutant SOD toxicity. PMID:21209215
Lee, Nancy; Neitzel, Karen L; Devlin, Brenda K; MacLennan, A John
STAT3 is a latent transcription factor that is activated by plasma membrane growth factor receptor complexes. Conditional gene disruption data indicate that it contributes to the survival of cranial motor neurons after peripheral nerve lesion. In agreement, levels of activated STAT3 (Tyr705-phosphorylated STAT3) have been shown to increase in the nuclei of adult cranial motor neurons during their regeneration after the same injury. The data presented here demonstrate that STAT3 is similarly but not identically affected in sciatic motor neurons after sciatic nerve injury. In addition, we find that sensory neuron nuclei also display an analogous increase in activated STAT3, thereby supporting a role for STAT3 in the survival and regeneration of these cells. Most interesting, the present data indicate that peripheral nerve lesion leads to a very rapid activation of STAT3 in axons at the lesion site. This response increases during the first 24 hours after injury and extends back to the motor and sensory neurons such that phospho-STAT3-immunoreactive axons are first detected in the dorsal root ganglia and ventral spinal cord at the same postlesion time intervals at which the activated STAT3 is first detected in the neuronal nuclei. Together these data raise the possibility that axonal STAT3, activated at the injury site, acts as a retrograde signaling transcription factor, which promotes the survival and regeneration of both sensory and motor neurons.
Midorikawa, Ryosuke; Takei, Yosuke; Hirokawa, Nobutaka
In brain development, apoptosis is a physiological process that controls the final numbers of neurons. Here, we report that the activity-dependent prevention of apoptosis in juvenile neurons is regulated by kinesin superfamily protein 4 (KIF4), a microtubule-based molecular motor. The C-terminal domain of KIF4 is a module that suppresses the activity of poly (ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme known to maintain cell homeostasis by repairing DNA and serving as a transcriptional regulator. When neurons are stimulated by membrane depolarization, calcium signaling mediated by CaMKII induces dissociation of KIF4 from PARP-1, resulting in upregulation of PARP-1 activity, which supports neuron survival. After dissociation from PARP-1, KIF4 enters into the cytoplasm from the nucleus and moves to the distal part of neurites in a microtubule-dependent manner. We suggested that KIF4 controls the activity-dependent survival of postmitotic neurons by regulating PARP-1 activity in brain development.
Rabuffetti, M; Meriggi, P; Pagliari, C; Bartolomeo, P; Ferrarin, M
Most applications of accelerometry-based actigraphy require a single sensor, properly located onto the body, to estimate, for example, the level of activity or the energy expenditure. Some approaches adopt a multi-sensor setup to improve those analyses or to classify different types of activity. The specific case of two symmetrically placed actigraphs allowing, by some kind of differential analysis, for the assessment of asymmetric motor behaviors, has been considered in relatively few studies. This article presents a novel method for differential actigraphy, which requires the synchronized measurements of two triaxial accelerometers (programmable eZ430-Chronos, Texas Instruments, USA) placed symmetrically on both wrists. The method involved the definition of a robust epoch-related activity index and its implementation on-board the adopted programmable platform. Finally, the activity recordings from both sensors allowed us to define a novel asymmetry index AR24 h ranging from -100% (only the left arm moves) to +100% (only the right arm moves) with null value marking a perfect symmetrical behavior. The accuracy of the AR24 h index was 1.3%. Round-the-clock monitoring on 31 healthy participants (20-79 years old, 10 left handed) provided for the AR24 h reference data (range -5% to 21%) and a fairly good correlation to the clinical handedness index (r = 0.66, p < 0.001). A subset of 20 participants repeated the monitoring one week apart evidencing an excellent test-retest reliability (r = 0.70, p < 0.001). Such figures support future applications of the methodology for the study of pathologies involving motor asymmetries, such as in patients with motor hemisyndromes and, in general, for those subjects for whom a quantification of the asymmetry in daily motor performances is required to complement laboratory tests.
Rezaei Tabar, Yousef; Halici, Ugur
Objective. Signal classification is an important issue in brain computer interface (BCI) systems. Deep learning approaches have been used successfully in many recent studies to learn features and classify different types of data. However, the number of studies that employ these approaches on BCI applications is very limited. In this study we aim to use deep learning methods to improve classification performance of EEG motor imagery signals. Approach. In this study we investigate convolutional neural networks (CNN) and stacked autoencoders (SAE) to classify EEG Motor Imagery signals. A new form of input is introduced to combine time, frequency and location information extracted from EEG signal and it is used in CNN having one 1D convolutional and one max-pooling layers. We also proposed a new deep network by combining CNN and SAE. In this network, the features that are extracted in CNN are classified through the deep network SAE. Main results. The classification performance obtained by the proposed method on BCI competition IV dataset 2b in terms of kappa value is 0.547. Our approach yields 9% improvement over the winner algorithm of the competition. Significance. Our results show that deep learning methods provide better classification performance compared to other state of art approaches. These methods can be applied successfully to BCI systems where the amount of data is large due to daily recording.
Barry, Joshua; Gu, Chen
Proper localization of various ion channels is fundamental to neuronal functions, including postsynaptic potential plasticity, dendritic integration, action potential initiation and propagation, and neurotransmitter release. Microtubule-based forward transport mediated by kinesin motors plays a key role in placing ion channel proteins to correct subcellular compartments. PDZ- and coiled-coil-domain proteins function as adaptor proteins linking ionotropic glutamate and GABA receptors to various kinesin motors, respectively. Recent studies show that several voltage-gated ion channel/transporter proteins directly bind to kinesins during forward transport. Three major regulatory mechanisms underlying intracellular transport of ion channels are also revealed. These studies contribute to understanding how mechanical forces are coupled to electrical signaling and illuminating pathogenic mechanisms in neurodegenerative diseases.
Ribchester, R R; Taxt, T
The fourth deep lumbrical muscle in the hind foot of adult rats was partially denervated by crushing the sural nerve (s.n.). The denervated muscle fibres became completely reinnervated by sprouts from lateral plantar nerve (l.p.n.) motor axons. By about 20 days after the nerve crush, s.n. motor axons started to reinnervate the muscle. In control muscles, a small proportion of the muscle fibres--about 2.5% of the muscle per motor unit--was reinnervated by s.n. motor axons over the following 20 days. Hence the regenerating terminals were able to re-establish functional synapses, despite the fact that all the muscle fibres were functionally innervated by l.p.n. terminals. When nerve impulse conduction in the l.p.n. was blocked with tetrodotoxin for up to 2 weeks, starting from the time when s.n. axons returned to the muscle, s.n. motor axons retrieved a much larger proportion of the muscle fibres--about 6.5% of the muscle per motor unit. There was a concomitant decrease in the tension produced by the sprouted l.p.n. motor axons. Intracellular recordings showed that many muscle fibres became innervated exclusively by regenerated s.n. motor nerve terminals. Measurements of end-plate potentials suggested that l.p.n. sprouts and the original nerve terminals were eliminated non-selectively. These results suggest that regenerating, active motor nerve terminals have an additional competitive advantage in reinnervating innervated muscles, if the intact terminals are inactive. When the l.p.n. was cut, rather than blocked, extensive reinnervation by the s.n. occurred-about 30% of the muscle per motor unit. This suggests that the absence of an intact nerve terminal in the motor end-plate provides a stronger stimulus than inactivity for synapse formation by regenerating motor axons. PMID:6707966
Astrakas, Loukas G; Teicher, Martin; Tzika, A Aria
The purpose of this study was to devise a paradigm that stimulates attention using a frequency-based analysis of the data acquired during a motor task. Six adults (30-40 years of age) and one child (10 years) were studied. Each subject was requested to attend to "start" and "stop" commands every 20 s alternatively and had to respond with the motor task every second time. Attention was stimulated during a block-designed, motor paradigm in which a start-stop commands cycle produced activation at the fourth harmonic of the motor frequency. We disentangled the motor and attention functions using statistical analysis with subspaces spanned by vectors generated by a truncated trigonometric series of motor and attention frequency. During our auditory-motor paradigm, all subjects showed activation in areas that belong to an extensive attention network. Attention and motor functions were coactivated but with different frequencies. While the motor-task-related areas were activated with slower frequency than attention, the activation in the attention-related areas was enhanced every time the subject had to start or end the motor task. We suggest that although a simple block-designed, auditory-motor paradigm stimulates the attention network, motor preparation, and motor inhibition concurrently, a frequency-based analysis can distinguish attention from motor functions. Due to its simplicity the paradigm can be valuable in studying children with attention deficit disorders.
Soares, Fabiano Araujo; Carvalho, João Luiz Azevedo; Miosso, Cristiano Jacques; de Andrade, Marcelino Monteiro; da Rocha, Adson Ferreira
In surface electromyography (surface EMG, or S-EMG), conduction velocity (CV) refers to the velocity at which the motor unit action potentials (MUAPs) propagate along the muscle fibers, during contractions. The CV is related to the type and diameter of the muscle fibers, ion concentration, pH, and firing rate of the motor units (MUs). The CV can be used in the evaluation of contractile properties of MUs, and of muscle fatigue. The most popular methods for CV estimation are those based on maximum likelihood estimation (MLE). This work proposes an algorithm for estimating CV from S-EMG signals, using digital image processing techniques. The proposed approach is demonstrated and evaluated, using both simulated and experimentally-acquired multichannel S-EMG signals. We show that the proposed algorithm is as precise and accurate as the MLE method in typical conditions of noise and CV. The proposed method is not susceptible to errors associated with MUAP propagation direction or inadequate initialization parameters, which are common with the MLE algorithm. Image processing -based approaches may be useful in S-EMG analysis to extract different physiological parameters from multichannel S-EMG signals. Other new methods based on image processing could also be developed to help solving other tasks in EMG analysis, such as estimation of the CV for individual MUs, localization and tracking of innervation zones, and study of MU recruitment strategies.
Alexa, Anita; Varga, János; Reményi, Attila
Signaling cascades, in addition to proteins with obvious signaling-relevant activities (e.g. protein kinases or receptors), also employ dedicated 'inactive' proteins whose functions appear to be the organization of the former components into higher order complexes through protein-protein interactions. The core function of signaling adaptors, anchors and scaffolds is the recruitment of proteins into one macromolecular complex. Several recent studies have demonstrated that the recruiter and the recruited molecules mutually influence each other in a scaffolded complex. This yields fundamentally novel properties for the signaling complex as a whole. Because these are not merely additive to the properties of the individual components, scaffolded signaling complexes may behave as functionally distinct modules.
Sergutina, A V; Rakhmanova, V I
Acetylcholinesterase activity was quantitatively evaluated by cytochemical method in brain structures (layers III and V of the sensorimotor cortex, caudate nucleus, nucleus accumbens, hippocampus CA3 field) of August and Wistar rats demonstrating high and low motor activity in the open field test. In August rats, acetylcholinesterase activity in the analyzed brain structures prevailed in animals with high motor activity in comparison with rats with low motor activity. In Wistar rats, the differences between the animals demonstrating high and low motor activity were less pronounced, but varied depending on the experimental series of studies. Comparisons of August rats with low motor activity and Wistar rats with high motor activity (maximum difference of motor function in these animals) revealed significant excess of acetylcholinesterase activity in layer III of the sensorimotor cortex in August rats and no differences in other brain structures of the examined animals.
Abdalmalak, Androu; Milej, Daniel; Diop, Mamadou; Naci, Lorina; Owen, Adrian M.; St. Lawrence, Keith
Functional near-infrared spectroscopy (fNIRS) is a non-invasive optical technique for detecting brain activity, which has been previously used during motor and motor executive tasks. There is an increasing interest in using fNIRS as a brain computer interface (BCI) for patients who lack the physical, but not the mental, ability to respond to commands. The goal of this study is to assess the feasibility of time-resolved fNIRS to detect brain activity during motor imagery. Stability tests were conducted to ensure the temporal stability of the signal, and motor imagery data were acquired on healthy subjects. The NIRS probes were placed on the scalp over the premotor cortex (PMC) and supplementary motor area (SMA), as these areas are responsible for motion planning. To confirm the fNIRS results, subjects underwent functional magnetic resonance imaging (fMRI) while performing the same task. Seven subjects have participated to date, and significant activation in the SMA and/or the PMC during motor imagery was detected by both fMRI and fNIRS in 4 of the 7 subjects. No activation was detected by either technique in the remaining three participants, which was not unexpected due to the nature of the task. The agreement between the two imaging modalities highlights the potential of fNIRS as a BCI, which could be adapted for bedside studies of patients with disorders of consciousness.
Helmbrecht, Michaela S; Soellner, Heidi; Truckenbrodt, Anna M L; Sundermeier, Julia; Cohrs, Christian; Hans, Wolfgang; de Angelis, Martin Hrabě; Feuchtinger, Annette; Aichler, Michaela; Fouad, Karim; Huber, Andrea B
The correct wiring of neuronal circuits is of crucial importance for the function of the vertebrate nervous system. Guidance cues like the neuropilin receptors (Npn) and their ligands, the semaphorins (Sema) provide a tight spatiotemporal control of sensory and motor axon growth and guidance. Among this family of guidance partners the Sema3A-Npn1 interaction has been shown to be of great importance, since defective signaling leads to wiring deficits and defasciculation. For the embryonic stage these defects have been well described, however, also after birth the organism can adapt to new challenges by compensational mechanisms. Therefore, we used the mouse lines Olig2-Cre;Npn1(cond) and Npn1(Sema-) to investigate how postnatal organisms cope with the loss of Npn1 selectively from motor neurons or a systemic dysfunctional Sema3A-Npn1 signaling in the entire organism, respectively. While in Olig2-Cre(+);Npn1(cond-/-) mice clear anatomical deficits in paw posturing, bone structure, as well as muscle and nerve composition became evident, Npn1(Sema-) mutants appeared anatomically normal. Furthermore, Olig2-Cre(+);Npn1(cond) mutants revealed a dysfunctional extensor muscle innervation after single-train stimulation of the N.radial. Interestingly, these mice did not show obvious deficits in voluntary locomotion, however, skilled motor function was affected. In contrast, Npn1(Sema-) mutants were less affected in all behavioral tests and able to improve their performance over time. Our data suggest that loss of Sema3A-Npn1 signaling is not the only cause for the observed deficits in Olig2-Cre(+);Npn1(cond-/-) mice and that additional, yet unknown binding partners for Npn1 may be involved that allow Npn1(Sema-) mutants to compensate for their developmental deficits.
Touya, Clément; Schwalger, Tilo; Lindner, Benjamin
Active Brownian particles (ABPs), obeying a nonlinear Langevin equation with speed-dependent drift and noise amplitude, are well-known models used to describe self-propelled motion in biology. In this paper we study a model describing the stochastic dynamics of a group of coupled molecular motors (CMMs). Using two independent numerical methods, one based on the stationary velocity distribution of the motors and the other one on the local increments (also known as the Kramers-Moyal coefficients) of the velocity, we establish a connection between the CMM and the ABP models. The parameters extracted for the ABP via the two methods show good agreement for both symmetric and asymmetric cases and are independent of N, the number of motors, provided that N is not too small. This indicates that one can indeed describe the CMM problem with a simpler ABP model. However, the power spectrum of velocity fluctuations in the CMM model reveals a peak at a finite frequency, a peak which is absent in the velocity spectrum of the ABP model. This implies richer dynamic features of the CMM model which cannot be captured by an ABP model.
Ultrasonic piezoelectric motor technology is an important system component in integrated mechatronics devices working on extreme operating conditions. Due to these constraints, robustness and performance of the control interfaces should be taken into account in the motor design. In this paper, we apply a new architecture for a fault tolerant control using Youla parameterization for an ultrasonic piezoelectric motor. The distinguished feature of proposed controller architecture is that it shows structurally how the controller design for performance and robustness may be done separately which has the potential to overcome the conflict between performance and robustness in the traditional feedback framework. A fault tolerant control architecture includes two parts: one part for performance and the other part for robustness. The controller design works in such a way that the feedback control system will be solely controlled by the proportional plus double-integral
Fernandino, Leonardo; Humphries, Colin J.; Seidenberg, Mark S.; Gross, William L.; Conant, Lisa L.; Binder, Jeffrey R.
While major advances have been made in uncovering the neural processes underlying perceptual representations, our grasp of how the brain gives rise to conceptual knowledge remains relatively poor. Recent work has provided strong evidence that concepts rely, at least in part, on the same sensory and motor neural systems through which they were acquired, but it is still unclear whether the neural code for concept representation uses information about sensory-motor features to discriminate between concepts. In the present study, we investigate this question by asking whether an encoding model based on five semantic attributes directly related to sensory-motor experience – sound, color, visual motion, shape, and manipulation – can successfully predict patterns of brain activation elicited by individual lexical concepts. We collected ratings on the relevance of these five attributes to the meaning of 820 words, and used these ratings as predictors in a multiple regression model of the fMRI signal associated with the words in a separate group of participants. The five resulting activation maps were then combined by linear summation to predict the distributed activation pattern elicited by a novel set of 80 test words. The encoding model predicted the activation patterns elicited by the test words significantly better than chance. As expected, prediction was successful for concrete but not for abstract concepts. Comparisons between encoding models based on different combinations of attributes indicate that all five attributes contribute to the representation of concrete concepts. Consistent with embodied theories of semantics, these results show, for the first time, that the distributed activation pattern associated with a concept combines information about different sensory-motor attributes according to their respective relevance. Future research should investigate how additional features of phenomenal experience contribute to the neural representation of conceptual
Daun-Gruhn, Silvia; Tóth, Tibor I; Borgmann, Anke
Recent experiments, reported in the accompanying paper, have supplied key data on the impact afferent excitation has on the activity of the levator–depressor motor system of an extremity in the stick insect. The main finding was that, stimulation of the campaniform sensillae of the partially amputated middle leg in an animal where all other but one front leg had been removed, had a dominating effect over that of the stepping ipsilateral front leg. In fact,the latter effect was minute compared to the former. In this article, we propose a local network that involves the neuronal part of the levator–depressor motor system and use it to elucidate the mechanisms that underlie the generation of neuronal activity in the experiments. In particular, we show that by appropriately modulating the activity in the neurons of the central pattern generator of the levator–depressor motor system, we obtain activity patterns of the motoneurons in the model that closely resemble those found in extracellular recordings in the stick insect. In addition, our model predicts specific properties of these records which depend on the stimuli applied to the stick insect leg. We also discuss our results on the segmental mechanisms in the context of inter-segmental coordination.
Newby, Jay; Bressloff, Paul C.
The tug-of-war model of motor-driven cargo transport is formulated as an intermittent trapping process. An immobile trap, representing the cellular machinery that sequesters a motor-driven cargo for eventual use, is located somewhere within a microtubule track. A particle representing a motor-driven cargo that moves randomly with a forward bias is introduced at the beginning of the track. The particle switches randomly between a fast moving phase and a slow moving phase. When in the slow moving phase, the particle can be captured by the trap. To account for the possibility that the particle avoids the trap, an absorbing boundary is placed at the end of the track. Two local signaling mechanisms—intended to improve the chances of capturing the target—are considered by allowing the trap to affect the tug-of-war parameters within a small region around itself. The first is based on a localized adenosine triphosphate (ATP) concentration gradient surrounding a synapse, and the second is based on a concentration of tau—a microtubule-associated protein involved in Alzheimer's disease—coating the microtubule near the synapse. It is shown that both mechanisms can lead to dramatic improvements in the capture probability, with a minimal increase in the mean capture time. The analysis also shows that tau can cause a cargo to undergo random oscillations, which could explain some experimental observations.
Kim, Sung-Phil; Simeral, John D.; Hochberg, Leigh R.; Donoghue, John P.; Black, Michael J.
Computer-mediated connections between human motor cortical neurons and assistive devices promise to improve or restore lost function in people with paralysis. Recently, a pilot clinical study of an intracortical neural interface system demonstrated that a tetraplegic human was able to obtain continuous two-dimensional control of a computer cursor using neural activity recorded from his motor cortex. This control, however, was not sufficiently accurate for reliable use in many common computer control tasks. Here, we studied several central design choices for such a system including the kinematic representation for cursor movement, the decoding method that translates neuronal ensemble spiking activity into a control signal and the cursor control task used during training for optimizing the parameters of the decoding method. In two tetraplegic participants, we found that controlling a cursor's velocity resulted in more accurate closed-loop control than controlling its position directly and that cursor velocity control was achieved more rapidly than position control. Control quality was further improved over conventional linear filters by using a probabilistic method, the Kalman filter, to decode human motor cortical activity. Performance assessment based on standard metrics used for the evaluation of a wide range of pointing devices demonstrated significantly improved cursor control with velocity rather than position decoding. Disclosure. JPD is the Chief Scientific Officer and a director of Cyberkinetics Neurotechnology Systems (CYKN); he holds stock and receives compensation. JDS has been a consultant for CYKN. LRH receives clinical trial support from CYKN.
Guo, Jia; Zhao, Xiaojie; Li, Yi; Yao, Li; Chen, Kewei
Real-time fMRI (rtfMRI) is a new technology which allows human subjects to observe and control their own BOLD signal change from one or more localized brain regions during scanning. Current rtfMRI-neurofeedback studies mainly focused on the target region itself without considering other related regions influenced by the real-time feedback. However, there always exits important directional influence between many of cooperative regions. On the other hand, rtfMRI based on motor imagery mainly aimed at somatomotor cortex or primary motor area, whereas supplement motor area (SMA) was a relatively more integrated and pivotal region. In this study, we investigated whether the activities of SMA can be controlled utilizing different motor imagery strategies, and whether there exists any possible impact on an unregulated but related region, primary motor cortex (M1). SMA was first localized using overt finger tapping task, the activities of SMA were feedback to subjects visually on line during each of two subsequent imagery motor movement sessions. All thirteen healthy participants were found to be able to successfully control their SMA activities by self-fit imagery strategies which involved no actual motor movements. The activation of right M1 was also found to be significantly reduced in both intensity and extent with the neurofeedback process targeted at SMA, suggestive that not only the part of motor cortex activities were influenced under the regulation of a key region SMA, but also the increased difference between SMA and M1 might reflect the potential learning effect.
Butler, Andrew J; James, Karin Harman
Our experience with the world commonly involves physical interaction with objects enabling us to learn associations between multisensory information perceived during an event and our actions that create an event. The interplay among active interactions during learning and multisensory integration of object properties is not well understood. To better understand how action might enhance multisensory associative recognition, we investigated the interplay among motor and perceptual systems after active learning. Fifteen participants were included in an fMRI study during which they learned visuo-auditory-motor associations between novel objects and the sounds they produce, either through self-generated actions on the objects (active learning) or by observing an experimenter produce the actions (passive learning). Immediately after learning, behavioral and BOLD fMRI measures were collected while perceiving the objects used during unisensory and multisensory training in associative perception and recognition tasks. Active learning was faster and led to more accurate recognition of audiovisual associations than passive learning. Functional ROI analyses showed that in motor, somatosensory, and cerebellar regions there was greater activation during both the perception and recognition of actively learned associations. Finally, functional connectivity between visual- and motor-related processing regions was enhanced during the presentation of actively learned audiovisual associations. Overall, the results of the current study clarify and extend our own previous work [Butler, A. J., James, T. W., & Harman James, K. Enhanced multisensory integration and motor reactivation after active motor learning of audiovisual associations. Journal of Cognitive Neuroscience, 23, 3515-3528, 2011] by providing several novel findings and highlighting the task-based nature of motor reactivation and retrieval after active learning.
Pariente, J; Loubinoux, I; Carel, C; Albucher, J F; Leger, A; Manelfe, C; Rascol, O; Chollet, F
In order to determine the influence of a single dose of fluoxetine on the cerebral motor activation of lacunar stroke patients in the early phase of recovery, we conducted a prospective, double-blind, crossover, placebo-controlled study on 8 patients with pure motor hemiparesia. Each patient underwent two functional magnetic resonance imaging (fMRI) examinations: one under fluoxetine and one under placebo. The first was performed 2 weeks after stroke onset and the second a week later. During the two fMRI examinations, patients performed an active controlled motor task with the affected hand and a passive one conducted by the examiner with the same hand. Motor performance was evaluated by motor tests under placebo and under fluoxetine immediately before the examinations to investigate the effect of fluoxetine on motor function. Under fluoxetine, during the active motor task, hyperactivation in the ipsilesional primary motor cortex was found. Moreover, fluoxetine significantly improved motor skills of the affected side. We found that a single dose of fluoxetine was enough to modulate cerebral sensory-motor activation in patients. This redistribution of activation toward the motor cortex output activation was associated with an enhancement of motor performance.
Erlacher, Daniel; Schredl, Michael
The present study investigated the relationship between the time required for specific tasks (counting and performing squats) in lucid dreams and in the waking state. Five proficient lucid dreamers (26-34 yr. old, M=29.8, SD=3.0; one woman and four men) participated. Analysis showed that the time needed for counting in a lucid dream is comparable to the time needed for counting in wakefulness, but motor activities required more time in lucid dreams than in the waking state.
Hou, Li J.; Song, Zheng; Pan, Zhu J.; Cheng, Jia L.; Yu, Yong; Wang, Jun
One aspect of motor fatigue is the exercise-induced reduction of neural activity to voluntarily drive the muscle or muscle group. Functional magnetic resonance imaging provides access to investigate the neural activation on the whole brain level and studies observed changes of activation intensity after exercise-induced motor fatigue in the sensorimotor cortex. However, in human, little evidence exists to demonstrate the role of subcortical brain regions in motor fatigue, which is contradict to abundant researches in rodent indicating that during simple movement, the activity of the basal ganglia is modulated by the state of motor fatigue. Thus, in present study, we explored the effect of motor fatigue on subcortical areas in human. A series of fMRI data were collected from 11 healthy subjects while they were executing simple motor tasks in two conditions: before and under the motor fatigue state. The results showed that in both conditions, movements evoked activation volumes in the sensorimotor areas, SMA, cerebellum, thalamus, and basal ganglia. Of primary importance are the results that the intensity and size of activation volumes in the subcortical areas (i.e., thalamus and basal ganglia areas) are significantly decreased during the motor fatigue state, implying that motor fatigue disturbs the motor control processing in a way that both sensorimotor areas and subcortical brain areas are less active. Further study is needed to clarify how subcortical areas contribute to the overall decreased activity of CNS during motor fatigue state. PMID:27536264
Binari, Laura A.; Lewis, Gwendolyn M.; Kucenas, Sarah
Motor nerves play the critical role of shunting information out of the CNS to targets in the periphery. Their formation requires the coordinated development of distinct cellular components, including motor axons and the Schwann cells and perineurial glia that ensheath them. During nervous system assembly, these glial cells must migrate long distances and terminally differentiate, ensuring the efficient propagation of action potentials. Although we know quite a bit about the mechanisms that control Schwann cell development during this process, nothing is known about the mechanisms that mediate the migration and differentiation of perineurial glia. Using in vivo imaging in zebrafish, we demonstrate that Notch signaling is required for both perineurial migration and differentiation during nerve formation, but not regeneration. Interestingly, loss of Notch signaling in perineurial cells also causes a failure of Schwann cell differentiation, demonstrating that Schwann cells require perineurial glia for aspects of their own development. These studies describe a novel mechanism that mediates multiple aspects of perineurial development and reveal the critical importance of perineurial glia for Schwann cell maturation and nerve formation. PMID:23467342
Wu, Hao; Siu, Wan-Chi
Moving object detection from a moving camera is a fundamental task in many applications. For the moving robot car vision, the background movement is 3D motion structure in nature. In this situation, the conventional moving object detection algorithm cannot be use to handle the 3D background modeling effectively and efficiently. In this paper, a novel scheme is proposed by utilizing the motor control signal and depth map obtained from a stereo camera to model the perspective transform matrix between different frames under a moving camera. In our approach, the coordinate relationship between frames during camera moving is modeled by a perspective transform matrix which is obtained by using current motor control signals and the pixel depth value. Hence, the relationship between a static background pixel and the moving foreground corresponding to the camera motion can be related by a perspective matrix. To enhance the robustness of classification, we allowed a tolerance range during the perspective transform matrix prediction and used multi-reference frames to classify the pixel on current frame. The proposed scheme has been found to be able to detect moving objects for our moving robot car efficiently. Different from conventional approaches, our method can model the moving background in 3D structure, without online model training. More importantly, the computational complexity and memory requirement are low making it possible to implement this scheme in real-time, which is even valuable for a robot vision system.
Marques, Hugo Gravato; Bharadwaj, Arjun; Iida, Fumiya
In mammals, the developmental path that links the primary behaviours observed during foetal stages to the full fledged behaviours observed in adults is still beyond our understanding. Often theories of motor control try to deal with the process of incremental learning in an abstract and modular way without establishing any correspondence with the mammalian developmental stages. In this paper, we propose a computational model that links three distinct behaviours which appear at three different stages of development. In order of appearance, these behaviours are: spontaneous motor activity (SMA), reflexes, and coordinated behaviours, such as locomotion. The goal of our model is to address in silico four hypotheses that are currently hard to verify in vivo: First, the hypothesis that spinal reflex circuits can be self-organized from the sensor and motor activity induced by SMA. Second, the hypothesis that supraspinal systems can modulate reflex circuits to achieve coordinated behaviour. Third, the hypothesis that, since SMA is observed in an organism throughout its entire lifetime, it provides a mechanism suitable to maintain the reflex circuits aligned with the musculoskeletal system, and thus adapt to changes in body morphology. And fourth, the hypothesis that by changing the modulation of the reflex circuits over time, one can switch between different coordinated behaviours. Our model is tested in a simulated musculoskeletal leg actuated by six muscles arranged in a number of different ways. Hopping is used as a case study of coordinated behaviour. Our results show that reflex circuits can be self-organized from SMA, and that, once these circuits are in place, they can be modulated to achieve coordinated behaviour. In addition, our results show that our model can naturally adapt to different morphological changes and perform behavioural transitions. PMID:25057775
Li, Xiaoyan; Liu, Jie; Li, Sheng; Wang, Ying-Chih
In this study, we used muscle and motor unit indices, derived from convenient surface electromyography (EMG) measurements, for examination of paretic muscle changes post stroke. For 12 stroke subjects, compound muscle action potential and voluntary surface EMG signals were recorded from paretic and contralateral first dorsal interosseous, abductor pollicis brevis, and abductor digiti minimi muscles. Muscle activation index (AI), motor unit number index (MUNIX), and motor unit size index (MUSIX) were then calculated for each muscle. There was a significant AI reduction for all the three muscles in paretic side compared with contralateral side, providing an evidence of muscle activation deficiency after stroke. The hand MUNIX (defined by summing the values from the three muscles) was significantly reduced in paretic side compared with contralateral side, whereas the hand MUSIX was not significantly different. Furthermore, diverse changes in MUNIX and MUSIX were observed from the three muscles. A major feature of the present examinations is the primary reliance on surface EMG, which offers practical benefits because it is noninvasive, induces minimal discomfort and can be performed quickly. PMID:24967982
Huang, Vincent S; Shadmehr, Reza; Diedrichsen, Jörn
When we learn a new skill (e.g., golf) without a coach, we are "active learners": we have to choose the specific components of the task on which to train (e.g., iron, driver, putter, etc.). What guides our selection of the training sequence? How do choices that people make compare with choices made by machine learning algorithms that attempt to optimize performance? We asked subjects to learn the novel dynamics of a robotic tool while moving it in four directions. They were instructed to choose their practice directions to maximize their performance in subsequent tests. We found that their choices were strongly influenced by motor errors: subjects tended to immediately repeat an action if that action had produced a large error. This strategy was correlated with better performance on test trials. However, even when participants performed perfectly on a movement, they did not avoid repeating that movement. The probability of repeating an action did not drop below chance even when no errors were observed. This behavior led to suboptimal performance. It also violated a strong prediction of current machine learning algorithms, which solve the active learning problem by choosing a training sequence that will maximally reduce the learner's uncertainty about the task. While we show that these algorithms do not provide an adequate description of human behavior, our results suggest ways to improve human motor learning by helping people choose an optimal training sequence.
Mamos, Arkadiusz; Wichan, Paweł; Chojnacki, Jan; Grzegorczyk, Krzysztof
In acute stage of virus hepatitis B patients often complain of dyspeptic discomfort. They may be a consequence of alimentary tract motor activity disorders including these of gallbladder. Routine ultrasonography in an early phase of virus hepatitis often reveals gallbladder wall thickening what may confirm the above thesis. Thus, a group of 15 patients in an acute phase of virus hepatitis B was subjected to examinations. Gallbladder motor activity was assessed by ultrasonographic method determining its total volume and ejection fraction and volume after test meal stimulus. First examination was performed in the first week since the appearance of yellowing of the walls, successive in 4 and 8 week of the disease. Obtained results were compared to the values obtained in the group of 25 healthy volunteers. It was found out that gallbladder volume was significantly decreased and ejection fraction increased in the acute phase of virus hepatitis B than in the controls. This may speak for gallbladder hyperreactivity in patients in the course of virus hepatitis B. These disorders decreased during two-month observation but even in the 8 week the investigated parameters differed from those found in the control group.
Riehle, A; Grammont, F; Diesmann, M; Grün, S
Movement preparation is considered to be based on central processes which are responsible for improving motor performance. For instance, it has been shown that motor cortical neurones change their activity selectively in relation to prior information about movement parameters. However, it is not clear how groups of neurones dynamically organize their activity to cope with computational demands. The aim of the study was to compare the firing rate of multiple simultaneously recorded neurones with the interaction between them by describing not only the frequency of occurrence of epochs of significant synchronization, but also its modulation in time and its changes in temporal precision during an instructed delay. Multiple single-neurone activity was thus recorded in monkey motor cortex during the performance of two different delayed multi-directional pointing tasks. In order to detect conspicuous spike coincidences in simultaneously recorded spike trains by tolerating temporal jitter ranging from 0 to 20 ms and to calculate their statistical significance, a modified method of the 'Unitary Events' analysis was used. Two main results were obtained. First, simultaneously recorded neurones synchronize their spiking activity in a highly dynamic way. Synchronization becomes significant only during short periods (about 100 to 200 ms). Several such periods occurred during a behavioural trial more or less regularly. Second, in many pairs of neurones, the temporal precision of synchronous activity was highest at the end of the preparatory period. As a matter of fact, at the beginning of this period, after the presentation of the preparatory signal, neurones significantly synchronize their spiking activity, but with low temporal precision. As time advances, significant synchronization becomes more precise. Data indicate that not only the discharge rate is involved in preparatory processes, but also temporal aspects of neuronal activity as expressed in the precise synchronization
Datta, A K; Stephens, J A
1. Motor unit synchronization has been studied in human first dorsal interosseous muscle. 2. Two needle electrodes were inserted into the muscle and the activity of pairs of motor units recorded. 3. Pre- and post-stimulus histograms of the firing of unit pairs showed a narrow central peak of duration 1.3-9.3 ms (88% of sample in the range 1-6 ms; mode 3.0 ms), together with a variable amount of synchronization of somewhat longer duration. 4. For the duration of the whole synchronization peak (85% sample in range 5-15 ms; mode between 6.1 and 8.0 ms (31% of sample], units fired between 8 and 485% times more often than would have been expected had the units been firing independently of one another. Amplitudes of the peak of the recorded histograms expressed as a proportion of control ranged from 1.8 to 10.9 (mean 3.9; bin width 160 microseconds). 5. The strength of synchronization between the firing of motor unit pairs was inversely related to differences in recruitment threshold. The largest amount of synchronization was observed for pairs of units in which both had recruitment thresholds less than 0.5 N or greater than 1.0 N. Less synchronization was found between pairs of units in which one had a recruitment threshold less than 0.05 N and the other a threshold greater than 1.0 N. 6. The time course of synchronization was well matched by the predictions of a theoretical model based on the hypothesis that underlying the observed synchronization is the joint arrival of EPSPs from branched last-order input fibres.
Amoruso, Lucia; Urgesi, Cosimo
Observing other people's actions facilitates the observer's motor system as compared with observing the same individuals at rest. This motor activation is thought to result from mirror-like activity in fronto-parietal areas, which enhances the excitability of the primary motor cortex via cortico-cortical pathways. Although covert motor activation in response to observed actions has been widely investigated between conspecifics, how humans cope with other species' actions has received less attention. For example, it remains unclear whether the human motor system is activated by observing other species' actions, and whether prior familiarity with the non-conspecific agent modulates this activation. Here, we combined single-pulse transcranial magnetic stimulation and motor-evoked potential recording to explore the impact of familiarity on motor activation during the observation of non-conspecific actions. Videos displaying actions performed either by a conspecific (human) or by a non-conspecific (dog) were shown to individuals who had prior familiarity or no familiarity at all with the non-conspecific agent. We found that, whereas individuals with long-lasting familiarity showed similar levels of motor activation for human and canine actions, individuals who had no familiarity showed higher motor activation for human than for canine actions. These findings suggest that the human motor system is flexible enough to resonate with other species, and that familiarity plays a key role in tuning this ability.
Apache, R R Goyakla
This study assessed the effectiveness of an activity-based intervention program and a direct instruction program for preschool children with disabilities. Two groups of preschool students (average age=4.1 yr.), classified as having developmental delays or at risk for such delays, were selected. They were provided 15 weeks of physical education through activity-based intervention and 15 weeks of physical education by direct instruction. Instruction was provided three times a week for 30-min. each session. In the fall semester the morning group received physical education through activity-based intervention, while the afternoon group received physical education through direct instruction. In the spring semester delivery of instruction was reversed for each group. The curriculum and activities provided to each group were identical with only the instructional delivery format altered. Two sets of pre- and post-tests using the Test of Gross Motor Development were administered before and after each 15-wk. instructional period. Group improvement in skills was compared between instructional methods. Significant improvement in both locomotor and object control skills through the activity-based intervention was found compared to direct instruction. Activity-based intervention was shown to be easily adapted to a naturalistic educational setting befitting that of preschool education.
Duregotti, Elisa; Negro, Samuele; Scorzeto, Michele; Zornetta, Irene; Dickinson, Bryan C.; Chang, Christopher J.; Montecucco, Cesare; Rigoni, Michela
An acute and highly reproducible motor axon terminal degeneration followed by complete regeneration is induced by some animal presynaptic neurotoxins, representing an appropriate and controlled system to dissect the molecular mechanisms underlying degeneration and regeneration of peripheral nerve terminals. We have previously shown that nerve terminals exposed to spider or snake presynaptic neurotoxins degenerate as a result of calcium overload and mitochondrial failure. Here we show that toxin-treated primary neurons release signaling molecules derived from mitochondria: hydrogen peroxide, mitochondrial DNA, and cytochrome c. These molecules activate isolated primary Schwann cells, Schwann cells cocultured with neurons and at neuromuscular junction in vivo through the MAPK pathway. We propose that this inter- and intracellular signaling is involved in triggering the regeneration of peripheral nerve terminals affected by other forms of neurodegenerative diseases. PMID:25605902
Urusov, I. D.; Galkin, V. I.; Likhoshvay, I. P.
An active magnetic suspension for the rotor of an electric motor is considered, especially in small or miniature high-speed devices such as gyros, microturbomachines, and machine-tool spindle drives where it would eliminate the need for extra bearings and contribute to size and weight reduction. A disk-type rotor made of a ferromagnetic material is located horizontally inside the bore of a vertical stator so that weight and external loads compensate the magnetic pull upward. This pull is generated by the magnetic field in the air gap and can be automatically controlled by an electronic feedback circuit which regulates the stator input voltage depending on the rotor position along the stator bore, with a displacement transducer on the rotor indicating the position. The performance of such a suspension with automatic control in a 3-phase induction motor is analyzed on the basis of the system of differential equations describing the behavior of the electromechanical system during axial oscillations of the rotor, assuming a constant rotor speed during the transient periods.
Humphrey, D; Duggan, C; Saha, D; Smith, D; Käs, J
Entangled polymer solutions and melts exhibit elastic, solid-like resistance to quick deformations and a viscous, fluid-like response to slow deformations. This viscoelastic behaviour reflects the dynamics of individual polymer chains driven by brownian motion: since individual chains can only move in a snake-like fashion through the mesh of surrounding polymer molecules, their diffusive transport, described by reptation, is so slow that the relaxation of suddenly imposed stress is delayed. Entangled polymer solutions and melts therefore elastically resist deforming motions that occur faster than the stress relaxation time. Here we show that the protein myosin II permits active control over the viscoelastic behaviour of actin filament solutions. We find that when each actin filament in a polymerized actin solution interacts with at least one myosin minifilament, the stress relaxation time of the polymer solution is significantly shortened. We attribute this effect to myosin's action as a 'molecular motor', which allows it to interact with randomly oriented actin filaments and push them through the solution, thus enhancing longitudinal filament motion. By superseding reptation with sliding motion, the molecular motors thus overcome a fundamental principle of complex fluids: that only depolymerization makes an entangled, isotropic polymer solution fluid for quick deformations.
Aggarwal, Vikram; Thakor, Nitish V.; Schieber, Marc H.
A few kinematic synergies identified by principal component analysis (PCA) account for most of the variance in the coordinated joint rotations of the fingers and wrist used for a wide variety of hand movements. To examine the possibility that motor cortex might control the hand through such synergies, we collected simultaneous kinematic and neurophysiological data from monkeys performing a reach-to-grasp task. We used PCA, jPCA and isomap to extract kinematic synergies from 18 joint angles in the fingers and wrist and analyzed the relationships of both single-unit and multiunit spike recordings, as well as local field potentials (LFPs), to these synergies. For most spike recordings, the maximal absolute cross-correlations of firing rates were somewhat stronger with an individual joint angle than with any principal component (PC), any jPC or any isomap dimension. In decoding analyses, where spikes and LFP power in the 100- to 170-Hz band each provided better decoding than other LFP-based signals, the first PC was decoded as well as the best decoded joint angle. But the remaining PCs and jPCs were predicted with lower accuracy than individual joint angles. Although PCs, jPCs or isomap dimensions might provide a more parsimonious description of kinematics, our findings indicate that the kinematic synergies identified with these techniques are not represented in motor cortex more strongly than the original joint angles. We suggest that the motor cortex might act to sculpt the synergies generated by subcortical centers, superimposing an ability to individuate finger movements and adapt the hand to grasp a wide variety of objects. PMID:24990564
Mollazadeh, Mohsen; Aggarwal, Vikram; Thakor, Nitish V; Schieber, Marc H
A few kinematic synergies identified by principal component analysis (PCA) account for most of the variance in the coordinated joint rotations of the fingers and wrist used for a wide variety of hand movements. To examine the possibility that motor cortex might control the hand through such synergies, we collected simultaneous kinematic and neurophysiological data from monkeys performing a reach-to-grasp task. We used PCA, jPCA and isomap to extract kinematic synergies from 18 joint angles in the fingers and wrist and analyzed the relationships of both single-unit and multiunit spike recordings, as well as local field potentials (LFPs), to these synergies. For most spike recordings, the maximal absolute cross-correlations of firing rates were somewhat stronger with an individual joint angle than with any principal component (PC), any jPC or any isomap dimension. In decoding analyses, where spikes and LFP power in the 100- to 170-Hz band each provided better decoding than other LFP-based signals, the first PC was decoded as well as the best decoded joint angle. But the remaining PCs and jPCs were predicted with lower accuracy than individual joint angles. Although PCs, jPCs or isomap dimensions might provide a more parsimonious description of kinematics, our findings indicate that the kinematic synergies identified with these techniques are not represented in motor cortex more strongly than the original joint angles. We suggest that the motor cortex might act to sculpt the synergies generated by subcortical centers, superimposing an ability to individuate finger movements and adapt the hand to grasp a wide variety of objects.
Torres, E. B.; Denisova, K.
The human body is in constant motion, from every breath that we take, to every visibly purposeful action that we perform. Remaining completely still on command is a major achievement as involuntary fluctuations in our motions are difficult to keep under control. Here we examine the noise-to-signal ratio of micro-movements present in time-series of head motions extracted from resting-state functional magnetic resonance imaging scans in 1048 participants. These included individuals with autism spectrum disorders (ASD) and healthy-controls in shared data from the Autism Brain Imaging Data Exchange (ABIDE) and the Attention-Deficit Hyperactivity Disorder (ADHD-200) databases. We find excess noise and randomness in the ASD cases, suggesting an uncertain motor-feedback signal. A power-law emerged describing an orderly relation between the dispersion and shape of the probability distribution functions best describing the stochastic properties under consideration with respect to intelligence quotient (IQ-scores). In ASD, deleterious patterns of noise are consistently exacerbated with the presence of secondary (comorbid) neuropsychiatric diagnoses, lower verbal and performance intelligence, and autism severity. Importantly, such patterns in ASD are present whether or not the participant takes psychotropic medication. These data unambiguously establish specific noise-to-signal levels of head micro-movements as a biologically informed core feature of ASD. PMID:27869148
Lorenz, Chad; Jones, Kelvin E.
Much is known about the electrophysiological variation in motoneuron somata across different motor units. However, comparatively less is known about electrophysiological variation in motor axons and how this could impact function or electrodiagnosis in healthy or diseased states. We performed nerve excitability testing on two groups of motor axons in Sprague–Dawley rats that are known to differ significantly in their chronic daily activity patterns and in the relative proportion of motor unit types: one group innervating the soleus (“slow motor axons”) and the other group innervating the tibialis anterior (“fast motor axons”) muscles. We found that slow motor axons have significantly larger accommodation compared to fast motor axons upon application of a 100 ms hyperpolarizing conditioning stimulus that is 40% of axon threshold (Z = 3.24, p = 0.001) or 20% of axon threshold (Z = 2.67, p = 0.008). Slow motor axons had larger accommodation to hyperpolarizing currents in the current-threshold measurement (-80% Z = 3.07, p = 0.002; -90% Z = 2.98, p = 0.003). In addition, we found that slow motor axons have a significantly smaller rheobase than fast motor axons (Z = -1.99, p = 0.047) accompanied by a lower threshold in stimulus-response curves. The results provide evidence that slow motor axons have greater activity of the hyperpolarization-activated inwardly rectifying cation conductance (IH) than fast motor axons. It is possible that this difference between fast and slow axons is caused by an adaptation to their chronic differences in daily activity patterns, and that this adaptation might have a functional effect on the motor unit. Moreover, these findings indicate that slow and fast motor axons may react differently to pathological conditions. PMID:25309406
Felice, Valeria D; Quigley, Eamonn M; Sullivan, Aideen M; O'Keeffe, Gerard W; O'Mahony, Siobhain M
Parkinson's disease is the second most common neurodegenerative disorder, affecting 1-2% of the population over 65 years of age. The primary neuropathology is the loss of midbrain dopaminergic neurons, resulting in characteristic motor deficits, upon which the clinical diagnosis is based. However, a number of significant non-motor symptoms (NMS) are also evident that appear to have a greater impact on the quality of life of these patients. In recent years, it has become increasingly apparent that neurobiological processes can be modified by the bi-directional communication that occurs along the brain-gut axis. The microbiota plays a key role in this communication throughout different routes in both physiological and pathological conditions. Thus, there has been an increasing interest in investigating how microbiota changes within the gastrointestinal tract may be implicated in health and disease including PD. Interestingly α-synuclein-aggregates, the cardinal neuropathological feature in PD, are present in both the submucosal and myenteric plexuses of the enteric nervous system, prior to their appearance in the brain, indicating a possible gut to brain route of "prion-like" spread. In this review we highlight the potential importance of gut to brain signalling in PD with particular focus on the role of the microbiota as major player in this communication.
Xiang, Jing; deGrauw, Xinyao; Korman, Abraham M.; Allen, Janelle R.; O'Brien, Hope L.; Kabbouche, Marielle A.; Powers, Scott W.; Hershey, Andrew D.
The cerebral cortex serves a primary role in the pathogenesis of migraine. This aberrant brain activation in migraine can be noninvasively detected with magnetoencephalography (MEG). The objective of this study was to investigate the differences in motor cortical activation between attacks (ictal) and pain free intervals (interictal) in children and adolescents with migraine using both low- and high-frequency neuromagnetic signals. Thirty subjects with an acute migraine and 30 subjects with a history of migraine, while pain free, were compared to age- and gender-matched controls using MEG. Motor cortical activation was elicited by a standardized, validated finger-tapping task. Low-frequency brain activation (1∼50 Hz) was analyzed with waveform measurements and high-frequency oscillations (65–150 Hz) were analyzed with wavelet-based beamforming. MEG waveforms showed that the ictal latency of low-frequency brain activation was significantly delayed as compared with controls, while the interictal latency of brain activation was similar to that of controls. The ictal amplitude of low-frequency brain activation was significantly increased as compared with controls, while the interictal amplitude of brain activation was similar to that of controls. The ictal source power of high-frequency oscillations was significantly stronger than that of the controls, while the interictal source power of high-frequency oscillations was significantly weaker than that of controls. The results suggest that aberrant low-frequency brain activation in migraine during a headache attack returned to normal interictally. However, high-frequency oscillations changed from ictal hyper-activation to interictal hypo-activation. Noninvasive assessment of cortical abnormality in migraine with MEG opens a new window for developing novel therapeutic strategies for childhood migraine by maintaining a balanced cortical excitability. PMID:24386250
Steinkellner, O.; Wabnitz, H.; Schmid, S.; Steingräber, R.; Schmidt, H.; Krüger, J.; Macdonald, R.
Robot-assisted motor rehabilitation proved to be an effective supplement to conventional hand-to-hand therapy in stroke patients. In order to analyze and understand motor learning and performance during rehabilitation it is desirable to develop a monitor to provide objective measures of the corresponding brain activity at the rehabilitation progress. We used a portable time-domain near-infrared reflectometer to monitor the hemodynamic brain response to distal upper extremity activities. Four healthy volunteers performed two different robot-assisted wrist/forearm movements, flexion-extension and pronation-supination in comparison with an unassisted squeeze ball exercise. A special headgear with four optical measurement positions to include parts of the pre- and postcentral gyrus provided a good overlap with the expected activation areas. Data analysis based on variance of time-of-flight distributions of photons through tissue was chosen to provide a suitable representation of intracerebral signals. In all subjects several of the four detection channels showed a response. In some cases indications were found of differences in localization of the activated areas for the various tasks.
Reymann, Anne-Cécile; Boujemaa-Paterski, Rajaa; Martiel, Jean-Louis; Guérin, Christophe; Cao, Wenxiang; Chin, Harvey F; De La Cruz, Enrique M; Théry, Manuel; Blanchoin, Laurent
The organization of actin filaments into higher-ordered structures governs eukaryotic cell shape and movement. Global actin network size and architecture are maintained in a dynamic steady state through regulated assembly and disassembly. Here, we used experimentally defined actin structures in vitro to investigate how the activity of myosin motors depends on network architecture. Direct visualization of filaments revealed myosin-induced actin network deformation. During this reorganization, myosins selectively contracted and disassembled antiparallel actin structures, while parallel actin bundles remained unaffected. The local distribution of nucleation sites and the resulting orientation of actin filaments appeared to regulate the scalability of the contraction process. This "orientation selection" mechanism for selective contraction and disassembly suggests how the dynamics of the cellular actin cytoskeleton can be spatially controlled by actomyosin contractility.
de Saram, Paulu S R; Ressurreição, Margarida; Davies, Angela J; Rollinson, David; Emery, Aidan M; Walker, Anthony J
Cyclic AMP (cAMP)-dependent protein kinase/protein kinase A (PKA) is the major transducer of cAMP signalling in eukaryotic cells. Here, using laser scanning confocal microscopy and 'smart' anti-phospho PKA antibodies that exclusively detect activated PKA, we provide a detailed in situ analysis of PKA signalling in intact adult Schistosoma mansoni, a causative agent of debilitating human intestinal schistosomiasis. In both adult male and female worms, activated PKA was consistently found associated with the tegument, oral and ventral suckers, oesophagus and somatic musculature. In addition, the seminal vesicle and gynaecophoric canal muscles of the male displayed activated PKA whereas in female worms activated PKA localized to the ootype wall, the ovary, and the uterus particularly around eggs during expulsion. Exposure of live worms to the PKA activator forskolin (50 µM) resulted in striking PKA activation in the central and peripheral nervous system including at nerve endings at/near the tegument surface. Such neuronal PKA activation was also observed without forskolin treatment, but only in a single batch of worms. In addition, PKA activation within the central and peripheral nervous systems visibly increased within 15 min of worm-pair separation when compared to that observed in closely coupled worm pairs. Finally, exposure of adult worms to forskolin induced hyperkinesias in a time and dose dependent manner with 100 µM forskolin significantly increasing the frequency of gross worm movements to 5.3 times that of control worms (P≤0.001). Collectively these data are consistent with PKA playing a central part in motor activity and neuronal communication, and possibly interplay between these two systems in S. mansoni. This study, the first to localize a protein kinase when exclusively in an activated state in adult S. mansoni, provides valuable insight into the intricacies of functional protein kinase signalling in the context of whole schistosome physiology.
Johnson, Luke A; Xu, Weidong; Baker, Kenneth B; Zhang, Jianyu; Vitek, Jerrold L
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established surgical therapy for advanced Parkinson's disease (PD). An emerging hypothesis is that the therapeutic benefit of DBS is derived from direct modulation of primary motor cortex (M1), yet little is known about the influence of STN DBS on individual neurons in M1. We investigated the effect of STN DBS, delivered at discrete interval intensities (20, 40, 60, 80, and 100%) of corticospinal tract threshold (CSTT), on motor performance and M1 neuronal activity in a naive nonhuman primate. Motor performance during a food reach and retrieval task improved during low-intensity stimulation (20% CSTT) but worsened as intensity approached the threshold for activation of corticospinal fibers (80% and 100% CSTT). To assess cortical effects of STN DBS, spontaneous, extracellular neuronal activity was collected from M1 neurons before, during, and after DBS at the same CSTT stimulus intensities. STN DBS significantly modulated the firing of a majority of M1 neurons; however, the direction of effect varied with stimulus intensity such that, at 20% CSTT, most neurons were suppressed, whereas at the highest stimulus intensities the majority of neurons were activated. At a population level, firing rates increased as stimulus intensity increased. These results show that STN DBS influences both motor performance and M1 neuronal activity systematically according to stimulus intensity. In addition, the unanticipated reduction in reach times suggests that STN DBS, at stimulus intensities lower than typically used for treatment of PD motor signs, can enhance normal motor performance.
Semmler, J G
It is well known that unaccustomed eccentric exercise leads to muscle damage and soreness, which can produce long-lasting effects on muscle function. How this muscle damage influences muscle activation is poorly understood. The purpose of this brief review is to highlight the effect of eccentric exercise on the activation of muscle by the nervous system, by examining the change in motor unit activity obtained from surface electromyography (EMG) and intramuscular recordings. Previous research shows that eccentric exercise produces unusual changes in the EMG–force relation that influences motor performance during isometric, shortening and lengthening muscle contractions and during fatiguing tasks. When examining the effect of eccentric exercise at the single motor unit level, there are substantial changes in recruitment thresholds, discharge rates, motor unit conduction velocities and synchronization, which can last for up to 1 week after eccentric exercise. Examining the time course of these changes suggests that the increased submaximal EMG after eccentric exercise most likely occurs through a decrease in motor unit conduction velocity and an increase in motor unit activity related to antagonist muscle coactivation and low-frequency fatigue. Furthermore, there is a commonly held view that eccentric exercise produces preferential damage to high-threshold motor units, but the evidence for this in humans is limited. Further research is needed to establish whether there is preferential damage to high-threshold motor units after eccentric exercise in humans, preferably by linking changes in motor unit activity with estimates of motor unit size using selective intramuscular recording techniques.
Chen, H. X.; Chua, Patrick S. K.; Lim, G. H.
The machinery fault diagnosis is important for improving reliability and performance of systems. Many methods such as Time Synchronous Average (TSA), Fast Fourier Transform (FFT)-based spectrum analysis and short-time Fourier transform (STFT) have been applied in fault diagnosis and condition monitoring of mechanical system. The above methods analyze the signal in frequency domain with low resolution, which is not suitable for non-stationary vibration signal. The Kolmogorov-Smirnov (KS) test is a simple and precise technique in vibration signal analysis for machinery fault diagnosis. It has limited use and advantage to analyze the vibration signal with higher noise directly. In this paper, a new method for the fault degradation assessment of the water hydraulic motor is proposed based on Wavelet Packet Analysis (WPA) and KS test to analyze the impulsive energy of the vibration signal, which is used to detect the piston condition of water hydraulic motor. WPA is used to analyze the impulsive vibration signal from the casing of the water hydraulic motor to obtain the impulsive energy. The impulsive energy of the vibration signal can be obtained by the multi-decomposition based on Wavelet Packet Transform (WPT) and used as feature values to assess the fault degradation of the pistons. The kurtosis of the impulsive energy in the reconstructed signal from the Wavelet Packet coefficients is used to extract the feature values of the impulse energy by calculating the coefficients of the WPT multi-decomposition. The KS test is used to compare the kurtosis of the impulse energy of the vibration signal statistically under the different piston conditions. The results show the applicability and effectiveness of the proposed method to assess the fault degradation of the pistons in the water hydraulic motor.
Peterson, EJ; Tyler, DJ
Objective Localized activation of peripheral axons may improve selectivity of peripheral nerve interfaces. Infrared neural stimulation (INS) employs localized delivery to activate neural tissue. This study investigated INS to determine whether localized delivery limited functionality in larger mammalian nerves. Approach The rabbit sciatic nerve was stimulated extraneurally with 1875 nm-wavelength infrared light, electrical stimulation, or a combination of both. Infrared-sensitive regions (ISR) of the nerve surface and electromyogram (EMG) recruitment of the Medial Gastrocnemius, Lateral Gastrocnemius, Soleus, and Tibialis Anterior were the primary output measures. Stimulation applied included infrared-only, electrical-only, and combined infrared and electrical. Main results 81% of nerves tested were sensitive to INS, with 1.7± 0.5 ISR detected per nerve. INS was selective to a single muscle within 81% of identified ISR. Activation energy threshold did not change significantly with stimulus power, but motor activation decreased significantly when radiant power was decreased. Maximum INS levels typically recruited up to 2–9% of any muscle. Combined infrared and electrical stimulation differed significantly from electrical recruitment in 7% of cases. Significance The observed selectivity of INS indicates it may be useful in augmenting rehabilitation, but significant challenges remain in increasing sensitivity and response magnitude to improve the functionality of INS. PMID:24310923
Peterson, E. J.; Tyler, D. J.
Objective. Localized activation of peripheral axons may improve selectivity of peripheral nerve interfaces. Infrared neural stimulation (INS) employs localized delivery to activate neural tissue. This study investigated INS to determine whether localized delivery limited functionality in larger mammalian nerves. Approach. The rabbit sciatic nerve was stimulated extraneurally with 1875 nm wavelength infrared light, electrical stimulation, or a combination of both. Infrared-sensitive regions (ISR) of the nerve surface and electromyogram (EMG) recruitment of the Medial Gastrocnemius, Lateral Gastrocnemius, Soleus, and Tibialis Anterior were the primary output measures. Stimulation applied included infrared-only, electrical-only, and combined infrared and electrical. Main results. 81% of nerves tested were sensitive to INS, with 1.7 ± 0.5 ISR detected per nerve. INS was selective to a single muscle within 81% of identified ISR. Activation energy threshold did not change significantly with stimulus power, but motor activation decreased significantly when radiant power was decreased. Maximum INS levels typically recruited up to 2-9% of any muscle. Combined infrared and electrical stimulation differed significantly from electrical recruitment in 7% of cases. Significance. The observed selectivity of INS indicates that it may be useful in augmenting rehabilitation, but significant challenges remain in increasing sensitivity and response magnitude to improve the functionality of INS.
Colombres, Marcela; Henríquez, Juan Pablo; Reig, Germán F; Scheu, Jessica; Calderón, Rosario; Alvarez, Alejandra; Brandan, Enrique; Inestrosa, Nibaldo C
Wnt factors are secreted ligands that affect different aspects of the nervous system behavior like neurodevelopment, synaptogenesis and neurodegeneration. In different model systems, Wnt signaling has been demonstrated to be regulated by heparan sulfate proteoglycans (HSPGs). Whether HSPGs modulate Wnt signaling in the context of neuronal behavior is currently unknown. Here we demonstrate that activation of Wnt signaling with the endogenous ligand Wnt-7a results in an increased of neurite outgrowth in the neuroblastoma N2a cell line. Interestingly, heparin induces glycogen synthase kinase-3beta (GSK-3beta) inhibition, beta-catenin stabilization and morphological differentiation in both N2a cells and in rat primary hippocampal neuronal cultures. We also show that heparin modulates Wnt-3a-induced stabilization of beta-catenin. Several extracellular matrix and membrane-attached HSPGs were found to be expressed in both in vitro neuronal models. Changes in the expression of specific HSPGs were observed upon differentiation of N2a cells. Taken together, our findings suggest that HSPGs may modulate canonical Wnt signaling for neuronal morphogenesis.
Hoffman, M S; Mitchell, G S
Acute intermittent hypoxia elicits a form of serotonin-dependent respiratory plasticity known as phrenic long term facilitation (pLTF). Episodic spinal serotonin-2 (5-HT2) receptor activation on or near phrenic motor neurons is necessary for pLTF. A hallmark of pLTF is the requirement for serotonin-dependent synthesis of brain-derived neurotrophic factor (BDNF), and activation of its high affinity receptor, TrkB. Activation of spinal Gs protein-coupled adenosine 2A receptors (GsPCRs) elicits a unique form of long-lasting phrenic motor facilitation (PMF), but via unique mechanisms (BDNF independent TrkB trans-activation).We hypothesized that other GsPCRs elicit PMF, specifically serotonin-7 (5-HT7) receptors, which are expressed in phrenic motor neurons. Cervical spinal (C4) injections of a selective 5-HT7 receptor agonist, AS-19 (10 μM, 5 μl; 3 × 5 min), in anaesthetized, vagotomized and ventilated male Sprague-Dawley rats elicited long-lasting PMF (>120 min), an effect prevented by pretreatment with a 5-HT7 receptor antagonist (SB 269970; 5mM, 7 μl).GsPCR activation 'trans-activates'TrkB by increasing synthesis of an immature TrkB isoform. Spinal injection of a TrkB inhibitor (k252a) and siRNAs that prevent TrkB (but not BDNF) mRNA translation both blocked 5-HT7 agonist-induced PMF, confirming a requirement for TrkB synthesis and activity. k252a affected late PMF (≥ 90 min) only. Spinal inhibition of the PI3K/AKT pathway blocked 5-HT7 agonist-induced PMF, whereas MEK/ERK inhibition delayed, but did not block, PMF. An understanding of signalling mechanisms giving rise to PMF may guide development of novel therapeutic strategies to treat ventilatory control disorders associated with respiratory insufficiency, such as spinal injury and motor neuron disease.
Simmonds, Anna J; Wise, Richard J S; Dhanjal, Novraj S; Leech, Robert
A foreign language (L2) learned after childhood results in an accent. This functional neuroimaging study investigated speech in L2 as a sensory-motor skill. The hypothesis was that there would be an altered response in auditory and somatosensory association cortex, specifically the planum temporale and parietal operculum, respectively, when speaking in L2 relative to L1, independent of rate of speaking. These regions were selected for three reasons. First, an influential computational model proposes that these cortices integrate predictive feedforward and postarticulatory sensory feedback signals during articulation. Second, these adjacent regions (known as Spt) have been identified as a "sensory-motor interface" for speech production. Third, probabilistic anatomical atlases exist for these regions, to ensure the analyses are confined to sensory-motor differences between L2 and L1. The study used functional magnetic resonance imaging (fMRI), and participants produced connected overt speech. The first hypothesis was that there would be greater activity in the planum temporale and the parietal operculum when subjects spoke in L2 compared with L1, one interpretation being that there is less efficient postarticulatory sensory monitoring when speaking in the less familiar L2. The second hypothesis was that this effect would be observed in both cerebral hemispheres. Although Spt is considered to be left-lateralized, this is based on studies of covert speech, whereas overt speech is accompanied by sensory feedback to bilateral auditory and somatosensory cortices. Both hypotheses were confirmed by the results. These findings provide the basis for future investigations of sensory-motor aspects of language learning using serial fMRI studies.
The discovery of directional tuned neurons in the primary motor cortex has advanced motor research in several domains. For instance, in the area of brain machine interface (BMI), researchers have exploited the robust characteristic of tuned motor neurons to allow monkeys to learn control of various machines. In the first chapter of this work we examine whether this phenomena can be observed using the less invasive method of recording electrocorticographic signals (ECoG) from the surface of a human's brain. Our findings reveal that individual ECoG channels contain complex movement information about the neuronal population. While some ECoG channels are tuned to hand movement direction (direction specific channels), others are associated to movement but do not contain information regarding movement direction (non-direction specific channels). More specifically, directionality can vary temporally and by frequency within one channel. In addition, a handful of channels contain no significant information regarding movement at all. These findings strongly suggest that directional and non-directional regions of cortex can be identified with ECoG and provide solutions to decoding movement at the signal resolution provided by ECoG. In the second chapter we examine the influence of movement context on movement reconstruction accuracy. We recorded neuronal signals recorded from electro-corticography (ECoG) during performance of cued- and self-initiated movements. ECoG signals were used to train a reconstruction algorithm to reconstruct continuous hand movement. We found that both cued- and self-initiated movements could be reconstructed with similar accuracy from the ECoG data. However, while an algorithm trained on the cued task could reconstruct performance on a subsequent cued trial, it failed to reconstruct self-initiated arm movement. The same task-specificity was observed when the algorithm was trained with self-initiated movement data and tested on the cued task. Thus
Silber, D H; Sinoway, L I; Leuenberger, U A; Amassian, V E
Single-pulse magnetic coil stimulation (Cadwell MES 10) over the cranium induces without pain an electric pulse in the underlying cerebral cortex. Stimulation over the motor cortex can elicit a muscle twitch. In 10 subjects, we tested whether motor cortical stimulation could also elicit skin sympathetic nerve activity (SSNA; n = 8) and muscle sympathetic nerve activity (MSNA; n = 5) in the peroneal nerve. Focal motor cortical stimulation predictably elicited bursts of SSNA but not MSNA; with successive stimuli, the SSNA responses did not readily extinguish (94% of discharges to the motor cortex evoked SSNA responses) and had predictable latencies [739 +/- 33 (SE) to 895 +/- 13 ms]. The SSNA responses were similar after stimulation of dominant and nondominant sides. Focal stimulation posterior to the motor cortex elicited extinguishable SSNA responses. In three of six subjects, anterior cortical stimulation evoked SSNA responses similar to those seen with motor cortex stimulation but without detectable movement; in the other subjects, anterior stimulation evoked less SSNA discharge than that seen with motor cortex stimulation. Contrasting with motor cortical stimulation, evoked SSNA responses were more readily extinguished with 1) peripheral stimulation that directly elicited forearm muscle activation accompanied by electromyograms similar to those with motor cortical stimulation; 2) auditory stimulation by the click of the energized coil when off the head; and 3) in preliminary experiments, finger afferent stimulation sufficient to cause tingling. Our findings are consistent with the hypothesis that motor cortex stimulation can cause activation of both alpha-motoneurons and SSNA.
Zhemchuzhnikov, M K; Kniazev, A N
The character of motor activity of female crickets Gryllus argentinus Sauss. was studied in norm and under conditions of inactivation of cercal organ at realization of reproductive and protective behavior at various steps of adult ontogenesis (at the 2nd, 7th, and 12th day). There are described and analyzed various forms of female motor reactions on a movable track-ball at presentation f models of male intraspecies call and aggressive signals. The reversible inactivation or cereal receptors was shown to lead to disturbance of mechanisms of realization of normal reproductive behavior in the end of prereproductive and in the beginning of reproductive periods of adult ontogenesis. This is manifested as a significant decrease of reactions of positive phonotaxis in response to presentation of model of the male call signal in individuals with experimental sensory pathology as compared with the control cricket group (norm). No significant differences in portions of typical directed motor reactions were established in norm and under conditions of sensory pathology at presentation of aggressive signal. Thus, we have managed to show that preservation of tympanal organ is the necessary, but not sufficient condition of realization of adequate acoustic reproductive behavior. Only by working together, the distant mechanoreceptor systems (the cereal and the tympanal ones) are able to provide adequate behavior. This confirmed to earlier put forward hypothesis about interaction of distant mechanoreceptor systems and about the existence of the single sensory complex necessary for realization of insect adequate behavior.
Alvarado, José; Sheinman, Michael; Sharma, Abhinav; Mackintosh, Fred C.; Koenderink, Gijsje H.
Living systems naturally exhibit internal driving: active, molecular processes drive non-equilibrium phenomena such as metabolism or migration. Active gels constitute a fascinating class of internally driven matter, in which molecular motors exert localized stresses inside polymer networks. There is evidence that network crosslinking is required to allow motors to induce macroscopic contraction. Yet a quantitative understanding of how network connectivity enables contraction is lacking. Here we show experimentally that myosin motors contract crosslinked actin polymer networks to clusters with a scale-free size distribution. This critical behaviour occurs over an unexpectedly broad range of crosslink concentrations. To understand this robustness, we developed a quantitative model of contractile networks that takes into account network restructuring: motors reduce connectivity by forcing crosslinks to unbind. Paradoxically, to coordinate global contractions, motor activity should be low. Otherwise, motors drive initially well-connected networks to a critical state where ruptures form across the entire network.
Vdovichenko, N D; Timofeeva, O P; Bursian, A V
In rat fetuses at E17-20 with preserved placental circulation with use of mathematical analysis there were revealed value and character of connections of slow wave oscillations of the heart rhythm with motor activity for 30 min of observation. In the software "PowerGraph 3.3.8", normalization and filtration of the studied signals were performed at three frequency diapasons: D1 - 0.02-0.2 Hz (5-50 s), D2 - 0.0083-0.02 Hz (50 s-2 min), and D3 - 0.0017-0.0083 Hz (2-10 min). The EMG curves filtrated by diapasons or piezograms were compared with periodograms in the corresponding diapasons of the heart rhythm variations. In the software "Origin 8.0", quantitative estimation of the degree of intersystemic interrelations for each frequency diapason was performed by Pearson correlation of coefficient, by the correlation connection value, and by the time shift of maximum of cross-correlation function. It has been established that in the frequency D1, regardless of age, the connection of heart rhythm oscillations with motor activity is expressed weakly. In the frequency diapason D2, the connection in most cases is located in the zone of weak and moderate correlations. In the multiminute diapason (D3), the connection is more pronounced. The number of animals that have a significant value of the correlation connection rises. The fetal MA fires in the decasecond diapason in all age groups are accompanied by short-time decelerations of the heart rhythms. In the minute diapason, there is observed a transition from positive connections at E17 and E18 to the negative ones at E19-20. Results of the study are considered in association with age-related changes of ratios of positive and negative oscillations of the heart rhythm change depending on the character of motor activity.
Klein, Pierre-Alexandre; Petitjean, Charlotte; Olivier, Etienne; Duque, Julie
Top-down control is critical to select goal-directed actions in changeable environments, particularly when several options compete for selection. This control system is thought to involve a mechanism that suppresses activation of unwanted response representations. We tested this hypothesis, in humans, by measuring motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in a left finger muscle during motor preparation in an adapted Eriksen flanker task. Subjects reported, by a left or right button-press, the orientation of a left- or right-facing central arrow, flanked by two distractor arrows on each side. Central and peripheral arrows either pointed in the same (congruent trial) or in the opposite direction (incongruent trial). Top-down control was manipulated by changing the probability of congruent and incongruent trials in a given block. In the "mostly incongruent" (MI) blocks, 80% of trials were incongruent, producing a context in which subjects strongly anticipated that they would have to face conflict. In the "mostly congruent" (MC) blocks, 80% of trials were congruent and thus subjects barely anticipated conflict in that context. Thus, we assume that top-down control was stronger in the MI than in the MC condition. Accordingly, subjects displayed a lower error rate and shorter reaction times for the incongruent trials in the MI context than for similar trials in the MC context. More interestingly, we found that top-down control specifically reduced activation of the incompatible motor representation during response selection under high conflict. That is, when the central arrow specified a right hand response, left (non-selected) MEPs became smaller in the MI than in the MC condition, but only for incongruent trials, and this measure was positively correlated with performance. In contrast, MEPs elicited in the non-selected hand during congruent trials, or during all trials in which the left hand was selected, tended to increase
Müller, Katharina; Bacht, Katrin; Prochnow, Denise; Schramm, Stefanie; Seitz, Rüdiger J
The ability to mentally imagine the performance of automatic movements has been well-established being employed in sports and physiotherapy as a tool for motor learning and rehabilitation. This is probably mediated by engagement of the same brain areas as during real motor performance. Here we investigated the effect of hypnotic trance on the cerebral activation pattern engaged in motor imagery in 16 healthy, right-handed subjects using fMRI. Motor imagery as compared with rest was related to activations in the left medial frontal areas (preSMA/SMA), prefrontal- and frontal areas, putamen and inferior parietal areas. When compared with performance of the same movements motor imagery resulted in activation of the left middle frontal cortex, precuneus, and posterior cingulate. Under hypnotic trance there was one extra-activation in the left thalamus which occurred specifically in the motor imagery condition. The regional beta indices were highly correlated among the areas of the cortical-subcortical motor network. Our data accord with the notion that hypnotic trance enhances the motor control circuit engaged in motor imagery by modulating the gating function of the thalamus.
Scharrel, Lara; Ma, Rui; Schneider, René; Jülicher, Frank; Diez, Stefan
Long-range directional transport in cells is facilitated by microtubule-based motor proteins. One example is transport in a nerve cell, where small groups of motor proteins, such as kinesins and cytoplasmic dynein, work together to ensure the supply and clearance of cellular material along the axon. Defects in axonal transport have been linked to Alzheimer's and other neurodegenerative diseases. However, it is not known in detail how multimotor-based cargo transport is impaired if a fraction of the motors are defective. To mimic impaired multimotor transport in vitro, we performed gliding motility assays with varying fractions of active kinesin-1 motors and inactive kinesin-1 motor mutants. We found that impaired transport manifests in multiple motility regimes: 1), a fast-motility regime characterized by gliding at velocities close to the single-molecule velocity of the active motors; 2), a slow-motility regime characterized by gliding at close-to zero velocity or full stopping; and 3), a regime in which fast and slow motilities coexist. Notably, the transition from the fast to the slow regime occurred sharply at a threshold fraction of active motors. Based on single-motor parameters, we developed a stochastic model and a mean-field theoretical description that explain our experimental findings. Our results demonstrate that impaired multimotor transport mostly occurs in an either/or fashion: depending on the ratio of active to inactive motors, transport is either performed at close to full speed or is out of action.
Kadowaki, Akito; Matsukawa, Kanji; Wakasugi, Rie; Nakamoto, Tomoko; Liang, Nan
To examine whether withdrawal of cardiac vagal efferent nerve activity (CVNA) predominantly controls the tachycardia at the start of exercise, the responses of CVNA and cardiac sympathetic efferent nerve activity (CSNA) were directly assessed during fictive motor activity that occurred spontaneously in unanesthetized, decerebrate cats. CSNA abruptly increased by 71 ± 12% at the onset of the motor activity, preceding the tachycardia response. The increase in CSNA lasted for 4-5 s and returned to the baseline, even though the motor activity was not ended. The increase of 6 ± 1 beats/min in heart rate appeared with the same time course of the increase in CSNA. In contrast, CVNA never decreased but increased throughout the motor activity, in parallel with a rise in mean arterial blood pressure (MAP). The peak increase in CVNA was 37 ± 9% at 5 s after the motor onset. The rise in MAP gradually developed to 21 ± 2 mmHg and was sustained throughout the spontaneous motor activity. Partial sinoaortic denervation (SAD) blunted the baroreflex sensitivity of the MAP-CSNA and MAP-CVNA relationship to 22-33% of the control. Although partial SAD blunted the initial increase in CSNA to 53% of the control, the increase in CSNA was sustained throughout the motor activity. In contrast, partial SAD almost abolished the increase in CVNA during the motor activity, despite the augmented elevation of 31 ± 1 mmHg in MAP. Because afferent inputs from both muscle receptors and arterial baroreceptors were absent or greatly attenuated in the partial SAD condition, only central command was operating during spontaneous fictive motor activity in decerebrate cats. Therefore, it is likely that central command causes activation of cardiac sympathetic outflow but does not produce withdrawal of cardiac parasympathetic outflow during spontaneous motor activity.
Baeck, Jong-Su; Kim, Yang-Tae; Seo, Jee-Hye; Ryeom, Hun-Kyu; Lee, Jongmin; Choi, Sung-Mook; Woo, Minjung; Kim, Woojong; Kim, Jin Gu; Chang, Yongmin
Evidence from previous studies has suggested that motor imagery and motor action engage overlapping brain systems. As a result of this observation that motor imagery can activate brain regions associated with actual motor movement, motor imagery is expected to enhance motor skill performance and become an underlying principle for physical training in sports and physical rehabilitation. However, few studies have examined the effects of physical training on motor imagery in beginners. Also, differences in neural networks related to motor imagery before and after training have seldom been studied. In the current study, using functional magnetic resonance imaging (fMRI), we investigated the question of whether motor imagery can reflect plastic changes of neural correlates associated with intensive training. In fact, motor imagery was used in this study as a tool to assess the brain areas involved in shooting and involved in learning of shooting. We discovered that use of motor imagery resulted in recruitment of widely distributed common cortical areas, which were suggested to play a role in generation and maintenance of mental images before and after 90 h of shooting training. In addition to these common areas, brain activation before and after 90 h of shooting practice showed regionally distinct patterns of activity change in subcortical motor areas. That is, basal ganglia showed increased activity after 90 h of shooting practice, suggesting the occurrence of plastic change in association with gains in performance and reinforcement learning. Therefore, our results suggest that, in order to reach a level of expertise, the brain would change through initial reinforcement of preexistent connections during the training period and then use more focused neural correlates through formation of new connections.
Rehfeldt, Florian; Brown, Andre; Engler, Adam; Discher, Dennis
Cells feel their physical microenvironment through their adhesion and respond to it in various ways. Indeed, matrix elasticity can even guide the differentiation of human adult mesenchymal stem cells (MSCs) [Engler et al. Cell 2006]. Sparse cultures of MSCs on elastic collagen--coated substrates that are respectively soft, stiff, or extremely stiff were shown to induce neurogenesis, myogenesis, and osteogenesis. Lineage commitment was evaluated by morphological analysis, protein expression profiles, and transcription microarrays. Differentiation could be completely blocked with a specific non-muscle myosin II (NMM II) inhibitor, suggesting that contractile motor activity is essential for the cells to sense matrix elasticity. Current studies by AFM and near-field fluorescence imaging show that NMM II inhibition in stem cells on rigid glass surfaces promotes actin-rich dendritic outgrowth resembling neurite extension. Dynamic cell studies have been conducted to elucidate the complex molecular interplay of the contractile apparatus in response to selected physical and biochemical stimuli. Additional insight is being gained by using AFM to investigate the local elasticity of the cell's cytoskeletal force sensing machinery.
The objective of this project was to team Aerotech and AlliedSignal FM and T (AS) to develop a cost-efficient process for small-batch, high performance PZT motor production. Aerotech would acquire the basic process expertise in motor fabrication, assembly, and testing from AS. Together, Aerotech and AS were to identify appropriate process improvements, focusing on raw material quality, manufacturing processes, and durability assessment. Aerotech would then design and build a motor in consultation with AS. Aerotech engineering observed motor manufacturing in the AS piezo lab and worked side by side with AS personnel to build and test a prototype motor to facilitate learning the technology. Using information from AS and hands-on experience with the AS motor drive system enabled Aerotech to design and build its own laboratory drive system to operate motors. The team compiled information to establish a potential piezo motor users' list, and an intellectual property search was conducted to understand current patent and IP (intellectual property) status of motor design. Work was initiated to identify and develop an American source for piezo motor elements; however, due to manpower restraints created by the resignation of the AS Ph.D. ceramist responsible for these tasks, the project schedule slipped. The project was subsequently terminated before significant activities were accomplished. AS did, however, provide Aerotech with contacts in Japanese industry that are willing and capable of supplying them with special design motor elements.
Ohlsson, B; Ringström, G; Abrahamsson, H; Simrén, M; Björnsson, E S
The effects of oxytocin in the gastrointestinal tract are unclear. The aim of this study was to examine the effect of infusion of oxytocin on colonic motility and sensitivity in healthy women. Fourteen healthy women were investigated twice. A 6-channel perfusion catheter, with three recording points (2 cm apart) proximally and three recording points distally to a barostat balloon, was inserted to the splenic flexure. An intestinal feeding tube was placed in the mid-duodenum. A 90-min duodenal lipid infusion of 3 kcal min(-1) was administered. Thirty minutes after the start of the lipid infusion, the subject randomly received either 20 or 40 mU min(-1) of oxytocin, or isotonic saline as intravenous infusions for 90 min. Meanwhile, the colonic motility was recorded. During the last 30 min of oxytocin and saline infusion, the visceral sensitivity to balloon distensions was examined. During lipid infusion the number of antegrade contractions per hour was 0.7 +/- 0.3 after saline and 3.9 +/- 1.4 after oxytocin (P = 0.03), indicating more pronounced lumen-occlusive contractile activity after oxytocin administration. Some of these consisted of high-amplitude (> 103 mmHg in amplitude) antegrade contractions. Lipid infusion evoked a decrease of the balloon volume, reflecting increased colonic tone, but there was no difference between saline and oxytocin. Sensory thresholds did not differ significantly between saline and oxytocin. Infusion of oxytocin stimulates antegrade peristaltic contractions in stimulated colon in healthy women. The effects of oxytocin on colonic motor activity deserve to be further explored, especially in patients with colonic peristaltic dysfunction.
Mendelsohn, Alana I; Dasen, Jeremy S; Jessell, Thomas M
The establishment of spinal motor neuron subclass diversity is achieved through developmental programs that are aligned with the organization of muscle targets in the limb. The evolutionary emergence of digits represents a specialized adaptation of limb morphology, yet it remains unclear how the specification of digit-innervating motor neuron subtypes parallels the elaboration of digits. We show that digit-innervating motor neurons can be defined by selective gene markers and distinguished from other LMC neurons by the expression of a variant Hox gene repertoire and by the failure to express a key enzyme involved in retinoic acid synthesis. This divergent developmental program is sufficient to induce the specification of digit-innervating motor neurons, emphasizing the specialized status of digit control in the evolution of skilled motor behaviors. Our findings suggest that the emergence of digits in the limb is matched by distinct mechanisms for specifying motor neurons that innervate digit muscles.
Pinkoviezky, I; Gov, N S
Molecular motors are involved in key transport processes in the cell. Many of these motors can switch from an active to a nonactive state, either spontaneously or depending on their interaction with other molecules. When active, the motors move processively along the filaments, while when inactive they are stationary. We treat here the simple case of spontaneously switching motors, between the active and inactive states, along an open linear track. We use our recent analogy with vehicular traffic, where we go beyond the mean-field description. We map the phase diagram of this system, and find that it clearly breaks the symmetry between the different phases, as compared to the standard total asymmetric exclusion process. We make several predictions that may be testable using molecular motors in vitro and in living cells.
Irwin, Michael R.; Wang, Minge; Ribeiro, Denise; Cho, Hyong Jin; Olmstead, Richard; Breen, Elizabeth Crabb; Martinez-Maza, Otoniel; Cole, Steve
Background Accumulating evidence suggests that sleep disturbance is associated with inflammation and related disorders including cardiovascular disease, arthritis, and diabetes mellitus. This study was undertaken to test the effects of sleep loss on activation of nuclear factor (NF) -κB, a transcription factor that serves a critical role in the inflammatory signaling cascade. Methods In 14 healthy adults (7 females; 7 males), peripheral blood mononuclear cell NF-κB was repeatedly assessed, along with enumeration of lymphocyte subpopulations, in the morning after baseline sleep, partial sleep deprivation (awake from 23:00 h to 03:00 h), and recovery sleep. Results In the morning after a night of sleep loss, mononuclear cell NF-κB activation was significantly greater compared with morning levels following uninterrupted baseline or recovery sleep, in which the response was found in females but not in males. Conclusions These results identify NF-κB activation as a molecular pathway by which sleep disturbance may influence leukocyte inflammatory gene expression and the risk of inflammation-related disease. PMID:18561896
Gonschorek, A. S.; Lu, L. L.; Halliwill, J. R.; Beightol, L. A.; Taylor, J. A.; Painter, J. A.; Warzel, H.; Eckberg, D. L.
Although humans hold great advantages over other species as subjects for biomedical research, they also bring major disadvantages. One is that among the many rhythmic physiological signals that can be recorded, there is no sure way to know which individual change precedes another, or which change represents cause and which represents effect. In an attempt to deal with the inherent complexity of research conducted in intact human subjects, we developed and used a structural equation model to analyse responses of healthy young men to pharmacological changes of arterial pressure and graded inspiratory resistance, before and after vagomimetic atropine. Our model yielded a good fit of the experimental data, with a system weighted R2 of 0.77, and suggested that our treatments exerted both direct and indirect influences on the variables we measured. Thus, infusions of nitroprusside and phenylephrine exerted all of their direct effects by lowering and raising arterial pressure; the changes of R-R intervals, respiratory sinus arrhythmia and arterial pressure fluctuations that these drugs provoked, were indirect consequences of arterial pressure changes. The only direct effect of increased inspiratory resistance was augmentation of arterial pressure fluctuations. These results may provide a new way to disentangle and understand responses of intact human subjects to experimental forcings. The principal new insight we derived from our modelling is that respiratory gating of vagal-cardiac motor neurone firing is nearly maximal at usual levels of arterial pressure and inspiratory motor neurone activity.
Sorrell, Howard M.
The article describes tasks that promote perceptual motor coordination in handicapped students. An introductory section provides suggestions for implementation and charts the activities in terms of emphasis on visual tracking, visual discrimination and/or copying of forms, spatial body perception, fine motor coordination, tactile discrimination,…
This guide for persons working with young children with gross motor delays is designed to be used in the assessment of gross motor abilities, the detection and identification of delays and the planning and implementation of appropriate Individual Activity Plans (IAP) for correcting the delays. Observation guidelines in the form of questions (Can…
Weber, Jeffrey K.; Shukla, Diwakar; Pande, Vijay S.
Life is fundamentally a nonequilibrium phenomenon. At the expense of dissipated energy, living things perform irreversible processes that allow them to propagate and reproduce. Within cells, evolution has designed nanoscale machines to do meaningful work with energy harnessed from a continuous flux of heat and particles. As dictated by the Second Law of Thermodynamics and its fluctuation theorem corollaries, irreversibility in nonequilibrium processes can be quantified in terms of how much entropy such dynamics produce. In this work, we seek to address a fundamental question linking biology and nonequilibrium physics: can the evolved dissipative pathways that facilitate biomolecular function be identified by their extent of entropy production in general relaxation processes? We here synthesize massive molecular dynamics simulations, Markov state models (MSMs), and nonequilibrium statistical mechanical theory to probe dissipation in two key classes of signaling proteins: kinases and G-protein–coupled receptors (GPCRs). Applying machinery from large deviation theory, we use MSMs constructed from protein simulations to generate dynamics conforming to positive levels of entropy production. We note the emergence of an array of peaks in the dynamical response (transient analogs of phase transitions) that draw the proteins between distinct levels of dissipation, and we see that the binding of ATP and agonist molecules modifies the observed dissipative landscapes. Overall, we find that dissipation is tightly coupled to activation in these signaling systems: dominant entropy-producing trajectories become localized near important barriers along known biological activation pathways. We go on to classify an array of equilibrium and nonequilibrium molecular switches that harmonize to promote functional dynamics. PMID:26240354
Abdelghani, Mohamed N.; Abbas, James J.; Horch, Kenneth W.; Jung, Ranu
Decoding motor intent from recorded neural signals is essential for the development of effective neural-controlled prostheses. To facilitate the development of online decoding algorithms we have developed a software platform to simulate neural motor signals recorded with peripheral nerve electrodes, such as longitudinal intrafascicular electrodes (LIFEs). The simulator uses stored motor intent signals to drive a pool of simulated motoneurons with various spike shapes, recruitment characteristics, and firing frequencies. Each electrode records a weighted sum of a subset of simulated motoneuron activity patterns. As designed, the simulator facilitates development of a suite of test scenarios that would not be possible with actual data sets because, unlike with actual recordings, in the simulator the individual contributions to the simulated composite recordings are known and can be methodically varied across a set of simulation runs. In this manner, the simulation tool is suitable for iterative development of real-time decoding algorithms prior to definitive evaluation in amputee subjects with implanted electrodes. The simulation tool was used to produce data sets that demonstrate its ability to capture some features of neural recordings that pose challenges for decoding algorithms. PMID:25452711
Eichhammer, Peter; Langguth, Berthold; Müller, Jürgen; Hajak, Göran
Transcranial magnetic stimulation as mapping method offers the possibility to measure aspects of motor cortex excitability painlessly and non-invasively. Using this neurophysiological tool, new insights into the effects of central-acting drugs are possible. Particularly striking seems to be the potential of this approach to gain new insights into neurobiological processes associated with neuropsychiatric diseases like schizophrenia or major depression. In combination with genetic aspects, TMS is able to bridge the gap between molecular research and clinical approach.
Jana, Biman; Onuchic, José N
A structure-based model of myosin motor is built in the same spirit of our early work for kinesin-1 and Ncd towards physical understanding of its mechanochemical cycle. We find a structural adaptation of the motor head domain in post-powerstroke state that signals faster ADP release from it compared to the same from the motor head in the pre-powerstroke state. For dimeric myosin, an additional forward strain on the trailing head, originating from the postponed powerstroke state of the leading head in the waiting state of myosin, further increases the rate of ADP release. This coordination between the two heads is the essence of the processivity of the cycle. Our model provides a structural description of the powerstroke step of the cycle as an allosteric transition of the converter domain in response to the Pi release. Additionally, the variation in structural elements peripheral to catalytic motor domain is the deciding factor behind diverse directionalities of myosin motors (myosin V & VI). Finally, we observe that there are general rules for functional molecular motors across the different families. Allosteric structural adaptation of the catalytic motor head in different nucleotide states is crucial for mechanochemistry. Strain-mediated coordination between motor heads is essential for processivity and the variation of peripheral structural elements is essential for their diverse functionalities.
Jana, Biman; Onuchic, José N.
A structure-based model of myosin motor is built in the same spirit of our early work for kinesin-1 and Ncd towards physical understanding of its mechanochemical cycle. We find a structural adaptation of the motor head domain in post-powerstroke state that signals faster ADP release from it compared to the same from the motor head in the pre-powerstroke state. For dimeric myosin, an additional forward strain on the trailing head, originating from the postponed powerstroke state of the leading head in the waiting state of myosin, further increases the rate of ADP release. This coordination between the two heads is the essence of the processivity of the cycle. Our model provides a structural description of the powerstroke step of the cycle as an allosteric transition of the converter domain in response to the Pi release. Additionally, the variation in structural elements peripheral to catalytic motor domain is the deciding factor behind diverse directionalities of myosin motors (myosin V & VI). Finally, we observe that there are general rules for functional molecular motors across the different families. Allosteric structural adaptation of the catalytic motor head in different nucleotide states is crucial for mechanochemistry. Strain-mediated coordination between motor heads is essential for processivity and the variation of peripheral structural elements is essential for their diverse functionalities. PMID:27494025
Chakrabarty, S; Friel, K M; Martin, J H
Motor cortex (M1) activity between postnatal weeks 5 and 7 is essential for normal development of the corticospinal tract (CST) and visually guided movements. Unilateral reversible inactivation of M1, by intracortical muscimol infusion, during this period permanently impairs development of the normal dorsoventral distribution of CST terminations and visually guided motor skills. These impairments are abrogated if this M1 inactivation is followed by inactivation of the contralateral, initially active M1, from weeks 7 to 11 (termed alternate inactivation). This later period is when the M1 motor representation normally develops. The purpose of this study was to determine the effects of alternate inactivation on the motor representation of the initially inactivated M1. We used intracortical microstimulation to map the left M1 1 to 2 mo after the end of left M1 muscimol infusion. We compared representations in the unilateral inactivation and alternate inactivation groups. Alternate inactivation converted the sparse proximal M1 motor representation produced by unilateral inactivation to a complete and high-resolution proximal-distal representation. The motor map was restored by week 11, the same age that our present and prior studies demonstrated that alternate inactivation restored CST spinal connectivity. Thus M1 motor map developmental plasticity closely parallels plasticity of CST spinal terminations. After alternate inactivation reestablished CST connections and the motor map, an additional 3 wk was required for motor skill recovery. Since motor map recovery preceded behavioral recovery, our findings suggest that the representation is necessary for recovering motor skills, but additional time, or experience, is needed to learn to take advantage of the restored CST connections and motor map.
Vogt, M. C.
Many industrial and environmental processes, including bioremediation, would benefit from the feedback and control information provided by a local multi-analyte chemical sensor. For most processes, such a sensor would need to be rugged enough to be placed in situ for long-term remote monitoring, and inexpensive enough to be fielded in useful numbers. The multi-analyte capability is difficult to obtain from common passive sensors, but can be provided by an active device that produces a spectrum-type response. Such new active gas microsensor technology has been developed at Argonne National Laboratory. The technology couples an electrocatalytic ceramic-metallic (cermet) microsensor with a voltammetric measurement technique and advanced neural signal processing. It has been demonstrated to be flexible, rugged, and very economical to produce and deploy. Both narrow interest detectors and wide spectrum instruments have been developed around this technology. Much of this technology's strength lies in the active measurement technique employed. The technique involves applying voltammetry to a miniature electrocatalytic cell to produce unique chemical ''signatures'' from the analytes. These signatures are processed with neural pattern recognition algorithms to identify and quantify the components in the analyte. The neural signal processing allows for innovative sampling and analysis strategies to be employed with the microsensor. In most situations, the whole response signature from the voltammogram can be used to identify, classify, and quantify an analyte, without dissecting it into component parts. This allows an instrument to be calibrated once for a specific gas or mixture of gases by simple exposure to a multi-component standard rather than by a series of individual gases. The sampled unknown analytes can vary in composition or in concentration, the calibration, sensing, and processing methods of these active voltammetric microsensors can detect, recognize, and
Camden, Andi; Buliung, Ron; Rothman, Linda; Macarthur, Colin
Objective To determine whether pedestrian countdown signals (PCS) reduce pedestrian–motor vehicle collisions in the city of Toronto, Canada. Methods A quasi-experimental study design was used to evaluate the effect of PCS on the number of pedestrian–motor vehicle collisions in the city of Toronto, from January 2000 to December 2009. Each intersection acted as its own control. We compared the number of pedestrian–motor vehicle collisions per intersection-month before and after the intervention. Stratified models were used to evaluate effect modification by pedestrian age, injury severity and location (urban vs inner suburbs). Poisson regression analysis with repeated measures (generalised estimating equations) was used to estimate the RR and 95% CI. Results The analysis included 9262 pedestrian–motor vehicle collisions at 1965 intersections. The RR of collisions after PCS installation was 1.014 (95% CI 0.958 to 1.073), indicating no statistically significant effect of PCS on collisions. There was no evidence to suggest effect modification between PCS and collisions by age, injury severity or location. Conclusion The installation of PCS at 1965 signalised intersections in Toronto did not reduce the number of pedestrian–motor vehicle collisions at these intersections. PMID:22157206
Molecular motors, by turning chemical energy into mechanical work, are responsible for active cellular processes. Often groups of these motors work together to perform their biological role. Motors in an ensemble are coupled and exhibit complex emergent behavior. Although large motor ensembles can be modeled with partial differential equations (PDEs) by assuming that molecules function independently of their neighbors, this assumption is violated when motors are coupled locally. It is therefore unclear how to describe the ensemble behavior of the locally coupled motors responsible for biological processes such as calcium-dependent skeletal muscle activation. Here we develop a theory to describe locally coupled motor ensembles and apply the theory to skeletal muscle activation. The central idea is that a muscle filament can be divided into two phases: an active and an inactive phase. Dynamic changes in the relative size of these phases are described by a set of linear ordinary differential equations (ODEs). As the dynamics of the active phase are described by PDEs, muscle activation is governed by a set of coupled ODEs and PDEs, building on previous PDE models. With comparison to Monte Carlo simulations, we demonstrate that the theory captures the behavior of locally coupled ensembles. The theory also plausibly describes and predicts muscle experiments from molecular to whole muscle scales, suggesting that a micro- to macroscale muscle model is within reach.
Deloose, Eveline; Tack, Jan
During the fasting state the upper gastrointestinal tract exhibits a specific periodic migrating contraction pattern that is known as the migrating motor complex (MMC). Three different phases can be distinguished during the MMC. Phase III of the MMC is the most active of the three and can start either in the stomach or small intestine. Historically this pattern was designated to be the housekeeper of the gut since disturbances in the pattern were associated with small intestinal bacterial overgrowth; however, its role in the involvement of hunger sensations was already hinted in the beginning of the 20th century by both Cannon (Cannon W, Washburn A. Am J Physiol 29: 441-454, 1912) and Carlson (Carlson A. The Control of Hunger in Health and Disease. Chicago, IL: Univ. of Chicago Press, 1916). The discovery of motilin in 1973 shed more light on the control mechanisms of the MMC. Motilin plasma levels fluctuate together with the phases of the MMC and induce phase III contractions with a gastric onset. Recent research suggests that these motilin-induced phase III contractions signal hunger in healthy subjects and that this system is disturbed in morbidly obese patients. This minireview describes the functions of the MMC in the gut and its regulatory role in controlling hunger sensations.
Rietschel, Jeremy C; Miller, Matthew W; Gentili, Rodolphe J; Goodman, Ronald N; McDonald, Craig G; Hatfield, Bradley D
Excessive increases in task difficulty typically result in marked attenuation of cognitive-motor performance. The psychomotor efficiency hypothesis suggests that poor performance is mediated by non-essential neural activity and cerebral cortical networking (inefficient cortical dynamics). This phenomenon may underlie the inverse relationship between excessive task difficulty and performance. However, investigation of the psychomotor efficiency hypothesis as it relates to task difficulty has not been conducted. The present study used electroencephalography (EEG) to examine cerebral cortical dynamics while participants were challenged with both Easy and Hard conditions during a cognitive-motor task (Tetris(®)). In accord with the psychomotor efficiency hypothesis, it was predicted that with increases in task difficulty, participants would demonstrate greater 'neural effort,' as indexed by EEG spectral power and cortical networking (i.e., EEG coherence) between the premotor (motor planning) region and sensory, executive, and motor regions. Increases in neural activation and cortical networking were observed during the Hard condition relative to the Easy condition, thus supporting the psychomotor efficiency hypothesis. To further determine the unique contributions of cognitive versus sensory-motor demands, a control experiment was conducted in which cognitive demand was increased while sensory-motor demand was held constant. This experiment revealed that regionally specific neural activation was influenced by changes in cognitive demand, whereas cortical networking to the motor planning region was sensitive only to changes in sensory-motor demand. Crucially, the present study is the first, to our knowledge, to characterize the separate impact of cognitive versus sensory-motor demands on cerebral cortical dynamics. The findings further inform the dynamics of the cortical processes that underlie the quality of cognitive-motor performance particularly with regard to task
...) One on the traffic side of and 4 paces (approximately 3 meters or 10 feet) from the stopped commercial motor vehicle in the direction of approaching traffic; (ii) One at 40 paces (approximately 30 meters or... paces (approximately 30 meters or 100 feet) from the stopped commercial motor vehicle in the center...
...) One on the traffic side of and 4 paces (approximately 3 meters or 10 feet) from the stopped commercial motor vehicle in the direction of approaching traffic; (ii) One at 40 paces (approximately 30 meters or... paces (approximately 30 meters or 100 feet) from the stopped commercial motor vehicle in the center...
Cauraugh, James H; Kim, Sangbum
Chronic cerebrovascular accident individuals with partial paralysis in an upper extremity typically demonstrate difficulty in voluntarily controlling movement initiation. This study investigated patterns of electromyogram (EMG) activation levels while stroke subjects voluntarily initiated their impaired wrist and finger extensor muscles. Twenty subjects were randomly assigned to either a unilateral movement/stimulation group or a bilateral movement/stimulation group. Participants completed 4 days (6 h over 2 weeks) of active neuromuscular stimulation (i.e., 5 s/trial, 90 trials/day, biphasic waveform) on the wrist and finger extensors according to group assignments. The EMG activation levels were analyzed with a three-factor mixed design Motor recovery protocol x Session block x Trial block (2 x 2 x 3) ANOVA with repeated measures on the second and third factors. This robust analysis revealed higher EMG activation levels for the coupled bilateral movement/stimulation group than the unilateral movement/stimulation group. In addition, higher muscle activation levels were found for the second session block as well as trial blocks 2 and 3. Overall, these findings indicated improved motor capabilities of the impaired muscles as evidenced by the higher voluntary EMG activation levels.
Frandsen, Rune; Nikolic, Miki; Zoetmulder, Marielle; Kempfner, Lykke; Jennum, Poul
Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterized by dream enactment and REM sleep without atonia. Atonia is evaluated on the basis of visual criteria, but there is a need for more objective, quantitative measurements. We aimed to define and optimize a method for establishing baseline and all other parameters in automatic quantifying submental motor activity during REM sleep. We analysed the electromyographic activity of the submental muscle in polysomnographs of 29 patients with idiopathic RBD (iRBD), 29 controls and 43 Parkinson's (PD) patients. Six adjustable parameters for motor activity were defined. Motor activity was detected and quantified automatically. The optimal parameters for separating RBD patients from controls were investigated by identifying the greatest area under the receiver operating curve from a total of 648 possible combinations. The optimal parameters were validated on PD patients. Automatic baseline estimation improved characterization of atonia during REM sleep, as it eliminates inter/intra-observer variability and can be standardized across diagnostic centres. We found an optimized method for quantifying motor activity during REM sleep. The method was stable and can be used to differentiate RBD from controls and to quantify motor activity during REM sleep in patients with neurodegeneration. No control had more than 30% of REM sleep with increased motor activity; patients with known RBD had as low activity as 4.5%. We developed and applied a sensitive, quantitative, automatic algorithm to evaluate loss of atonia in RBD patients.
Godec, Aljaž; Metzler, Ralf
Molecular signalling in living cells occurs at low copy numbers and is thereby inherently limited by the noise imposed by thermal diffusion. The precision at which biochemical receptors can count signalling molecules is intimately related to the noise correlation time. In addition to passive thermal diffusion, messenger RNA and vesicle-engulfed signalling molecules can transiently bind to molecular motors and are actively transported across biological cells. Active transport is most beneficial when trafficking occurs over large distances, for instance up to the order of 1 metre in neurons. Here we explain how intermittent active transport allows for faster equilibration upon a change in concentration triggered by biochemical stimuli. Moreover, we show how intermittent active excursions induce qualitative changes in the noise in effectively one-dimensional systems such as dendrites. Thereby they allow for significantly improved signalling precision in the sense of a smaller relative deviation in the concentration read-out by the receptor. On the basis of linear response theory we derive the exact mean field precision limit for counting actively transported molecules. We explain how intermittent active excursions disrupt the recurrence in the molecular motion, thereby facilitating improved signalling accuracy. Our results provide a deeper understanding of how recurrence affects molecular signalling precision in biological cells and novel medical-diagnostic devices.
This paper intend to propose some new results related with computer aided monitoring of transient regimes on machine-tools based on the evolution of active electrical power absorbed by the electric motor used to drive the main kinematic chains and the evolution of rotational speed and acceleration of the main shaft. The active power is calculated in numerical format using the evolution of instantaneous voltage and current delivered by electrical power system to the electric motor. The rotational speed and acceleration of the main shaft are calculated based on the signal delivered by a sensor. Three real-time analogic signals are acquired with a very simple computer assisted setup which contains a voltage transformer, a current transformer, an AC generator as rotational speed sensor, a data acquisition system and a personal computer. The data processing and analysis was done using Matlab software. Some different transient regimes were investigated; several important conclusions related with the advantages of this monitoring technique were formulated. Many others features of the experimental setup are also available: to supervise the mechanical loading of machine-tools during cutting processes or for diagnosis of machine-tools condition by active electrical power signal analysis in frequency domain.
Hu, X. L.; Tong, K. Y.; Hung, L. K.
The refractory period of a motor unit is an important mechanism that regulates the motor unit firing, and its variation has been found in many physiological cases. In this study, a new observation that an increase in the motor unit refractoriness results in an enhancement of oscillations, or ripple effects, in the motor unit output power density spectra (PDS) has been identified and studied. The effects of the refractoriness variation on the PDS of motor unit firing were investigated on three levels: theoretical modeling, simulation and electromyographic (EMG) experimentation on human subjects. Both theoretical modeling and simulation showed the enhanced oscillations, ripple effects, in MUAPT PDS, given the increase in the refractoriness. It was also found that the extent of the increment in output PDS oscillation could be related to the motor unit size and the mean firing rate of the stimulation. A needle EMG experiment on biceps brachii muscles of five healthy human subjects was carried out during isometric contraction at 20% maximum voluntary contraction (MVC) for 20 s with a fatigue effort proceeded by MVC. The increased oscillations in the PDS of the real MUAPTs were observed with the rising of the motor unit refractoriness due to fatigue. The study gives new information for EMG spectra interpretation, and also provides a potential method for accessing neuromuscular transmission failure (NTF) due to fatigue during voluntary contraction.
Vasquez, Claudia G; Heissler, Sarah M; Billington, Neil; Sellers, James R; Martin, Adam C
Non-muscle cell contractility is critical for tissues to adopt shape changes. Although, the non-muscle myosin II holoenzyme (myosin) is a molecular motor that powers contraction of actin cytoskeleton networks, recent studies have questioned the importance of myosin motor activity cell and tissue shape changes. Here, combining the biochemical analysis of enzymatic and motile properties for purified myosin mutants with in vivo measurements of apical constriction for the same mutants, we show that in vivo constriction rate scales with myosin motor activity. We show that so-called phosphomimetic mutants of the Drosophila regulatory light chain (RLC) do not mimic the phosphorylated RLC state in vitro. The defect in the myosin motor activity in these mutants is evident in developing Drosophila embryos where tissue recoil following laser ablation is decreased compared to wild-type tissue. Overall, our data highlights that myosin activity is required for rapid cell contraction and tissue folding in developing Drosophila embryos.
The acute neurobehavioral effects of acetylcholinesterase-inhibiting pesticides are primarily due to overstimulation of the cholinergic system. Lowered motor activity levels represent a sensitive endpoint with which to monitor functional changes in laboratory animals exposed to ...
Kameyama, Márcia; Siqueira, Fernanda A; Garcia-Mijares, Miriam; Silva, Luiz F; Silva, Maria T A
A new approach for the synthesis of indatraline was developed using as the key step an iodine(III)-mediated ring contraction of a 1,2-dihydronaphthalene derivative. Behavioral tests were conducted to evaluate the effect of indatraline and of its precursor indanamide on the motor activity of Wistar rats. Specific indexes for ambulation, raising and stereotypy were computed one, two and three hours after i.p. drug administration. Indatraline effects on motor activity lasted for at least three hours. On the other hand, no significant differences in motor activity were observed using indanamide. The results suggest that indatraline has a long lasting effect on motor activity and add evidence in favor of the potential use of that compound as a substitute in cocaine addiction.
Anderson, William S; Weiss, Nirit; Lawson, Herman Christopher; Ohara, Shinji; Rowland, Lance; Lenz, Frederick A
Functional imaging studies show that motor imagery activates multiple structures in the human forebrain. We now show that phantom movements in an amputee and imagined movements in intact individuals elicit responses from neurons in several human thalamic nuclei. These include the somatic sensory nucleus receiving input from the periphery (ventral caudal), and the motor nuclei receiving input from the cerebellum [ventral intermediate (Vim)] and the basal ganglia [ventral oral posterior (Vop)]. Seven neurons in the amputee showed phantom movement-related activity (three Vim, two Vop, and two ventral caudal). In addition, seven neurons in a group of three controls showed motor imagery-related activity (four Vim and three Vop). These studies were performed during single neuron recording sessions in patients undergoing therapeutic treatment of phantom pain, tremor, and chronic pain conditions by thalamic stimulation. The activity of neurons in these sensory and motor nuclei, respectively, may encode the expected sensory consequences and the dynamics of planned movements.
Kevenaar, Josta T; Bianchi, Sarah; van Spronsen, Myrrhe; Olieric, Natacha; Lipka, Joanna; Frias, Cátia P; Mikhaylova, Marina; Harterink, Martin; Keijzer, Nanda; Wulf, Phebe S; Hilbert, Manuel; Kapitein, Lukas C; de Graaff, Esther; Ahkmanova, Anna; Steinmetz, Michel O; Hoogenraad, Casper C
Kinesin motor proteins play a fundamental role for normal neuronal development by controlling intracellular cargo transport and microtubule (MT) cytoskeleton organization. Regulating kinesin activity is important to ensure their proper functioning, and their misregulation often leads to severe human neurological disorders. Homozygous nonsense mutations in kinesin-binding protein (KBP)/KIAA1279 cause the neurological disorder Goldberg-Shprintzen syndrome (GOSHS), which is characterized by intellectual disability, microcephaly, and axonal neuropathy. Here, we show that KBP regulates kinesin activity by interacting with the motor domains of a specific subset of kinesins to prevent their association with the MT cytoskeleton. The KBP-interacting kinesins include cargo-transporting motors such as kinesin-3/KIF1A and MT-depolymerizing motor kinesin-8/KIF18A. We found that KBP blocks KIF1A/UNC-104-mediated synaptic vesicle transport in cultured hippocampal neurons and in C. elegans PVD sensory neurons. In contrast, depletion of KBP results in the accumulation of KIF1A motors and synaptic vesicles in the axonal growth cone. We also show that KBP regulates neuronal MT dynamics by controlling KIF18A activity. Our data suggest that KBP functions as a kinesin inhibitor that modulates MT-based cargo motility and depolymerizing activity of a subset of kinesin motors. We propose that misregulation of KBP-controlled kinesin motors may represent the underlying molecular mechanism that contributes to the neuropathological defects observed in GOSHS patients.
South Euclid - Lyndhurst City Schools, Lyndhurst, OH.
This document has been prepared as part of a kindergarten perceptual-training program of the South Euclid-Lyndhurst City School District near Cleveland, Ohio. The guide contains information on training and procedures related to perceptual-motor learning. This information is structured primarily into 150 lesson plans, devised as 30-minute sessions…
Joshi, Dinesh C; Tewari, Bhanu P; Singh, Mahendra; Joshi, Preeti G; Joshi, Nanda B
suppressed the ROS formation only in motor neurons. It appears that activation of cytoplasmic nNOS leads to ROS formation in both types of spinal neurons but mitochondria is the major source of ROS in motor neurons. Spinal neurons exhibited a significant time dependent fall in glutathione (GSH) level. The GSH level in motor neurons did not recover even at 24h after AMPA exposure, whereas the other spinal neurons exhibited a tendency to maintain the GSH after a certain level suggesting that the oxidative stress is arrested in other spinal neurons but it continues to increase in motor neurons. Thus our results demonstrate that upon AMPA receptor stimulation the motor neurons employ some additional pathways for regulation of mitochondrial calcium and oxidative stress as compared to other spinal neurons. It is suggested that such differential signaling mechanisms in motor neurons could be crucial for their selective vulnerability to excitotoxicity.
Khodaverdi, Zeinab; Bahram, Abbas; Stodden, David; Kazemnejad, Anoshirvan
The purpose of this study was to investigate whether perceived motor competence and components of health-related physical fitness mediated the relationship between actual motor competence and physical activity in 8- to 9-year-old Iranian girls. A convenience sample of 352 girls (mean age = 8.7, SD = 0.3 years) participated in the study. Actual motor competence, perceived motor competence and children's physical activity were assessed using the Test of Gross Motor Development-2, the physical ability sub-scale of Marsh's Self-Description Questionnaire and Physical Activity Questionnaire for Older Children, respectively. Body mass index, the 600 yard run/walk, curl-ups, push-ups, and back-saver sit and reach tests assessed health-related physical fitness. Preacher & Hayes (2004) bootstrap method was used to assess the potential mediating effects of fitness and perceived competence on the direct relationship between actual motor competence and physical activity. Regression analyses revealed that aerobic fitness (b = .28, 95% CI = [.21, .39]), as the only fitness measure, and perceived competence (b = .16, 95% CI = [.12, .32]) were measures that mediated the relationship between actual motor competence and physical activity with the models. Development of strategies targeting motor skill acquisition, children's self-perceptions of competence and cardiorespiratory fitness should be targeted to promote girls' moderate-to-vigorous physical activity.
Cirillo, John; Lavender, Andrew P; Ridding, Michael C; Semmler, John G
Recent evidence indicates that regular physical activity enhances brain plasticity (i.e. the ability to reorganise neural connections) and improves neurocognitive function. However, the effect of regular physical activity on human motor cortex function is unknown. The purpose of this study was to examine motor cortex plasticity for a small hand muscle in highly active and sedentary individuals. Electromyographic recordings were obtained from the left abductor pollicis brevis (APB) muscle of 14 active and 14 sedentary subjects (aged 18-38 yrs). The extent of physical activity was assessed by questionnaire, where the physically active subjects performed >150 min per day moderate-to-vigorous aerobic activity on at least 5 days per week, whereas the sedentary group performed <20 min per day of physical activity on no more than 3 days per week. Transcranial magnetic stimulation (TMS) of the right hemisphere was used to assess changes in APB motor-evoked potentials (MEPs), input-output curve (IO curve), short-interval intracortical inhibition (SICI) and cortical silent period (CSP). Neuroplastic changes were induced using paired-associative stimulation (PAS), which consisted of 90 paired stimuli (0.05 Hz for 30 min) of median nerve electrical stimulation at the wrist followed 25 ms later by TMS to the hand area of motor cortex. The IO curve slope was 35% steeper in individuals with increased physical activity (combined before and after PAS, P < 0.05), suggesting increased motor cortex excitability, although there was no difference in SICI or CSP between groups. PAS induced an increase in MEP amplitude in the physically active subjects (54% increase compared with before, P < 0.01), but no significant facilitation in the sedentary subjects. We conclude that participation in regular physical activity may offer global benefits to motor cortex function that enhances neuroplasticity, which could improve motor learning and neurorehabilitation in physically active individuals.
stress . It is possible that the correlated activity between EEG and EMG is used for “fine-tuning” brain activity during the performance of fine motor...brain and muscle during simple fine motor performance under stress after high-intensity physical exertion. Healthy young adults were assigned to...leg resistance exercise. Oscillations in EEG and corticomuscular coherence in beta band both tended to decrease 1. REPORT DATE (DD-MM-YYYY) 4. TITLE
Robles-Mendoza, Cecilia; Zúñiga-Lagunes, Sebastian R; Ponce de León-Hill, Claudia A; Hernández-Soto, Jesús; Vanegas-Pérez, Cecilia
The axolotl Ambystoma mexicanum is a neotenic salamander considered a good biological model due to its ability to regenerate limbs, tail, brain and heart cells. Nevertheless, severe reduction of A. mexicanum wild populations in the lacustrine area of Xochimilco, the natural habitat of the axolotl, could be related to several environmental pressures as the presence of organophosphate pesticides (OPPs), intensively applied in agricultural activities in Xochimilco. Thus the aim of this study was to evaluate the effect of environmentally realistic chlorpyrifos (CPF) concentrations, a OPP commonly used in this zone, on esterases activity (acetylcholinesterase and carboxylesterase) and bioconcentration of CPF and to relate them with the motor activity of A. mexicanum juveniles. Axolotls were exposed 48 h to 0.05 and 0.1mg CPF/L, and the responses were evaluated at the end of the CPF exposure. Results suggest that CPF is bioconcentrated into axolotls and that the CPF internal concentrations are related with the observed inhibition activity of AChE (>50%) and CbE (≈ 50%). CPF concentration responsible of the inhibition of the 50% of AChE activity (IC50) was estimated in 0.04 mg CPF/L; however IC50 for CbE activity was not possible to calculate since inhibition levels were lower than 50%, results that suggest a higher resistance of CbE enzymatic activity to CPF. However, motor activity was a more sensitive endpoint to CPF poisoning since time that axolotls spent active and walking, frequency and speed of swimming, frequency of prey attack were reduced >90% of control groups. The motor activity alterations in the axolotl could be related with the registered esterases inhibition. Thus important alterations on axolotls were identified even at short time and low concentrations of CPF exposure. Also, it was possible to link biochemical responses as esterases activity with higher levels of biological organization as behavior. This study provides tools for the regulation of the
Donovan, Edward R; Keeney, Brooke K; Kung, Eric; Makan, Sirish; Wild, J Martin; Altshuler, Douglas L
Flying animals exhibit profound transformations in anatomy, physiology, and neural architecture. Although much is known about adaptations in the avian skeleton and musculature, less is known about neuroanatomy and motor unit integration for bird flight. Hummingbirds are among the most maneuverable and specialized of vertebrate fliers, and two unusual neuromuscular features have been previously reported: (1) the pectoralis major has a unique distribution pattern of motor end plates (MEPs) compared with all other birds and (2) electromyograms (EMGs) from the hummingbird's pectoral muscles, the pectoralis major and the supracoracoideus, show activation bursts composed of one or a few spikes that appear to have a very consistent pattern. Here, we place these findings in a broader context by comparing the MEPs, EMGs, and organization of the spinal motor neuron pools of flight muscles of Anna's hummingbird Calypte anna, zebra finches Taeniopygia guttata, and, for MEPs, several other species. The previously shown MEP pattern of the hummingbird pectoralis major is not shared with its closest taxonomic relative, the swift, and appears to be unique to hummingbirds. MEP arrangements in previously undocumented wing muscles show patterns that differ somewhat from other avian muscles. In the parallel-fibered strap muscles of the shoulder, MEP patterns appear to relate to muscle length, with the smallest muscles having fibers that span the entire muscle. MEP patterns in pennate distal wing muscles were the same regardless of size, with tightly clustered bands in the middle portion of the muscle, not evenly distributed bands over the muscle's entire length. Muscle activations were examined during slow forward flight in both species, during hovering in hummingbirds, and during slow ascents in zebra finches. The EMG bursts of a wing muscle, the pronator superficialis, were highly variable in peak number, size, and distribution across wingbeats for both species. In the pectoralis
Xu, Kai; Wang, Yueming; Zhang, Shaomin; Zhao, Ting; Wang, Yiwen; Chen, Weidong; Zheng, Xiaoxiang
Brain Machine Interfaces (BMI) aim at building a direct communication link between the neural system and external devices. The decoding of neuronal signals is one of the important steps in BMI systems. Existing decoding methods commonly fall into two categories, i.e., linear methods and nonlinear methods. This paper compares the performance between the two kinds of methods in the decoding of motor cortical activities of a monkey. Kalman filter (KF) is chosen as an example of linear methods, and General Regression Neural Network (GRNN) and Support Vector Regression (SVR) are two nonlinear approaches evaluated in our work. The experiments are conducted to reconstruct 2D trajectories in a center-out task. The correlation coefficient (CC) and the root mean square error (RMSE) are used to assess the performance. The experimental results show that GRNN and SVR achieve better performance than Kalman filter with average improvements of about 30% in CC and 40% in RMSE. This demonstrates that nonlinear models can better encode the relationship between the neuronal signals and response. In addition, GRNN and SVR are more effective than Kalman filter on noisy data.
Beck, Mikkel M.; Lind, Rune R.; Geertsen, Svend S.; Ritz, Christian; Lundbye-Jensen, Jesper; Wienecke, Jacob
Objective: An emerging field of research indicates that physical activity can benefit cognitive functions and academic achievements in children. However, less is known about how academic achievements can benefit from specific types of motor activities (e.g., fine and gross) integrated into learning activities. Thus, the aim of this study was to investigate whether fine or gross motor activity integrated into math lessons (i.e., motor-enrichment) could improve children's mathematical performance. Methods: A 6-week within school cluster-randomized intervention study investigated the effects of motor-enriched mathematical teaching in Danish preadolescent children (n = 165, age = 7.5 ± 0.02 years). Three groups were included: a control group (CON), which received non-motor enriched conventional mathematical teaching, a fine motor math group (FMM) and a gross motor math group (GMM), which received mathematical teaching enriched with fine and gross motor activity, respectively. The children were tested before (T0), immediately after (T1) and 8 weeks after the intervention (T2). A standardized mathematical test (50 tasks) was used to evaluate mathematical performance. Furthermore, it was investigated whether motor-enriched math was accompanied by different effects in low and normal math performers. Additionally, the study investigated the potential contribution of cognitive functions and motor skills on mathematical performance. Results: All groups improved their mathematical performance from T0 to T1. However, from T0 to T1, the improvement was significantly greater in GMM compared to FMM (1.87 ± 0.71 correct answers) (p = 0.02). At T2 no significant differences in mathematical performance were observed. A subgroup analysis revealed that normal math-performers benefitted from GMM compared to both CON 1.78 ± 0.73 correct answers (p = 0.04) and FMM 2.14 ± 0.72 correct answers (p = 0.008). These effects were not observed in low math-performers. The effects were partly
Beck, Mikkel M; Lind, Rune R; Geertsen, Svend S; Ritz, Christian; Lundbye-Jensen, Jesper; Wienecke, Jacob
Objective: An emerging field of research indicates that physical activity can benefit cognitive functions and academic achievements in children. However, less is known about how academic achievements can benefit from specific types of motor activities (e.g., fine and gross) integrated into learning activities. Thus, the aim of this study was to investigate whether fine or gross motor activity integrated into math lessons (i.e., motor-enrichment) could improve children's mathematical performance. Methods: A 6-week within school cluster-randomized intervention study investigated the effects of motor-enriched mathematical teaching in Danish preadolescent children (n = 165, age = 7.5 ± 0.02 years). Three groups were included: a control group (CON), which received non-motor enriched conventional mathematical teaching, a fine motor math group (FMM) and a gross motor math group (GMM), which received mathematical teaching enriched with fine and gross motor activity, respectively. The children were tested before (T0), immediately after (T1) and 8 weeks after the intervention (T2). A standardized mathematical test (50 tasks) was used to evaluate mathematical performance. Furthermore, it was investigated whether motor-enriched math was accompanied by different effects in low and normal math performers. Additionally, the study investigated the potential contribution of cognitive functions and motor skills on mathematical performance. Results: All groups improved their mathematical performance from T0 to T1. However, from T0 to T1, the improvement was significantly greater in GMM compared to FMM (1.87 ± 0.71 correct answers) (p = 0.02). At T2 no significant differences in mathematical performance were observed. A subgroup analysis revealed that normal math-performers benefitted from GMM compared to both CON 1.78 ± 0.73 correct answers (p = 0.04) and FMM 2.14 ± 0.72 correct answers (p = 0.008). These effects were not observed in low math-performers. The effects were partly
Ally, Shabeen; Larson, Adam G.; Barlan, Kari; Rice, Sarah E.
Intracellular transport is typically bidirectional, consisting of a series of back and forth movements. Kinesin-1 and cytoplasmic dynein require each other for bidirectional transport of intracellular cargo along microtubules; i.e., inhibition or depletion of kinesin-1 abolishes dynein-driven cargo transport and vice versa. Using Drosophila melanogaster S2 cells, we demonstrate that replacement of endogenous kinesin-1 or dynein with an unrelated, peroxisome-targeted motor of the same directionality activates peroxisome transport in the opposite direction. However, motility-deficient versions of motors, which retain the ability to bind microtubules and hydrolyze adenosine triphosphate, do not activate peroxisome motility. Thus, any pair of opposite-polarity motors, provided they move along microtubules, can activate one another. These results demonstrate that mechanical interactions between opposite-polarity motors are necessary and sufficient for bidirectional organelle transport in live cells. PMID:20038680
Gardini, Simona; Venneri, Annalena; McGeown, William Jonathan; Toraci, Cristian; Nocetti, Luca; Porro, Carlo Adolfo; Caffarra, Paolo
Motor behaviour is controlled by a large set of interacting neural structures, subserving the different components involved in hierarchical motor processes. Few studies have investigated the neural substrate of higher-order motor ideation, i.e. the mental operation of conceiving a movement. The aim of this functional magnetic resonance imaging study was to segregate the neural structures involved in motor ideation from those involved in movement choice and execution. An index finger movement paradigm was adopted, including three different conditions: performing a pre-specified movement, choosing and executing a movement and ideating a movement of choice. The tasks involved either the right or left hand, in separate runs. Neuroimaging results were obtained by comparing the different experimental conditions and computing conjunction maps of the right and left hands for each contrast. Pre-specified movement execution was supported by bilateral fronto-parietal motor regions, the cerebellum and putamen. Choosing and executing finger movement involved mainly left fronto-temporal areas and the anterior cingulate. Motor ideation activated almost exclusively left hemisphere regions, including the inferior, middle and superior frontal regions, middle temporal and middle occipital gyri. These findings show that motor ideation is controlled by a cortical network mainly involved in abstract thinking, cognitive and motor control, semantic and visual imagery processes.
Zhang, Xu; Li, Yun; Chen, Xiang; Li, Guanglin; Rymer, William Zev; Zhou, Ping
This study investigates the effect of involuntary motor activity of paretic-spastic muscles on classification of surface electromyography (EMG) signals. Two data collection sessions were designed for 8 stroke subjects to voluntarily perform 11 functional movements using their affected forearm and hand at a relatively slow and fast speed. For each stroke subject, the degree of involuntary motor activity present in voluntary surface EMG recordings was qualitatively described from such slow and fast experimental protocols. Myoelectric pattern recognition analysis was performed using different combinations of voluntary surface EMG data recorded from slow and fast sessions. Across all tested stroke subjects, our results revealed that when involuntary surface EMG was absent or present in both training and testing datasets, high accuracies (> 96%, > 98%, respectively, averaged over all the subjects) can be achieved in classification of different movements using surface EMG signals from paretic muscles. When involuntary surface EMG was solely involved in either training or testing datasets, the classification accuracies were dramatically reduced (< 89%, < 85%, respectively). However, if both training and testing datasets contained EMG signals with presence and absence of involuntary EMG interference, high accuracies were still achieved (> 97%). The findings of this study can be used to guide appropriate design and implementation of myoelectric pattern recognition based systems or devices toward promoting robot-aided therapy for stroke rehabilitation. PMID:23860192
Zhang, Xu; Li, Yun; Chen, Xiang; Li, Guanglin; Zev Rymer, William; Zhou, Ping
Objective. This study investigates the effect of the involuntary motor activity of paretic-spastic muscles on the classification of surface electromyography (EMG) signals. Approach. Two data collection sessions were designed for 8 stroke subjects to voluntarily perform 11 functional movements using their affected forearm and hand at relatively slow and fast speeds. For each stroke subject, the degree of involuntary motor activity present in the voluntary surface EMG recordings was qualitatively described from such slow and fast experimental protocols. Myoelectric pattern recognition analysis was performed using different combinations of voluntary surface EMG data recorded from the slow and fast sessions. Main results. Across all tested stroke subjects, our results revealed that when involuntary surface EMG is absent or present in both the training and testing datasets, high accuracies (>96%, >98%, respectively, averaged over all the subjects) can be achieved in the classification of different movements using surface EMG signals from paretic muscles. When involuntary surface EMG was solely involved in either the training or testing datasets, the classification accuracies were dramatically reduced (<89%, <85%, respectively). However, if both the training and testing datasets contained EMG signals with the presence and absence of involuntary EMG interference, high accuracies were still achieved (>97%). Significance. The findings of this study can be used to guide the appropriate design and implementation of myoelectric pattern recognition based systems or devices toward promoting robot-aided therapy for stroke rehabilitation.
Llinas, Paola; Isabet, Tatiana; Song, Lin; Ropars, Virginie; Zong, Bin; Benisty, Hannah; Sirigu, Serena; Morris, Carl; Kikuti, Carlos; Safer, Dan; Sweeney, H. Lee; Houdusse, Anne
SUMMARY Fundamental to cellular processes are directional movements driven by molecular motors. A common theme for these and other molecular machines driven by ATP is that controlled release of hydrolysis products is essential to use the chemical energy efficiently. Mechanochemical transduction by myosin motors on actin is coupled to unknown structural changes that result in the sequential release of inorganic phosphate (Pi) and MgADP. We present here a myosin structure possessing an actin-binding interface and a tunnel (back door) that creates an escape route for Pi with a minimal rotation of the myosin lever arm that drives movements. We propose that this state represents the beginning of the powerstroke on actin, and that Pi translocation from the nucleotide pocket triggered by actin binding initiates myosin force generation. This elucidates how actin initiates force generation and movement, and may represent a strategy common to many molecular machines. PMID:25936506
Morillon, Benjamin; Hackett, Troy A; Kajikawa, Yoshinao; Schroeder, Charles E
Neuronal oscillations present potential physiological substrates for brain operations that require temporal prediction. We review this idea in the context of auditory perception. Using speech as an exemplar, we illustrate how hierarchically organized oscillations can be used to parse and encode complex input streams. We then consider the motor system as a major source of rhythms (temporal priors) in auditory processing, that act in concert with attention to sharpen sensory representations and link them across areas. We discuss the circuits that could mediate this audio-motor interaction, notably the potential role of the somatosensory system. Finally, we reposition temporal predictions in the context of internal models, discussing how they interact with feature-based or spatial predictions. We argue that complementary predictions interact synergistically according to the organizational principles of each sensory system, forming multidimensional filters crucial to perception.
Llinas, Paola; Isabet, Tatiana; Song, Lin; Ropars, Virginie; Zong, Bin; Benisty, Hannah; Sirigu, Serena; Morris, Carl; Kikuti, Carlos; Safer, Dan; Sweeney, H Lee; Houdusse, Anne
Fundamental to cellular processes are directional movements driven by molecular motors. A common theme for these and other molecular machines driven by ATP is that controlled release of hydrolysis products is essential for using the chemical energy efficiently. Mechanochemical transduction by myosin motors on actin is coupled to unknown structural changes that result in the sequential release of inorganic phosphate (Pi) and MgADP. We present here a myosin structure possessing an actin-binding interface and a tunnel (back door) that creates an escape route for Pi with a minimal rotation of the myosin lever arm that drives movements. We propose that this state represents the beginning of the powerstroke on actin and that Pi translocation from the nucleotide pocket triggered by actin binding initiates myosin force generation. This elucidates how actin initiates force generation and movement and may represent a strategy common to many molecular machines.
Lago, Angel; Fernandez-del-Olmo, Miguel
There are human cortical areas that fire both when a person executes an action and when he observes someone performing a similar action. The observer activates a motor program that resembles the observed action. However, it is not known whether the motor program activated via action observation is muscle specific. In this study, using simple pulse transcranial magnetic stimulation (TMS) applied over the primary motor cortex (M1), we investigated whether the Mirror System activates a muscle specific motor program, or codes the observed action in terms of its goal. The results showed that when subjects observed a static effector in front of an object, cortical excitability was enhanced even in muscles not involved in the observed movement, but that are able to achieve the goal of the action. When there was an effector-object interaction the motor program activated via action observation is muscle specific. These results suggest that when subjects observe an object related action there is an activation of a motor program based on the observed action goal, that is transformed into a muscle specific program when the subject shows an effector-object interaction.
Kantomaa, Marko T.; Stamatakis, Emmanuel; Kankaanpää, Anna; Kaakinen, Marika; Rodriguez, Alina; Taanila, Anja; Ahonen, Timo; Järvelin, Marjo-Riitta; Tammelin, Tuija
The global epidemic of obesity and physical inactivity may have detrimental implications for young people’s cognitive function and academic achievement. This prospective study investigated whether childhood motor function predicts later academic achievement via physical activity, fitness, and obesity. The study sample included 8,061 children from the Northern Finland Birth Cohort 1986, which contains data about parent-reported motor function at age 8 y and self-reported physical activity, predicted cardiorespiratory fitness (cycle ergometer test), obesity (body weight and height), and academic achievement (grades) at age 16 y. Structural equation models with unstandardized (B) and standardized (β) coefficients were used to test whether, and to what extent, physical activity, cardiorespiratory fitness, and obesity at age 16 mediated the association between childhood motor function and adolescents’ academic achievement. Physical activity was associated with a higher grade-point average, and obesity was associated with a lower grade-point average in adolescence. Furthermore, compromised motor function in childhood had a negative indirect effect on adolescents’ academic achievement via physical inactivity (B = –0.023, 95% confidence interval = –0.031, –0.015) and obesity (B = –0.025, 95% confidence interval = –0.039, –0.011), but not via cardiorespiratory fitness. These results suggest that physical activity and obesity may mediate the association between childhood motor function and adolescents’ academic achievement. Compromised motor function in childhood may represent an important factor driving the effects of obesity and physical inactivity on academic underachievement. PMID:23277558
Papegaaij, Selma; Taube, Wolfgang; van Keeken, Helco G; Otten, Egbert; Baudry, Stéphane; Hortobágyi, Tibor
When humans voluntarily activate a muscle, intracortical inhibition decreases. Such a decrease also occurs in the presence of a postural challenge and more so with increasing age. Here, we examined age-related changes in motor cortical activity during postural and non-postural contractions with varying levels of postural challenge. Fourteen young (age 22) and twelve old adults (age 70) performed three conditions: (1) voluntary contraction of the soleus muscle in sitting and (2) leaning forward while standing with and (3) without being supported. Subthreshold transcranial magnetic stimulation was applied to the soleus motor area suppressing ongoing EMG, as an index of motor cortical activity. The area of EMG suppression was ~60% smaller (p<0.05) in unsupported vs. supported leaning and sitting, with no difference between these latter two conditions (p>0.05). Even though in absolute terms young compared with old adults leaned farther (p=0.018), there was no age effect or an age by condition interaction in EMG suppression. Leaning closer to the maximum without support correlated with less EMG suppression (rho=-0.44, p=0.034). We conclude that the critical factor in modulating motor cortical activity was postural challenge and not contraction aim or posture. Age did not affect the motor control strategy as quantified by the modulation of motor cortical activity, but the modulation appeared at a lower task difficulty with increasing age.
Kantomaa, Marko T; Stamatakis, Emmanuel; Kankaanpää, Anna; Kaakinen, Marika; Rodriguez, Alina; Taanila, Anja; Ahonen, Timo; Järvelin, Marjo-Riitta; Tammelin, Tuija
The global epidemic of obesity and physical inactivity may have detrimental implications for young people's cognitive function and academic achievement. This prospective study investigated whether childhood motor function predicts later academic achievement via physical activity, fitness, and obesity. The study sample included 8,061 children from the Northern Finland Birth Cohort 1986, which contains data about parent-reported motor function at age 8 y and self-reported physical activity, predicted cardiorespiratory fitness (cycle ergometer test), obesity (body weight and height), and academic achievement (grades) at age 16 y. Structural equation models with unstandardized (B) and standardized (β) coefficients were used to test whether, and to what extent, physical activity, cardiorespiratory fitness, and obesity at age 16 mediated the association between childhood motor function and adolescents' academic achievement. Physical activity was associated with a higher grade-point average, and obesity was associated with a lower grade-point average in adolescence. Furthermore, compromised motor function in childhood had a negative indirect effect on adolescents' academic achievement via physical inactivity (B = -0.023, 95% confidence interval = -0.031, -0.015) and obesity (B = -0.025, 95% confidence interval = -0.039, -0.011), but not via cardiorespiratory fitness. These results suggest that physical activity and obesity may mediate the association between childhood motor function and adolescents' academic achievement. Compromised motor function in childhood may represent an important factor driving the effects of obesity and physical inactivity on academic underachievement.
Kas, M J H; de Mooij-van Malsen, J G; de Krom, M; van Gassen, K L I; van Lith, H A; Olivier, B; Oppelaar, H; Hendriks, J; de Wit, M; Groot Koerkamp, M J A; Holstege, F C P; van Oost, B A; de Graan, P N E
The generation of motor activity levels is under tight neural control to execute essential behaviors, such as movement toward food or for social interaction. To identify novel neurobiological mechanisms underlying motor activity levels, we studied a panel of chromosome substitution (CS) strains derived from mice with high (C57BL/6J strain) or low motor activity levels (A/J strain) using automated home cage behavioral registration. In this study, we genetically mapped the expression of baseline motor activity levels (horizontal distance moved) to mouse chromosome 1. Further genetic mapping of this trait revealed an 8.3-Mb quantitative trait locus (QTL) interval. This locus is distinct from the QTL interval for open-field anxiety-related motor behavior on this chromosome. By data mining, an existing phenotypic and genotypic data set of 2445 genetically heterogeneous mice (http://gscan.well.ox.ac.uk/), we confirmed linkage to the peak marker at 79 970 253 bp and refined the QTL to a 312-kb interval containing a single gene (A830043J08Rik). Sequence analysis showed a nucleotide deletion in the 3' untranslated region of the Riken gene. Genome-wide microarray gene expression profiling in brains of discordant F(2) individuals from CS strain 1 showed a significant upregulation of Epha4 in low-active F(2) individuals. Inclusion of a genetic marker for Epha4 confirmed that this gene is located outside of the QTL interval. Both Epha4 and A830043J08Rik are expressed in brain motor circuits, and similar to Epha4 mutants, we found linkage between reduced motor neurons number and A/J chromosome 1. Our findings provide a novel QTL and a potential downstream target underlying motor circuitry development and the expression of physical activity levels.
effects . Contributed talks by Francisco Raymo and Dongwhan Lee were followed by the second invited talk by Miguel Garcia-Garibay from UCLA...to 100 scientists in the audience for almost all talks. The large fraction of invited talks resulted in a consistently high quality of presentations...and engineers, and the large number of parallel symposia draws in attendees who are more peripherally interested in molecular motors. The main
Williams, Harriet G.; Pfeiffer, Karin A.; Dowda, Marsha; Jeter, Chevy; Jones, Shaverra; Pate, Russell R.
The purpose of this study was to develop a valid and reliable tool for use in assessing motor skills in preschool children in field-based settings. The development of the Children's Activity and Movement in Preschool Study Motor Skills Protocol included evidence of its reliability and validity for use in field-based environments as part of large…
Silva, Kalinga Pavan; Chellamuthu, Prithiviraj; Boedicker, James Q
Diverse microbial communities coordinate group behaviors through signal exchange, such as the exchange of acyl-homoserine lactones (AHLs) by Gram-negative bacteria. Cellular communication is prone to interference by neighboring microbes. One mechanism of interference is signal destruction through the production of an enzyme that cleaves the signaling molecule. Here we examine the ability of one such interference enzyme, AiiA, to modulate signal propagation in a spatially distributed system of bacteria. We have developed an experimental assay to measure signal transduction and implement a theoretical model of signaling dynamics to predict how the system responds to interference. We show that titration of an interfering strain into a signaling network tunes the spatial range of activation over the centimeter length scale, quantifying the robustness of the signaling network to signal destruction and demonstrating the ability to program systems-level responses of spatially heterogeneous cellular networks.
Mishra, Abhinava K; Sachan, Nalani; Mutsuddi, Mousumi; Mukherjee, Ashim
Notch signaling pathway represents a principal cellular communication system that plays a pivotal role during development of metazoans. Drosophila misshapen (msn) encodes a protein kinase, which is related to the budding yeast Ste20p (sterile 20 protein) kinase. In a genetic screen, using candidate gene approach to identify novel kinases involved in Notch signaling, we identified msn as a novel regulator of Notch signaling. Data presented here suggest that overexpression of kinase active form of Msn exhibits phenotypes similar to Notch loss-of-function condition and msn genetically interacts with components of Notch signaling pathway. Kinase active form of Msn associates with Notch receptor and regulate its signaling activity. We further show that kinase active Misshapen leads to accumulation of membrane-tethered form of Notch. Moreover, activated Msn also depletes Armadillo and DE-Cadherin from adherens junctions. Thus, this study provides a yet unknown mode of regulation of Notch signaling by Misshapen.
De Carli, Fabrizio; Proserpio, Paola; Morrone, Elisa; Sartori, Ivana; Ferrara, Michele; Gibbs, Steve Alex; De Gennaro, Luigi; Lo Russo, Giorgio
When dreaming during rapid eye movement (REM) sleep, we can perform complex motor behaviors while remaining motionless. How the motor cortex behaves during this state remains unknown. Here, using intracerebral electrodes sampling the human motor cortex in pharmacoresistant epileptic patients, we report a pattern of electroencephalographic activation during REM sleep similar to that observed during the performance of a voluntary movement during wakefulness. This pattern is present during phasic REM sleep but not during tonic REM sleep, the latter resembling relaxed wakefulness. This finding may help clarify certain phenomenological aspects observed in REM sleep behavior disorder. Ann Neurol 2016;79:326–330 PMID:26575212
Brusnichkina, R I
Complex motor acts of pilots during their professional work were investigated with control information presented in a different manner. Two experimental series were run: in a real flight and in a simulator. Parameters of muscle bioelectric activity, control movements and performance efficiency were used. Differences in the formation of motor acts were shown to depend on the scope and quality of the information presented. During required transfer from one mode to another the structure of working movements and performance efficiency obeyed at large changes in the information necessary for piloting. This was accompanied by an alteration in the developed stereotype of actions, including motor acts.
Wandschneider, Britta; Centeno, Maria; Vollmar, Christian; Symms, Mark; Thompson, Pamela J.; Duncan, John S.
Juvenile myoclonic epilepsy is a heritable idiopathic generalized epilepsy syndrome, characterized by myoclonic jerks and frequently triggered by cognitive effort. Impairment of frontal lobe cognitive functions has been reported in patients with juvenile myoclonic epilepsy and their unaffected siblings. In a recent functional magnetic resonance imaging study we reported abnormal co-activation of the motor cortex and increased functional connectivity between the motor system and prefrontal cognitive networks during a working memory paradigm, providing an underlying mechanism for cognitively triggered jerks. In this study, we used the same task in 15 unaffected siblings (10 female; age range 18–65 years, median 40) of 11 of those patients with juvenile myoclonic epilepsy (six female; age range 22–54 years, median 35) and compared functional magnetic resonance imaging activations with 20 age- and gender-matched healthy control subjects (12 female; age range 23–46 years, median 30.5). Unaffected siblings showed abnormal primary motor cortex and supplementary motor area co-activation with increasing cognitive load, as well as increased task-related functional connectivity between motor and prefrontal cognitive networks, with a similar pattern to patients (P < 0.001 uncorrected; 20-voxel threshold extent). This finding in unaffected siblings suggests that altered motor system activation and functional connectivity is not medication- or seizure-related, but represents a potential underlying mechanism for impairment of frontal lobe functions in both patients and siblings, and so constitutes an endophenotype of juvenile myoclonic epilepsy. PMID:25001494
Lam, A. T.; VanDelinder, V.; Kabir, A. M. R.; ...
Molecular motor-driven self-assembly has been an active area of soft matter research for the past decade. Because molecular motors transform chemical energy into mechanical work, systems which employ molecular motors to drive self-assembly processes are able to overcome kinetic and thermodynamic limits on assembly time, size, complexity, and structure. Here, we review the progress in elucidating and demonstrating the rules and capabilities of motor-driven active self-assembly. Lastly, we focus on the types of structures created and the degree of control realized over these structures, and discuss the next steps necessary to achieve the full potential of this assembly mode whichmore » complements robotic manipulation and passive self-assembly.« less
Tang, Qing; Pollard, Luther W; Lord, Matthew
Fission yeast myosin-II (Myo2p) represents the critical actin-based motor protein that drives actomyosin ring assembly and constriction during cytokinesis. We detail three different methods to measure Myo2p motor function. Actin-activated ATPases provide a readout of actomyosin ATPase motor activity in a bulk assay; actin filament motility assays reveal the speed and efficiency of myosin-driven actin filament gliding (when motors are anchored); myosin-bead motility assays reveal the speed and efficiency of myosin ensembles traveling along actin filaments (when actin is anchored). Collectively, these methods allow us to combine the standard in vivo approaches common to fission yeast with in vitro biochemical methods to learn more about the mechanistic action of myosin-II during cytokinesis.
Lam, A. T.; VanDelinder, V.; Hess, H.; Bachand, G. D.
Molecular motor-driven self-assembly has been an active area of soft matter research for the past decade. Because molecular motors transform chemical energy into mechanical work, systems which employ molecular motors to drive self-assembly processes are able to overcome kinetic and thermodynamic limits on assembly time, size, complexity, and structure. Here, we review the progress in elucidating and demonstrating the rules and capabilities of motor-driven active self-assembly. Lastly, we focus on the types of structures created and the degree of control realized over these structures, and discuss the next steps necessary to achieve the full potential of this assembly mode which complements robotic manipulation and passive self-assembly.
Erwin, Heather E.; Woods, Amelia Mays; Woods, Martha K.; Castelli, Darla M.
The purpose of this study was to examine levels of physical activity engagement, motor competence, and physical fitness as related to child access to physical activity facilities in the home and school environments. The present investigation attempts to further efforts to examine the relationship between physical activity levels and access.…
Texas Child Care, 2003
Highlights the importance of activities to build gross motor skills and provides hints for encouraging such activities. Specific areas of activities presented are: (1) running and jumping; (2) music games; (3) action games; (4) races; (5) bed sheets or parachutes; (6) hula hoops; (7) balls; (8) batting; (9) balance; and (10) creative movement. (SD)
Lee, Joonyeol; Joshua, Mati; Medina, Javier F; Lisberger, Stephen G
Analysis of the neural code for sensory-motor latency in smooth pursuit eye movements reveals general principles of neural variation and the specific origin of motor latency. The trial-by-trial variation in neural latency in MT comprises a shared component expressed as neuron-neuron latency correlations and an independent component that is local to each neuron. The independent component arises heavily from fluctuations in the underlying probability of spiking, with an unexpectedly small contribution from the stochastic nature of spiking itself. The shared component causes the latency of single-neuron responses in MT to be weakly predictive of the behavioral latency of pursuit. Neural latency deeper in the motor system is more strongly predictive of behavioral latency. A model reproduces both the variance of behavioral latency and the neuron-behavior latency correlations in MT if it includes realistic neural latency variation, neuron-neuron latency correlations in MT, and noisy gain control downstream of MT.
Li, Hongfei; Chen, Ji-Hong; Yang, Zixian; Huang, Min; Yu, Yuanjie; Tan, Shiyun; Luo, Hesheng; Huizinga, Jan D
Background/Aims Neurotensin is a gut-brain peptide with both inhibitory and excitatory actions on the colonic musculature; our objective was to understand the implications of this for motor patterns occurring in the intact colon of the rat. Methods The effects of neurotensin with concentrations ranging from 0.1–100 nM were studied in the intact rat colon in vitro, by investigating spatio-temporal maps created from video recordings of colonic motility before and after neurotensin. Results Low concentration of neurotensin (0.1–1 nM) inhibited propagating long distance contractions and rhythmic propagating motor complexes; in its place a slow propagating rhythmic segmental motor pattern developed. The neurotensin receptor 1 antagonist SR-48692 prevented the development of the segmental motor pattern. Higher concentrations of neurotensin (10 nM and 100 nM) were capable of restoring long distance contraction activity and inhibiting the segmental activity. The slow propagating segmental contraction showed a rhythmic contraction—relaxation cycle at the slow wave frequency originating from the interstitial cells of Cajal associated with the myenteric plexus pacemaker. High concentrations given without prior additions of low concentrations did not evoke the segmental motor pattern. These actions occurred when neurotensin was given in the bath solution or intraluminally. The segmental motor pattern evoked by neurotensin was inhibited by the neural conduction blocker lidocaine. Conclusions Neurotensin (0.1–1 nM) inhibits the dominant propulsive motor patterns of the colon and a distinct motor pattern of rhythmic slow propagating segmental contractions develops. This motor pattern has the hallmarks of haustral boundary contractions. PMID:26882114
Kazennikov, O V; Lipshits, M I
Object fell into the cup that sitting subject held between thumb and index fingers. Transcranial magnetic stimulation (TMS) of the primary motor cortex was performed early before and during anticipatory grip force increasing. Comparison of current EMG activity of adductor pollicis brevis and first dorsal interosseous muscles and responses of these muscles on TMS showed that responses were increased before the raising of muscle activity. From the other side only slight augmentation of responses was observed during subsequent strong muscle activation. It is assumed that the increasing of the TMS responses that occurred before the initiation of muscle activity reflects the enhancement ofthe motor cortex excitability associated to specific processes related to the motor cortex participation in programming of the muscles activities.
Lee, Kyung H.; Kim, Un J.; Park, Se W.; Park, Yong G.; Lee, Bae H.
Spinal cord injury (SCI) disrupts neuronal networks of ascending and descending tracts at the site of injury, leading to a loss of motor function. Restoration and new circuit formation are important components of the recovery process, which involves collateral sprouting of injured and uninjured fibers. The present study was conducted to determine cortical responses to antidromic stimulation of the corticospinal tracts, to compare changes in the reorganization of neural pathways within normal and spinal cord-injured rats, and to elucidate differences in spatiotemporal activity patterns of the natural progression and reorganization of neural pathways in normal and SCI animals using optical imaging. Optical signals were recorded from the motor cortex in response to electrical stimulation of the ventral horn of the L1 spinal cord. Motor evoked potentials (MEPs) were evaluated to demonstrate endogenous recovery of physiological functions after SCI. A significantly shorter N1 peak latency and broader activation in the MEP optical recordings were observed at 4 weeks after SCI, compared to 1 week after SCI. Spatiotemporal patterns in the cerebral cortex differed depending on functional recovery. In the present study, optical imaging was found to be useful in revealing functional changes and may reflect conditions of reorganization and/or changes in surviving neurons after SCI.
Shaylor, Lara A; Hwang, Sung Jin; Sanders, Kenton M; Ward, Sean M
Inhibitory motor neurons regulate several gastric motility patterns including receptive relaxation, gastric peristaltic motor patterns, and pyloric sphincter opening. Nitric oxide (NO) and purines have been identified as likely candidates that mediate inhibitory neural responses. However, the contribution from each neurotransmitter has received little attention in the distal stomach. The aims of this study were to identify the roles played by NO and purines in inhibitory motor responses in the antrums of mice and monkeys. By using wild-type mice and mutants with genetically deleted neural nitric oxide synthase (Nos1(-/-)) and P2Y1 receptors (P2ry1(-/-)) we examined the roles of NO and purines in postjunctional inhibitory responses in the distal stomach and compared these responses to those in primate stomach. Activation of inhibitory motor nerves using electrical field stimulation (EFS) produced frequency-dependent inhibitory junction potentials (IJPs) that produced muscle relaxations in both species. Stimulation of inhibitory nerves during slow waves terminated pacemaker events and associated contractions. In Nos1(-/-) mice IJPs and relaxations persisted whereas in P2ry1(-/-) mice IJPs were absent but relaxations persisted. In the gastric antrum of the non-human primate model Macaca fascicularis, similar NO and purine neural components contributed to inhibition of gastric motor activity. These data support a role of convergent inhibitory neural responses in the regulation of gastric motor activity across diverse species.
Grandjean, Bernard; Maier, Marc A
Muscle spindle discharge during active movement is a function of mechanical and neural parameters. Muscle length changes (and their derivatives) represent its primary mechanical, fusimotor drive its neural component. However, neither the action nor the function of fusimotor and in particular of γ-drive, have been clearly established, since γ-motor activity during voluntary, non-locomotor movements remains largely unknown. Here, using a computational approach, we explored whether γ-drive emerges in an artificial neural network model of the corticospinal system linked to a biomechanical antagonist wrist simulator. The wrist simulator included length-sensitive and γ-drive-dependent type Ia and type II muscle spindle activity. Network activity and connectivity were derived by a gradient descent algorithm to generate reciprocal, known target α-motor unit activity during wrist flexion-extension (F/E) movements. Two tasks were simulated: an alternating F/E task and a slow F/E tracking task. Emergence of γ-motor activity in the alternating F/E network was a function of α-motor unit drive: if muscle afferent (together with supraspinal) input was required for driving α-motor units, then γ-drive emerged in the form of α-γ coactivation, as predicted by empirical studies. In the slow F/E tracking network, γ-drive emerged in the form of α-γ dissociation and provided critical, bidirectional muscle afferent activity to the cortical network, containing known bidirectional target units. The model thus demonstrates the complementary aspects of spindle output and hence γ-drive: i) muscle spindle activity as a driving force of α-motor unit activity, and ii) afferent activity providing continuous sensory information, both of which crucially depend on γ-drive.
Docx, Lise; Emsell, Louise; Van Hecke, Wim; De Bondt, Timo; Parizel, Paul M; Sabbe, Bernard; Morrens, Manuel
Avolition is a core feature of schizophrenia and may arise from altered brain connectivity. Here we used diffusion kurtosis imaging (DKI) to investigate the association between white matter (WM) microstructure and volitional motor activity. Multi-shell diffusion MRI and 24-h actigraphy data were obtained from 20 right-handed patients with schizophrenia and 16 right-handed age and gender matched healthy controls. We examined correlations between fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), and motor activity level, as well as group differences in these measures. In the patient group, increasing motor activity level was positively correlated with MK in the inferior, medial and superior longitudinal fasciculus, the corpus callosum, the posterior fronto-occipital fasciculus and the posterior cingulum. This association was not found in control subjects or in DTI measures. These results show that a lack of volitional motor activity in schizophrenia is associated with potentially altered WM microstructure in posterior brain regions associated with cognitive function and motivation. This could reflect both illness related dysconnectivity which through altered cognition, manifests as reduced volitional motor activity, and/or the effects of reduced physical activity on brain WM.
Conjeevaram, H S; Mullen, K D; May, E J; McCullough, A J
Alterations in behavior are frequently described in rats subjected to portacaval shunt. Previous work has reported reduced spontaneous motor activity in various settings (nighttime, red light, decreased illumination) in this animal model. We investigated this phenomenon in rats of both genders subjected to portacaval shunt to determine whether our previously observed divergent growth patterns (males reduced, females unchanged) had any impact on the alterations in spontaneous motor activity in this model. Dietary intake, growth, motor activity and serum ammonia and amino acid concentrations were measured, in addition to final liver and spleen weights, in each animal after 3 to 4 wk of observation. Our results reconfirm the differential impact of portacaval shunt on growth in male (35% reduction p < 0.01) but not female rats (5% reduction, NS) compared with their respective-gender sham-operated controls. In addition, spontaneous motor activity was significantly reduced in male (congruent to 50%, p = 0.01) but not female rats subjected to portacaval shunt. The reduction of activity in male rats subjected to portacaval shunt did not correlate with any of the measured biochemical data or calculated nutritional/growth parameters. Thus we observed gender-dependent reduction in spontaneous motor activity after portacaval shunt in the rat. The mechanism for this phenomenon is unknown, but it is easily investigated with this reproducible model.
Case, Laura K; Pineda, Jaime; Ramachandran, Vilayanur S
Motor imagery and perception- considered generally as forms of motor simulation- share overlapping neural representations with motor production. While much research has focused on the extent of this “common coding,” less attention has been paid to how these overlapping representations interact. How do imagined, observed, or produced actions influence one another, and how do we maintain control over our perception and behavior? In the first part of this review we describe interactions between motor production and motor simulation, and explore apparent regulatory mechanisms that balance these processes. Next, we consider the somatosensory system. Numerous studies now support a “sensory mirror system” comprised of neural representations activated by either afferent sensation or vicarious sensation. In the second part of this review we summarize evidence for shared representations of sensation and sensory simulation (including imagery and observed sensation), and suggest that similar interactions and regulation of simulation occur in the somatosensory domain as in the motor domain. We suggest that both motor and somatosensory simulations are flexibly regulated to support simulations congruent with our sensorimotor experience and goals and suppress or separate the influence of those that are not. These regulatory mechanisms are frequently revealed by cases of brain injury but can also be employed to facilitate sensorimotor rehabilitation. PMID:25863237
Tortella, Patrizia; Haga, Monika; Loras, Håvard
This study examined the effects and specificity of structured and unstructured activities played at the playground Primo Sport 0246 in Northern Italy on motor skill competence in five years old children. The playground was specifically designed to promote gross motor skills in preschool children; in this study 71 children from local kindergartens came to the park once a week for ten consecutive weeks and were exposed to 30 minutes of free play and 30 minutes of structured activities. Before and after the ten visits, each child completed nine tests to assess levels of motor skills, three for fine-motor skills and six for gross-motor skills. As control, motor skills were also assessed on 39 children from different kindergartens who did not come to the park. The results show that the experimental group who practiced gross-motor activities in the playground for 1 hour a week for 10 weeks improved significantly in 4 out of the 6 gross motor tasks and in none of the fine motor tasks. The data indicate that limited transfer occurred between tasks referring to different domains of motor competences while suggesting cross feeding for improvement of gross-motor skills between different exercises when domains related to physical fitness and strength of specific muscle groups are involved. These results are relevant to the issue of condition(s) appropriate for maintaining and developing motor skills in this age group as well as for the planning, organization and implementation of play and physical activities in kindergartens. PMID:27462985
Tschentscher, Nadja; Hauk, Olaf; Fischer, Martin H.; Pulvermüller, Friedemann
The embodied cognition framework suggests that neural systems for perception and action are engaged during higher cognitive processes. In an event-related fMRI study, we tested this claim for the abstract domain of numerical symbol processing: is the human cortical motor system part of the representation of numbers, and is organization of numerical knowledge influenced by individual finger counting habits? Developmental studies suggest a link between numerals and finger counting habits due to the acquisition of numerical skills through finger counting in childhood. In the present study, digits 1 to 9 and the corresponding number words were presented visually to adults with different finger counting habits, i.e. left- and right-starters who reported that they usually start counting small numbers with their left and right hand, respectively. Despite the absence of overt hand movements, the hemisphere contralateral to the hand used for counting small numbers was activated when small numbers were presented. The correspondence between finger counting habits and hemispheric motor activation is consistent with an intrinsic functional link between finger counting and number processing. PMID:22133748
Maciejewski, Marcin; Surtel, Wojciech; Dzida, Grzegorz
ECG signal parameters are commonly used indicators of human health condition. In most cases the patient should remain stationary during the examination to decrease the influence of muscle artifacts. During physical activity, the noise level increases significantly. The ECG signals were acquired during controlled physical activity on a stationary bicycle and during rest. Afterwards, the signals were processed using a method based on Pan-Tompkins algorithms to estimate their parameters and to test the method.
Smyk, Magdalena K; Coenen, Anton M L; Lewandowski, Marian H; van Luijtelaar, Gilles
The rhythms of spontaneously occurring seizures (spike-wave discharges, SWD) and motor activity, as well as the relationship between SWD and sleep-wake states were investigated in the WAG/Rij rat model of absence epilepsy. In order to establish whether SWD are controlled by external (Zeitgebers) or by endogenous factors such as circadian influences or the state of vigilance, the study was performed in entrained and constant dim light conditions. EEG and motor activity were recorded in the 12:12 light-dark cycle and in constant dim light conditions. Circadian rhythmicity was found both for motor activity and the occurrence of SWD in conditions of entrainment. In constant dim light conditions also circadian rhythms emerged, however, the change in circadian parameters was opposite for the rhythm of SWD and motor activity. SWD were preceded mostly by passive wakefulness and by slow-wave sleep in both experimental conditions. It can be concluded that the rhythm of SWD seems to be generated and controlled by an endogenous mechanism distinct from that which controls the rhythm of motor activity. The relationship between SWD and sleep-wake states preceding their occurrences appeared to be unchanged, suggesting that the mechanism of generation of SWD is independent of the circadian timing system.
Aaltonen, Sari; Latvala, Antti; Rose, Richard J.; Pulkkinen, Lea; Kujala, Urho M.; Kaprio, Jaakko; Silventoinen, Karri
Introduction Previous longitudinal research suggests that motor proficiency in early life predicts physical activity in adulthood. Familial effects including genetic and environmental factors could explain the association, but no long-term follow-up studies have taken into account potential confounding by genetic and social family background. The present twin study investigated whether childhood motor skill development is associated with leisure-time physical activity levels in adulthood independent of family background. Methods Altogether, 1 550 twin pairs from the FinnTwin12 study and 1 752 twin pairs from the FinnTwin16 study were included in the analysis. Childhood motor development was assessed by the parents’ report of whether one of the co-twins had been ahead of the other in different indicators of motor skill development in childhood. Leisure-time physical activity (MET hours/day) was self-reported by the twins in young adulthood and adulthood. Statistical analyses included conditional and ordinary linear regression models within twin pairs. Results Using all activity-discordant twin pairs, the within-pair difference in a sum score of motor development in childhood predicted the within-pair difference in the leisure-time physical activity level in young adulthood (p<0.001). Within specific motor development indicators, learning to stand unaided earlier in infancy predicted higher leisure-time MET values in young adulthood statistically significantly in both samples (FinnTwin12 p=0.02, FinnTwin16 p=0.001) and also in the pooled dataset of the FinnTwin12 and FinnTwin16 studies (p<0.001). Having been more agile than the co-twin as a child predicted higher leisure-time MET values up to adulthood (p=0.03). Conclusions More advanced childhood motor development is associated with higher leisure-time MET values in young adulthood at least partly independent of family background, in both men and women. PMID:26378945
Villiger, Michael; Estévez, Natalia; Hepp-Reymond, Marie-Claude; Kiper, Daniel; Kollias, Spyros S; Eng, Kynan; Hotz-Boendermaker, Sabina
The combination of first-person observation and motor imagery, i.e. first-person observation of limbs with online motor imagination, is commonly used in interactive 3D computer gaming and in some movie scenes. These scenarios are designed to induce a cognitive process in which a subject imagines himself/herself acting as the agent in the displayed movement situation. Despite the ubiquity of this type of interaction and its therapeutic potential, its relationship to passive observation and imitation during observation has not been directly studied using an interactive paradigm. In the present study we show activation resulting from observation, coupled with online imagination and with online imitation of a goal-directed lower limb movement using functional MRI (fMRI) in a mixed block/event-related design. Healthy volunteers viewed a video (first-person perspective) of a foot kicking a ball. They were instructed to observe-only the action (O), observe and simultaneously imagine performing the action (O-MI), or imitate the action (O-IMIT). We found that when O-MI was compared to O, activation was enhanced in the ventralpremotor cortex bilaterally, left inferior parietal lobule and left insula. The O-MI and O-IMIT conditions shared many activation foci in motor relevant areas as confirmed by conjunction analysis. These results show that (i) combining observation with motor imagery (O-MI) enhances activation compared to observation-only (O) in the relevant foot motor network and in regions responsible for attention, for control of goal-directed movements and for the awareness of causing an action, and (ii) it is possible to extensively activate the motor execution network using O-MI, even in the absence of overt movement. Our results may have implications for the development of novel virtual reality interactions for neurorehabilitation interventions and other applications involving training of motor tasks.
Matsukawa, Kanji; Ishii, Kei; Kadowaki, Akito; Ishida, Tomoko; Idesako, Mitsuhiro; Liang, Nan
Our laboratory has demonstrated that the cardiomotor component of aortic baroreflex is temporarily inhibited at the onset of spontaneous motor activity in decerebrate cats, without altering carotid sinus baroreflex. A reason for this dissociation may be attributed to a difference in the responses between aortic nerve activity (AoNA) and carotid sinus nerve activity (CsNA) during spontaneous motor activity. The stimulus-response curves of AoNA and CsNA against mean arterial blood pressure (MAP) were compared between the pressor interventions evoked by spontaneous motor activity and by intravenous administration of phenylephrine or norepinephrine, in which the responses in heart rate (HR) were opposite (i.e., tachycardia vs. baroreflex bradycardia), despite the identical increase in MAP of 34-40 mmHg. In parallel to the pressor response, mean AoNA and CsNA increased similarly by 78-81 and by 88 % of the baseline control, respectively, irrespective of whether the pressor response was evoked by spontaneous motor activity or by a pharmacological intervention. The slope of the stimulus-response curve of the mean AoNA became greater (P < 0.05) during spontaneous motor activity as compared to the pharmacological intervention. On the other hand, the stimulus-response curve of the mean CsNA and its slope were equal (P > 0.05) between the two pressor interventions. Furthermore, the slopes of the stimulus-response curves of both diastolic AoNA and CsNA (defined as the minimal value within a beat) exhibited a greater increase during spontaneous motor activity. All differences in the slopes of the stimulus-response curves were abolished by restraining HR at the intrinsic cardiac frequency. In conclusion, mean mass activities of both aortic and carotid sinus baroreceptors are able to encode the beat-by-beat changes in MAP not only at rest but also during spontaneous motor activity and spontaneous motor activity-related reduction of aortic baroreceptor activity is denied
Holliday, Ezekiel S. (Inventor)
Vibrations at harmonic frequencies are reduced by injecting harmonic balancing signals into the armature of a linear motor/alternator coupled to a Stirling machine. The vibrations are sensed to provide a signal representing the mechanical vibrations. A harmonic balancing signal is generated for selected harmonics of the operating frequency by processing the sensed vibration signal with adaptive filter algorithms of adaptive filters for each harmonic. Reference inputs for each harmonic are applied to the adaptive filter algorithms at the frequency of the selected harmonic. The harmonic balancing signals for all of the harmonics are summed with a principal control signal. The harmonic balancing signals modify the principal electrical drive voltage and drive the motor/alternator with a drive voltage component in opposition to the vibration at each harmonic.
Wu, Jin-Sheng; Wang, Nan; Siniscalchi, Michael J; Perkins, Matthew H; Zheng, Yu-Tong; Yu, Wei; Chen, Song-an; Jia, Ruo-nan; Gu, Jia-Wei; Qian, Yi-Qing; Ye, Yang; Vilim, Ferdinand S; Cropper, Elizabeth C; Weiss, Klaudiusz R; Jing, Jian
Motor activity is often initiated by a population of command-like interneurons. Command-like interneurons that reliably drive programs have received the most attention, so little is known about how less reliable command-like interneurons may contribute to program generation. We study two electrically coupled interneurons, cerebral-buccal interneuron-2 (CBI-2) and CBI-11, which activate feeding motor programs in the mollusk Aplysia californica. Earlier work indicated that, in rested preparations, CBI-2, a powerful activator of programs, can trigger ingestive and egestive programs. CBI-2 reliably generated ingestive patterns only when it was repeatedly stimulated. The ability of CBI-2 to trigger motor activity has been attributed to the two program-promoting peptides it contains, FCAP and CP2. Here, we show that CBI-11 differs from CBI-2 in that it contains FCAP but not CP2. Furthermore, it is weak in its ability to drive programs. On its own, CBI-11 is therefore less effective as a program activator. When it is successful, however, CBI-11 is an effective specifier of motor activity; that is, it drives mostly ingestive programs. Importantly, we found that CBI-2 and CBI-11 complement each other's actions. First, prestimulation of CBI-2 enhanced the ability of CBI-11 to drive programs. This effect appears to be partly mediated by CP2. Second, coactivation of CBI-11 with CBI-2 makes CBI-2 programs immediately ingestive. This effect may be mediated by specific actions that CBI-11 exerts on pattern-generating interneurons. Therefore, different classes of command-like neurons in a motor network may make distinct, but potentially complementary, contributions as either activators or specifiers of motor activity.
Tanaka, Masafumi; Gaspard, Guillaume; Urakawa, Katsuya
A new concept of thrust modulation of solid propellant rocket motor is proposed. Some propellants cannot burn at intermediate pressure, while they can burn at lower and higher pressures. When one applies such a propellant to a motor, two combustion modes or two thrust levels are attainable without any change of the nozzle configuration. In the experiments different ignition conditions brought independent two combustion modes (low mode and high mode) in the same motor geometry. Some motors showed a natural transition from low mode to high mode. As an example, the alternative thrust levels were 50 N and 180 N. The natural transition was restricted with use of the partitioned grain. An active transition method was explored by exerting pressure perturbation through a vent hole with a ball valve. The valve system worked for the transition from high mode to low mode, but the reverse transition was not achieved well.
Liu, Liying; Zhang, Yongli; Yao, Qingmei
It is difficult to establish an exact mathematical model for the induction motor and the robustness is poor of the vector control system using PI regulator. This paper adopts the linear active disturbance rejection controller (LADRC) to control inductor motor. LADRC doesn't need the exact mathematical model of motor and it can not only estimate but also compensate the general disturbance that includes the coupling items in model of motor and parameters perturbations by linear extended state observer (LESO), so the rotor flux and torque fully decouple. As a result, the performance is improved. To prove the above control scheme, the proposed control system has been simulated in MATLAB/SIMULINK, and the comparison was made with PID. Simulation results show that LADRC' has better performance and robustness than PID.
King, Bradley R; Saucier, Philippe; Albouy, Genevieve; Fogel, Stuart M; Rumpf, Jost-Julian; Klann, Juliane; Buccino, Giovanni; Binkofski, Ferdinand; Classen, Joseph; Karni, Avi; Doyon, Julien
Older adults exhibit deficits in motor memory consolidation; however, little is known about the cerebral correlates of this impairment. We thus employed fMRI to investigate the neural substrates underlying motor sequence memory consolidation, and the modulatory influence of post-learning sleep, in healthy older adults. Participants were trained on a motor sequence and retested following an 8-h interval including wake or diurnal sleep as well as a 22-h interval including a night of sleep. Results demonstrated that a post-learning nap improved offline consolidation across same- and next-day retests. This enhanced consolidation was reflected by increased activity in the putamen and the medial temporal lobe, including the hippocampus, regions that have previously been implicated in sleep-dependent neural plasticity in young adults. Moreover, for the first time in older adults, the neural substrates subserving initial motor learning, including the putamen, cerebellum, and parietal cortex, were shown to forecast subsequent consolidation depending on whether a post-learning nap was afforded. Specifically, sufficient activation in a motor-related network appears to be necessary to trigger sleep-facilitated consolidation in older adults. Our findings not only demonstrate that post-learning sleep can enhance motor memory consolidation in older adults, but also provide the system-level neural correlates of this beneficial effect.
Balon, Norbert; Risso, Jean-Jacques; Blanc, François; Rostain, Jean-Claude; Weiss, Michel
Inert gas narcosis is a neurological syndrome appearing when humans or animals are exposed to hyperbaric inert gases (nitrogen, argon) composed by motor and cognitive impairments. Inert gas narcosis induces a decrease of the dopamine release at the striatum level, structure involved in the regulation of the extrapyramidal motricity. We have investigated, in freely moving rats exposed to different narcotic conditions, the relationship between the locomotor and motor activity and the striatal dopamine release, using respectively a computerized device that enables a quantitative analysis of this behavioural disturbance and voltammetry. The use of 3 MPa of nitrogen, 2 MPa of argon and 0.1 MPa of nitrous oxide, revealed after a transient phase of hyperactivity, a lower level of the locomotor and motor activity, in relation with the decrease of the striatal dopamine release. It is concluded that the striatal dopamine decrease could be related to the decrease of the locomotor and motor hyperactivity, but that other(s) neurotransmitter(s) could be primarily involved in the behavioural motor disturbances induced by narcotics. This biphasic effect could be of major importance for future pharmacological investigations, and motor categorization, on the basic mechanisms of inert gas at pressure.
Burgess, Rebecca C; Burman, Bharat; Kruhlak, Michael J; Misteli, Tom
The DNA damage response (DDR) occurs in the context of chromatin, and architectural features of chromatin have been implicated in DNA damage signaling and repair. Whereas a role of chromatin decondensation in the DDR is well established, we show here that chromatin condensation is integral to DDR signaling. We find that, in response to DNA damage chromatin regions transiently expand before undergoing extensive compaction. Using a protein-chromatin-tethering system to create defined chromatin domains, we show that interference with chromatin condensation results in failure to fully activate DDR. Conversely, forced induction of local chromatin condensation promotes ataxia telangiectasia mutated (ATM)- and ATR-dependent activation of upstream DDR signaling in a break-independent manner. Whereas persistent chromatin compaction enhanced upstream DDR signaling from irradiation-induced breaks, it reduced recovery and survival after damage. Our results demonstrate that chromatin condensation is sufficient for activation of DDR signaling and is an integral part of physiological DDR signaling.
In Nature, proteins perform functions that go well beyond controlled self-assembly at the nano scale. They are the principal components of diverse "biological machines" that can self-assemble into dynamic aggregates that achieve the cold conversion of chemical energy into motion to realize complex functions involved in cell division, cellular transport and cell motility. Nowadays, we have identified many of the proteins involved in these "molecular machines" and know much about their biochemistry, structure and biophysical behavior. Additionally, we have a rich toolbox of resources to engineer the basic dynamic working units into nanostructures to provide them with motion and the capacity to manipulate, transport, separate or sense single molecules to develop in vitro sensors and bioassays. This chapter summarizes some of the progress made in incorporating bio-molecular motors and dynamic self-organizing proteins into protein based functional nanostructures.
Vuckovich, Michael; Wright, Maynard K.; Burkett, John P.
A motor controller for a three phase AC motor (10) which is adapted to operate bidirectionally from signals received either from a computer (30) or a manual control (32). The controller is comprised of digital logic circuit means which implement a forward and reverse command signal channel (27, 29) for the application of power through the forward and reverse power switching relays (16, 18, 20, 22). The digital logic elements are cross coupled to prevent activation of both channels simultaneously and each includes a plugging circuit (65, 67) for stopping the motor upon the removal of control signal applied to one of the two channels (27, 29) for a direction of rotation desired. Each plugging circuit (65, 67) includes a one-shot pulse signal generator (88, 102) which outputs a single pulse signal of predetermined pulsewidth which is adapted to inhibit further operation of the application of power in the channel which is being activated and to apply a reversal command signal to the other channel which provides a reversed phase application of power to the motor for a period defined by the pulse-width output of the one-shot signal generator to plug the motor (10) which will then be inoperative until another rotational command signal is applied to either of the two channels.
Hamilton, Susan L.
The overall goals of this project are: 1) to define the initial signal transduction events whereby the removal of gravitational load from antigravity muscles, such as the soleus, triggers muscle atrophy, and 2) to develop countermeasures to prevent this from happening. Our rationale for this approach is that, if countermeasures can be developed to regulate these early events, we could avoid having to deal with the multiple cascades of events that occur downstream from the initial event. One of our major findings is that hind limb suspension causes an early and sustained increase in intracellular Ca(2+) concentration ([Ca (2+)](sub i)). In most cells the consequences of changes in ([Ca (2+)](sub i))depend on the amplitude, frequency and duration of the Ca(2+) signal and on other factors in the intracellular environment. We propose that muscle remodeling in microgravity represents a change in the balance among several CA(2+) regulated signal transduction pathways, in particular those involving the transcription factors NFAT and NFkB and the pro-apoptotic protein BAD. Other Ca(2+) sensitive pathways involving PKC, ras, rac, and CaM kinase II may also contribute to muscle remodeling.
Walther, Sebastian; Stegmayer, Katharina; Horn, Helge; Rampa, Luca; Razavi, Nadja; Müller, Thomas J; Strik, Werner
Schizophrenia is associated with heterogeneous course of positive and negative symptoms. In addition, reduced motor activity as measured by wrist actigraphy has been reported. However, longitudinal studies of spontaneous motor activity are missing. We aimed to explore whether activity levels were stable within and between psychotic episodes. Furthermore, we investigated the association with the course of negative symptoms. In 45 medicated patients, we investigated motor behavior within a psychotic episode. In addition, we followed 18 medicated patients across 2 episodes. Wrist actigraphy and psychopathological ratings were applied. Within an episode symptoms changed but activity levels did not vary systematically. Activity at baseline predicted the course of negative symptoms. Between two episodes activity recordings were much more stable. Again, activity at the index episode predicted the outcome of negative symptoms. In sum, spontaneous motor activity shares trait and state characteristics, the latter are associated with negative symptom course. Actigraphy may therefore become an important ambulatory instrument to monitor negative symptoms and treatment outcome in schizophrenia.
Walther, Sebastian; Stegmayer, Katharina; Horn, Helge; Rampa, Luca; Razavi, Nadja; Müller, Thomas J.; Strik, Werner
Schizophrenia is associated with heterogeneous course of positive and negative symptoms. In addition, reduced motor activity as measured by wrist actigraphy has been reported. However, longitudinal studies of spontaneous motor activity are missing. We aimed to explore whether activity levels were stable within and between psychotic episodes. Furthermore, we investigated the association with the course of negative symptoms. In 45 medicated patients, we investigated motor behavior within a psychotic episode. In addition, we followed 18 medicated patients across 2 episodes. Wrist actigraphy and psychopathological ratings were applied. Within an episode symptoms changed but activity levels did not vary systematically. Activity at baseline predicted the course of negative symptoms. Between two episodes activity recordings were much more stable. Again, activity at the index episode predicted the outcome of negative symptoms. In sum, spontaneous motor activity shares trait and state characteristics, the latter are associated with negative symptom course. Actigraphy may therefore become an important ambulatory instrument to monitor negative symptoms and treatment outcome in schizophrenia. PMID:25698981
Blackwell, Robert; Sweezy-Schindler, Oliver; Baldwin, Christopher; Hough, Loren E.; Glaser, Matthew A.; Betterton, M. D.
The cytoskeleton, despite comprising relatively few building blocks, drives an impressive variety of cellular phenomena ranging from cell division to motility. These building blocks include filaments, motor proteins, and static crosslinkers. Outside of cells, these same components can form novel materials exhibiting active flows and nonequilibrium contraction or extension. While dipolar extensile or contractile active stresses are common in nematic motor-filament systems, their microscopic origin remains unclear. Here we study a minimal physical model of filaments, crosslinking motors, and static crosslinkers to dissect the microscopic mechanisms of stress generation in a two-dimensional system of orientationally aligned rods. We demonstrate the essential role of filament steric interactions which have not previously be considered to significantly contribute to active stresses. With this insight, we are able to tune contractile or extensile behavior through control of motor-driven filament sliding and crosslinking. This work provides a roadmap for engineering stresses in active liquid crystals. The mechanisms we study may help explain why flowing nematic motor-filament mixtures are extensile while gelled systems are contractile. PMID:26742483
Horner, Richard L
Respiratory muscles with dual respiratory and non-respiratory functions (e.g. the pharyngeal and intercostal muscles) show greater suppression of activity in sleep than the diaphragm, a muscle almost entirely devoted to respiratory function. This sleep-related suppression of activity is most apparent in the tonic component of motor activity, which has functional implications of a more collapsible upper airspace in the case of pharyngeal muscles, and decreased functional residual capacity in the case of intercostal muscles. A major source of tonic drive to respiratory motoneurons originates from neurons intimately involved in states of brain arousal, i.e. neurons not classically involved in generating respiratory rhythm and pattern per se. The tonic drive to hypoglossal motoneurons, a respiratory motor pool with both respiratory and non-respiratory functions, is mediated principally by noradrenergic and glutamatergic inputs, these constituting the essential components of the wakefulness stimulus. These tonic excitatory drives are opposed by tonic inhibitory glycinergic and gamma-amino butyric acid (GABA) inputs that constrain the level of respiratory-related motor activity, with the balance determining net motor tone. In sleep, the excitatory inputs are withdrawn and GABA release into the brainstem is increased, thus decreasing respiratory motor tone and predisposing susceptible individuals to hypoventilation and obstructive sleep apnoea.
Kim, Seung-Nam; Kim, Seung-Tae; Doo, Ah-Reum; Park, Ji-Yeun; Moon, Woongjoon; Chae, Younbyoung; Yin, Chang Shik; Lee, Hyejung; Park, Hi-Joon
It has been reported that acupuncture treatment reduced dopaminergic neuron degeneration in Parkinson's disease (PD) models. However, the mechanistic pathways underlying, such neuroprotection, are poorly understood. Here, we investigated the effects and the underlying mechanism of acupuncture in a mouse model of PD using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). First, we observed that MPTP-induced impairment of Akt activation, but not MPTP-induced c-Jun activation, was effectively restored by acupuncture treatment in the substantia nigra. Furthermore, we demonstrated for the first time that the brain-specific blockade of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, by intranasal administration of LY294002, a specific inhibitor of PI3K/Akt signaling pathway, significantly blocked acupuncture-induced dopaminergic neuron protection and motor function improvement. Our results provide evidence that PI3K/Akt signaling pathway may play a central role in the mechanism underlying acupuncture-induced benefits in Parkinsonian mice.
Hayes, Spencer J; Roberts, James W; Elliott, Digby; Bennett, Simon J
The acquisition of sensorimotor parameters that control goal-directed motor behaviors occurs by observing another person in the absence of efferent and afferent motor signals. This is observational practice. During such observation, biological motion properties associated with the observed person are coded into a representation that controls motor learning. Understanding the underlying processes, specifically associated with coding biological motion, has theoretical and practical significance. Here, we examined the following questions. Experiment 1: Are the underlying velocity characteristics associated with observed biological motion kinematics imitated? Experiment 2: Is attention involved in imitating biological motion kinematics? Experiment 3: Can selective attention modulate how biological motion kinematics are imitated/represented? To this end, participants practiced by observing a model performing a movement sequence that contained typical or atypical biological motion kinematics. The differences in kinematics were designed to dissociate the movement constraints of the task and the anatomical constraints of the observer. This way, we examined whether novel motor behaviors are acquired by adopting prototypical movements or coding biological motion. The kinematic analyses indicated the timing and spatial position of peak velocity were represented. Using a dual-task protocol, we attenuated the coding of biological motion kinematics (Experiment 2) and augmented coding using a selective attention protocol (Experiment 3). Findings indicated that velocity characteristics of biological motion kinematics are coded during observational practice, most likely through bottom-up sensorimotor processes. By modulating motion coding using 2 attentional protocols, we showed that bottom-up processes are influenced by input modulation, which is consistent with top-down control during observational practice.
Stodden, David; Brian, Ali; True, Larissa; Cardon, Greet; Tallir, Isabel; Haerens, Leen
Background Positive associations between motor competence and physical activity have been identified by means of variable-centered analyses. To expand the understanding of these associations, this study used a person-centered approach to investigate whether different combinations (i.e., profiles) of actual and perceived motor competence exist (aim 1); and to examine differences in physical activity levels (aim 2) and weight status (aim 3) among children with different motor competence-based profiles. Materials and Methods Children’s (N = 361; 180 boys = 50%; Mage = 9.50±1.24yrs) actual motor competence was measured with the Test of Gross Motor Development-2 and their perceived motor competence via the Self Perception Profile for Children. We assessed physical activity via accelerometers; height through stadiometers, and weight through scales. Cluster analyses (aim 1) and MANCOVAs (aim 2 & 3) were used to analyze the data. Results The analysis generated two predictable groups: one group displaying relatively high levels of both actual (M TGMD-2 percentile = 42.54, SD = 2.33) and perceived motor competence (M = 3.42, SD = .37; high-high), and one group with relatively low levels of both (M percentile = 9.71, SD = 3.21; M PMC = 2.52, SD = .35; low-low). One additional group was also identified as having relatively low levels of actual motor competence (M percentile = 4.22, SD = 2.85) but relatively high levels of perceived motor competence (M = 3.52, SD = .30; low-high). The high-high group demonstrated higher daily physical activity (M = 48.39±2.03) and lower BMI (M = 18.13±.43) than the low-low group (MMVPA = 37.93±2.01; MBMI = 20.22±.42). The low-high group had similar physical activity-levels as the low-low group (M = 36.21±2.18) and did not significantly differ in BMI (M = 19.49±.46) from the other two groups. Conclusions A combination of high actual and perceived motor competence is related to higher physical activity and lower weight status. It is thus
Notturno, Francesca; Marzetti, Laura; Pizzella, Vittorio; Uncini, Antonino; Zappasodi, Filippo
We systematically investigated the effects of cathodal and anodal Transcranial Direct Current Stimulation (CtDCS, AtDCS) on the electric activity of primary motor cortex during a motor task. High-density electroencephalography was used to define the spatial diffusion of tDCS after effects. Ten healthy subjects performed a finger tapping task with the right hand before and after three separate sessions of 20 minutes of Sham, AtDCS or CtDCS over left primary motor cortex (M1). During movement, we found an increment of low alpha band Event-Related Desynchronization (ERD) in bilateral central, frontal areas and in the left inferior parietal region, as well as an increment of beta ERD in fronto-central and parieto-occipital regions, after AtDCs compared to Sham and CtDCS. In the rest pre-movement period, after Sham as well as AtDCS, we documented an increment of low alpha band power over the course of pre- and post-stimulation recording sessions, localized in the sensorimotor and parieto-occipital regions. On the contrary, after CtDCS no increment of low alpha power was found. Finally beta band coherence among signals from left sensorimotor cortex and activity of bilateral parietal, occipital and right frontal regions was higher after AtDCS compared with Sham condition. Similarly, theta coherence with parietal and frontal regions was enhanced after AtDCS. We hypothesize that the local modulation of membrane polarization, as well as long-lasting synaptic modification induced by tDCS over M1, could result in changes of both local band power and functional architecture of the motor network.
Wrenn, Craige C; Heitzer, Andrew M; Roth, Alexandra K; Nawrocki, Lauren; Valdovinos, Maria G
Fragile X syndrome (FXS), a disorder caused by a mutation in the FMR1 gene, is often associated with Attention Deficit Hyperactivity Disorder (ADHD). Common treatments for the hyperactivity often seen in ADHD involve the use of stimulants and α2-adrenergic agonists. The Fmr1 knockout (KO) mouse has been found to be a valid model for FXS both biologically and behaviorally. Of particular interest to our research, the Fmr1 KO mouse has been demonstrated to show increased locomotion in comparison to wild type (WT) littermates. In the present study, we assessed the effects of clonidine (0.05 mg/kg) and methylphenidate (5 mg/kg) on motor activity in Fmr1 KO mice and their WT littermates in the open field test. Results showed that methylphenidate increased motor activity in both genotypes. Clonidine decreased motor activity in both genotypes, but the effect was delayed in the Fmr1 KO mice.
Mangold, S; Läubli, T; Krueger, H
The effects of a single low alcohol dose (men 0.54 g and women 0.44 g alcohol per kg body weight) were measured by static balance, fine motor activity, and mental performance. In 10 healthy volunteers balance was registered by a temporally and spatially high resolution platform measuring the center of foot pressure and a three-dimensional coordination measurement system. Fine motor activity and mental performance were tested with selected experiments from the NES2 (Neurobehavioral Evaluation System) neuropsychological test battery. Changes of bipedal and monopedal balance could be detected after the alcohol consumption. Neither the fine motor activity nor the mental performance test demonstrated significant effects. Thus, the static balance test proved to be a sensitive, fast, and atraumatic method to identify slight neurotoxic disturbances.
Narducci, F; Bassotti, G; Gaburri, M; Morelli, A
The motor activity of the transverse, descending, and sigmoid colon was recorded for 24 hours in 14 healthy volunteers with a colonoscope positioned catheter. During the study the patients ate two 1000 kcal mixed meals and one continental breakfast. Colonic motor activity was low before meals and minimal during sleep; the motility index increased significantly after meals and at morning awakening. Most of the motor activity was represented by low amplitude contractions present singly or in bursts, which showed no recognisable pattern. All but two subjects also showed isolated high amplitude (up to 200 mmHg) contractions that propagated peristaltically over long distances at approximately 1 cm/sec. Most of these contractions occurred after morning awakening, and some in the late postprandial period, with a mean of 4.4/subject/24 h. The peristaltic contractions were often felt as an urge to defecate or preceded defecation, and could represent the manometric equivalent of the mass movements. PMID:3817580
Seydell-Greenwald, Anna; Schmidt, Thomas
Whereas physiological studies indicate that illusory contours (ICs) are signaled in early visual areas at short latencies, behavioral studies are divided as to whether IC processing can proceed in a fast, automatic, bottom-up manner or whether it requires extensive top-down intracortical feedback or even awareness and cognition. Here, we employ a…
Murakami, H; Murakami, Y
Preflight acclimatization to the rhythm of destination and postflight daytime activity are assumed to be effective countermeasures against the jet lag syndrome. Regarding this idea, resynchronization of motor activity rhythm was investigated in mice subjected to daytime exercises on a driven belt before or after the reversal of lighting regimen. In addition, the effect of prior daytime feeding was studied. No evidence was manifested that the forced exercises or feeding schedule would hasten synchronization. This result indicates that the central control system of motor activity rhythm could not be manipulated favorably by such method in mice. On the basis of the result obtained, the applicability of countermeasures to human beings was discussed.
Mugler, Emily M.; Patton, James L.; Flint, Robert D.; Wright, Zachary A.; Schuele, Stephan U.; Rosenow, Joshua; Shih, Jerry J.; Krusienski, Dean J.; Slutzky, Marc W.
Objective. Although brain-computer interfaces (BCIs) can be used in several different ways to restore communication, communicative BCI has not approached the rate or efficiency of natural human speech. Electrocorticography (ECoG) has precise spatiotemporal resolution that enables recording of brain activity distributed over a wide area of cortex, such as during speech production. In this study, we sought to decode elements of speech production using ECoG. Approach. We investigated words that contain the entire set of phonemes in the general American accent using ECoG with four subjects. Using a linear classifier, we evaluated the degree to which individual phonemes within each word could be correctly identified from cortical signal. Main results. We classified phonemes with up to 36% accuracy when classifying all phonemes and up to 63% accuracy for a single phoneme. Further, misclassified phonemes follow articulation organization described in phonology literature, aiding classification of whole words. Precise temporal alignment to phoneme onset was crucial for classification success. Significance. We identified specific spatiotemporal features that aid classification, which could guide future applications. Word identification was equivalent to information transfer rates as high as 3.0 bits s-1 (33.6 words min-1), supporting pursuit of speech articulation for BCI control.
Schneider, S; Rouffet, D M; Billaut, F; Strüder, H K
Despite modern imaging techniques, assessing and localizing changes in brain activity during whole-body exercise is still challenging. Using an active electroencephalography (EEG) system in combination with source localization algorithms, this study aimed to localize brain cortical oscillations patterns in the motor cortex and to correlate these with surface electromyography (EMG)-detected muscular activity during pedaling exercise. Eight subjects performed 2-min isokinetic (90 rpm) cycling bouts at intensities ranging from 1 to 5 Wkg(-1) body mass on a cycle ergometer. These bouts were interspersed by a minimum of 2 min of passive rest to limit to development of peripheral muscle fatigue. Brain cortical activity within the motor cortex was analyzed using a 32-channel active EEG system combined with source localization algorithms. EMG activity was recorded from seven muscles on each lower limb. EEG and EMG activity revealed comparatively stable oscillations across the different exercise intensities. More importantly, the oscillations in cortical activity within the motor cortex were significantly correlated with EMG activity during the high-intensity cycling bouts. This study demonstrates that it is possible to localize oscillations in brain cortical activity during moderate- to high-intensity cycling exercise using EEG in combination with source localization algorithms, and that these oscillations match the activity of the active muscles in time and amplitude. Results of this study might help to further evaluate the effects of central vs. peripheral fatigue during exercise.
Lancien, Frédéric; Leprince, Jérôme; Mimassi, Nagi; Mabin, Dominique; Vaudry, Hubert; Le Mével, Jean-Claude
Urotensin II (UII) has been originally isolated from fish urophysis. However, in fish as in mammals, UII is also produced in brain neurons. Although UII binding sites are widely distributed in the fish central nervous system (CNS), little is known regarding its central activities. In the present study, we have investigated the effects of intracerebroventricular (ICV) administration of synthetic trout UII on the duration of motor activity (ACT; evidenced by bursts of activity on the trace of the ventilatory signal), ventilatory frequency (VF), ventilatory amplitude (VA), and heart rate (HR) in unanesthesized trout, Oncorhynchus mykiss. ICV injection of very low doses of UII (1 and 5 pmol) produced a dose-dependent increase of ACT without affecting VF, VA, or HR. At a higher dose (50 pmol), UII stimulated ACT as well as VF, VA, and HR. ICV injection of trout angiotensin II (5 pmol) did not affect ACT, VF, and VA, but provoked a robust increase in HR. These data provide the first evidence that central administration of UII stimulates motor activity in a nonmammalian vertebrate.
Matsushita, Masafumi; Yamamoto, Ruri; Mitsui, Keiji; Kanazawa, Hiroshi
Several mammalian kinesin motor proteins exist as multiple isoforms that arise from alternative splicing of a single gene. However, the roles of many motor protein splice variants remain unclear. The kinesin-3 motor protein KIF1B has alternatively spliced isoforms distinguished by the presence or absence of insertion sequences in the conserved amino-terminal region of the protein. The insertions are located in the loop region containing the lysine-rich cluster, also known as the K-loop, and in the hinge region adjacent to the motor domain. To clarify the functions of these alternative splice variants of KIF1B, we examined the biochemical properties of recombinant KIF1B with and without insertion sequences. In a microtubule-dependent ATPase assay, KIF1B variants that contained both insertions had higher activity and affinity for microtubules than KIF1B variants that contained no insertions. Mutational analysis of the K-loop insertion revealed that variants with a longer insertion sequence at this site had higher activity. However, the velocity of movement in motility assays was similar between KIF1B with and without insertion sequences. Our results indicate that splicing isoforms of KIF1B that vary in their insertion sequences have different motor activities.
Sim, Eun-Jin; Helbig, Hannah B; Graf, Markus; Kiefer, Markus
Recent evidence suggests an interaction between the ventral visual-perceptual and dorsal visuo-motor brain systems during the course of object recognition. However, the precise function of the dorsal stream for perception remains to be determined. The present study specified the functional contribution of the visuo-motor system to visual object recognition using functional magnetic resonance imaging and event-related potential (ERP) during action priming. Primes were movies showing hands performing an action with an object with the object being erased, followed by a manipulable target object, which either afforded a similar or a dissimilar action (congruent vs. incongruent condition). Participants had to recognize the target object within a picture-word matching task. Priming-related reductions of brain activity were found in frontal and parietal visuo-motor areas as well as in ventral regions including inferior and anterior temporal areas. Effective connectivity analyses suggested functional influences of parietal areas on anterior temporal areas. ERPs revealed priming-related source activity in visuo-motor regions at about 120 ms and later activity in the ventral stream at about 380 ms. Hence, rapidly initiated visuo-motor processes within the dorsal stream functionally contribute to visual object recognition in interaction with ventral stream processes dedicated to visual analysis and semantic integration.
Krneta, Željko; Casals, Cristina; Bala, Gustav; Madić, Dejan; Pavlović, Slobodan; Drid, Patrik
The purpose of this study was to evaluate the effects of an additional, organized, and more intensive kinesiological treatment on "pure" motor abilities in preschool children. In the present study an experimental treatment was carried out on a sample of 37 preschool boys by applying kinesiological activities. The 60 minute treatment was applied over a period of one school year (9 months), twice a week. A control group of 31 boys were trained according to the regular program for preschool institutions. Treatment effects were assessed by 8 motor ability tests and 5 anthropometric measures. The significant differences between the groups, which were observed after the final measurement and compared to the initial one, proved that the kinesiological treatment had a positive impact on the general development of "pure" motor abilities. The most significant effect of experimental kinesiological treatment was the improvement in whole body force, flexibility and coordination of preschool boys. These findings, obtained only in one school year, point to the importance of physical exercise and the application of additional kinesiological activities with various modalities, to improve motor development, even morphological growth and development in preschool children. The effects of the perennial application of kinesiological activities, under the supervision of kinesiological professionals, could be beneficial and could form the basis for a better biological and motor development in older age.
Snider, Jon; Müller, Martijn L.T.M; Kotagal, Vikas; Koeppe, Robert A; Scott, Peter J.H.; Frey, Kirk A; Albin, Roger L.; Bohnen, Nicolaas I.
Objective To investigate the relationship between time spent in non-exercise and exercise physical activity and severity of motor functions in Parkinson disease (PD). Background Increasing motor impairments of PD incline many patients to a sedentary lifestyle. We investigated the relationship between duration of both non-exercise and exercise physical activity over a 4-week period using the Community Health Activities Model Program for Seniors (CHAMPS) questionnaire and severity of clinical motor symptoms in PD. We accounted for the magnitude of nigrostriatal degeneration. Methods Cross-sectional study. PD subjects, n=48 (40M); 69.4±7.4 (56–84) years old; 8.4±4.2 (2.5–20) years motor disease duration, mean UPDRS motor score 27.5 ± 10.3 (7–53) and mean MMSE score 28.4 ± 1.9 (22–30) underwent [11C]dihydrotetrabenazine (DTBZ) PET imaging to assess nigrostriatal denervation and completed the CHAMPS questionnaire and clinical assessment. Results Bivariate correlations showed an inverse relationship between motor UPDRS severity scores and duration of non-exercise physical activity (R= −0.37, P=0.0099) but not with duration of exercise physical activity (R= −0.05, P= 0.76) over 4 weeks. Multiple regression analysis using UPDRS motor score as outcome variable demonstrated a significant regressor effect for duration of non-exercise physical activity (F=6.15, P=0.017) while accounting for effects of nigrostriatal degeneration (F=4.93, P=0.032), levodopa-equivalent dose (LED; F=1.07, P=0.31), age (F=4.37, P=0.043) and duration of disease (F=1.46, P=0.23; total model (F=5.76, P=0.0004). Conclusions Non-exercise physical activity is a correlate of motor symptom severity in PD independent of the magnitude of nigrostriatal degeneration. Non-exercise physical activity may have positive effects on functional performance in PD. PMID:26330028
Alekseeva, E V; Popova, T S; Sal'nikov, P S
The review include actual facts, demonstrating high probability of glutamatergic neurotransmitter system role in the regulation of the gastrointestinal tract motor activity. These facts suggest significant role of the glutamatergic neurotransmitter system dysfunction in forming motor activity disorders of the digestive tract, including in patients in critical condition. The analysis is based on results of multiple experimental and clinical researches of glutamic acid and other components of the glutamatergic neurotransmitter system in central nervous system and autonomic nervous system (with the accent on the enteral nervous system) in normal conditions and with functioning changes of the glutamatergic neurotransmitter system in case of inflammation, hupoxia, stress and in critical condition.
Roy, François D; Gibson, Grady; Stein, Richard B
Percutaneous spinal stimulation is a promising new technique for understanding human spinal reflexes and for evaluating the pathophysiology of motor roots. Previous studies have generally stimulated the T11/T12 or T12/L1 vertebral junctions, sites that overlie the lumbosacral enlargement. The present study sought to determine the best location for targeting sensory and motor roots during sitting. We used paired stimuli, 50 ms apart, to distinguish the contribution of the reflex and motor components which make up the root evoked potential. This assumed that post-stimulation attenuation, primarily through homosynaptic depression, would abolish the second potential if it was trans-synaptic in origin. Conversely, successive responses would be unchanged if motor roots were being stimulated. Here, we show that sensory root reflexes were optimally elicited with percutaneous stimulation over the L1-L3 vertebrae. However, the optimal position varied between subjects and depended on the target muscle being studied. A collision test showed that the reflex recorded in pre-tibial flexors was low in amplitude and was prone to crosstalk from neighbouring muscles. In contrast to the reflex response, direct motor root activation was optimal with stimulation over the more caudal L5-S1 vertebrae. The present results support the utility of paired stimulation for evaluating the topographical recruitment of sensory and motor roots to human leg muscles.
Kösem, Süleyman; Ökten, Zeynep; Ho, Thi-Hieu; Trommler, Gudrun; Koonce, Michael P; Samereier, Matthias; Müller-Taubenberger, Annette
Kinesins are ATP-dependent molecular motors that mediate unidirectional intracellular transport along microtubules. Dictyostelium discoideum has 13 different kinesin isoforms including two members of the kinesin-7 family, Kif4 and Kif11. While Kif4 is structurally and functionally related to centromere-associated CENP-E proteins involved in the transport of chromosomes to the poles during mitosis, the function of the unusually short CENP-E variant Kif11 is unclear. Here we show that orthologs of short CENP-E variants are present in plants and fungi, and analyze functional properties of the Dictyostelium CENP-E version, Kif11. Gene knockout mutants reveal that Kif11 is not required for mitosis or development. Imaging of GFP-labeled Kif11 expressing Dictyostelium cells indicates that Kif11 is a plus-end directed motor that accumulates at microtubule plus ends. By multiple motor gliding assays, we show that Kif11 moves with an average velocity of 38nm/s, thus defining Kif11 as a very slow motor. The activity of the Kif11 motor appears to be modulated via interactions with the non-catalytic tail region. Our work highlights a subclass of kinesin-7-like motors that function outside of a role in mitosis.
D'Heygère, François; Schwartz, Annie; Coste, Franck; Castaing, Bertrand; Boudvillain, Marc
The bacterial transcription termination factor Rho-a ring-shaped molecular motor displaying directional, ATP-dependent RNA helicase/translocase activity-is an interesting therapeutic target. Recently, Rho from Mycobacterium tuberculosis (MtbRho) has been proposed to operate by a mechanism uncoupled from molecular motor action, suggesting that the manner used by Rho to dissociate transcriptional complexes is not conserved throughout the bacterial kingdom. Here, however, we demonstrate that MtbRho is a bona fide molecular motor and directional helicase which requires a catalytic site competent for ATP hydrolysis to disrupt RNA duplexes or transcription elongation complexes. Moreover, we show that idiosyncratic features of the MtbRho enzyme are conferred by a large, hydrophilic insertion in its N-terminal 'RNA binding' domain and by a non-canonical R-loop residue in its C-terminal 'motor' domain. We also show that the 'motor' domain of MtbRho has a low apparent affinity for the Rho inhibitor bicyclomycin, thereby contributing to explain why M. tuberculosis is resistant to this drug. Overall, our findings support that, in spite of adjustments of the Rho motor to specific traits of its hosting bacterium, the basic principles of Rho action are conserved across species and could thus constitute pertinent screening criteria in high-throughput searches of new Rho inhibitors.
Guo, Xinyao; Xiang, Jing; Wang, Yingying; O'Brien, Hope; Kabbouche, Marielle; Horn, Paul; Powers, Scott W; Hershey, Andrew D
Migraine attacks have been shown to interfere with normal function in the brain such as motor or sensory function. However, to date, there has been no clinical neurophysiology study focusing on the motor function in children with migraine during headache attacks. To investigate the motor function in children with migraine, twenty-six children with acute migraine, meeting International Classification of Headache Disorders criteria and age- and gender-matched healthy children were studied using a 275-channel magnetoencephalography system. A finger-tapping paradigm was designed to elicit neuromagnetic activation in the motor cortex. Children with migraine showed significantly prolonged latency of movement-evoked magnetic fields (MEF) during finger movement compared with the controls. The correlation coefficient of MEF latency and age in children with migraine was significantly different from that in healthy controls. The spectral power of high gamma (65-150 Hz) oscillations during finger movement in the primary motor cortex is also significantly higher in children with migraine than in controls. The alteration of responding latency and aberrant high gamma oscillations suggest that the developmental trajectory of motor function in children with migraine is impaired during migraine attacks and/or developmentally delayed. This finding indicates that childhood migraine may affect the development of brain function and result in long-term problems.
Vafina, E Z; Abzalov, R A; Abzalov, N I; Nikitin, A S; Gulyakov, A A
We analyzed parameters of the pumping function of the heart in rats subjected to enhanced motor activity after a preliminary 70-day hypokinesia under conditions of α- and β-adrenergic receptor stimulation with norepinephrine followed by blockade of β-adrenergic receptor with propranolol (obsidian) and α1-adrenergic receptors with doxazosin. After norepinephrine administration, the HR and cardiac output were higher in rats with enhanced physical activity after preliminary hypokinesia than in rats with low physical activity. After propranolol administration, stroke volume and cardiac output in 100-day-old rats with limited activity were lower, and HR higher was than in rats with enhanced physical activity after preliminary 70-day hypokinesia. After administration of doxazosin, rats with limited motor activity demonstrated more pronounced changes in HR than rats with enhanced physical activity after preliminary 70-day hypokinesia.
Thompson, Debra S.
In recognition of the close relationship between motor skill and cognitive development in the first 2 years of life, this guide presents 78 developmentally appropriate activities that parents and teachers can use to enhance infant and toddler motor development. Activities are categorized by age group as follows: (1) 16 activities for newborn to…
Grimonprez, Annelies; Raedt, Robrecht; De Taeye, Leen; Larsen, Lars Emil; Delbeke, Jean; Boon, Paul; Vonck, Kristl
Vagus nerve stimulation (VNS) is a treatment for refractory epilepsy and depression. Previous studies using invasive recording electrodes showed that VNS induces laryngeal motor-evoked potentials (LMEPs) through the co-activation of the recurrent laryngeal nerve and subsequent contractions of the laryngeal muscles. The present study investigates the feasibility of recording LMEPs in chronically VNS-implanted rats, using a minimally-invasive technique, to assess effective current delivery to the nerve and to determine optimal VNS output currents for vagal fiber activation. Three weeks after VNS electrode implantation, signals were recorded using an electromyography (EMG) electrode in the proximity of the laryngeal muscles and a reference electrode on the skull. The VNS output current was gradually ramped up from 0.1 to 1.0 mA in 0.1 mA steps. In 13/27 rats, typical LMEPs were recorded at low VNS output currents (median 0.3 mA, IQR 0.2-0.3 mA). In 11/27 rats, significantly higher output currents were required to evoke electrophysiological responses (median 0.7 mA, IQR 0.5-0.7 mA, p < 0.001). The latencies of these responses deviated significantly from LMEPs (p < 0.05). In 3/27 rats, no electrophysiological responses to simulation were recorded. Minimally invasive LMEP recordings are feasible to assess effective current delivery to the vagus nerve. Furthermore, our results suggest that low output currents are sufficient to activate vagal fibers.
González-Franco, Mar; Peck, Tabitha C; Rodríguez-Fornells, Antoni; Slater, Mel
We report an experiment where participants observed an attack on their virtual body as experienced in an immersive virtual reality (IVR) system. Participants sat by a table with their right hand resting upon it. In IVR, they saw a virtual table that was registered with the real one, and they had a virtual body that substituted their real body seen from a first person perspective. The virtual right hand was collocated with their real right hand. Event-related brain potentials were recorded in two conditions, one where the participant's virtual hand was attacked with a knife and a control condition where the knife only struck the virtual table. Significantly greater P450 potentials were obtained in the attack condition confirming our expectations that participants had a strong illusion of the virtual hand being their own, which was also strongly supported by questionnaire responses. Higher levels of subjective virtual hand ownership correlated with larger P450 amplitudes. Mu-rhythm event-related desynchronization in the motor cortex and readiness potential (C3-C4) negativity were clearly observed when the virtual hand was threatened-as would be expected, if the real hand was threatened and the participant tried to avoid harm. Our results support the idea that event-related potentials may provide a promising non-subjective measure of virtual embodiment. They also support previous experiments on pain observation and are placed into context of similar experiments and studies of body perception and body ownership within cognitive neuroscience.
Roy, Serge H; Cole, Bryan T; Gilmore, L Don; De Luca, Carlo J; Thomas, Cathi A; Saint-Hilaire, Marie M; Nawab, S Hamid
Parkinson's disease (PD) can present with a variety of motor disorders that fluctuate throughout the day, making assessment a challenging task. Paper-based measurement tools can be burdensome to the patient and clinician and lack the temporal resolution needed to accurately and objectively track changes in motor symptom severity throughout the day. Wearable sensor-based systems that continuously monitor PD motor disorders may help to solve this problem, although critical shortcomings persist in identifying multiple disorders at high temporal resolution during unconstrained activity. The purpose of this study was to advance the current state of the art by (1) introducing hybrid sensor technology to concurrently acquire surface electromyographic (sEMG) and accelerometer data during unconstrained activity and (2) analyzing the data using dynamic neural network algorithms to capture the evolving temporal characteristics of the sensor data and improve motor disorder recognition of tremor and dyskinesia. Algorithms were trained (n=11 patients) and tested (n=8 patients; n=4 controls) to recognize tremor and dyskinesia at 1-second resolution based on sensor data features and expert annotation of video recording during 4-hour monitoring periods of unconstrained daily activity. The algorithms were able to make accurate distinctions between tremor, dyskinesia, and normal movement despite the presence of diverse voluntary activity. Motor disorder severity classifications averaged 94.9% sensitivity and 97.1% specificity based on 1 sensor per symptomatic limb. These initial findings indicate that new sensor technology and software algorithms can be effective in enhancing wearable sensor-based system performance for monitoring PD motor disorders during unconstrained activities.
Cusso, Melanie E; Donald, Kenneth J; Khoo, Tien K
Parkinson's disease (PD) is a neurological disorder that is associated with both motor and non-motor symptoms (NMS). The management of PD is primarily via pharmaceutical treatment; however, non-pharmaceutical interventions have become increasingly recognized in the management of motor and NMS. In this review, the efficacy of physical activity, including physiotherapy and occupational therapy, as an intervention in NMS will be assessed. The papers were extracted between the 20th and 22nd of June 2016 from PubMed, Web of Science, Medline, Ovid, SportsDiscuss, and Scopus using the MeSH search terms "Parkinson's," "Parkinson," and "Parkinsonism" in conjunction with "exercise," "physical activity," "physiotherapy," "occupational therapy," "physical therapy," "rehabilitation," "dance," and "martial arts." Twenty studies matched inclusion criteria of having 10 or more participants with diagnosed idiopathic PD participating in the intervention as well as having to evaluate the effects of physical activity on NMS in PD as controlled, randomized intervention studies. The outcomes of interest were NMS, including depression, cognition, fatigue, apathy, anxiety, and sleep. Risk of bias in the studies was evaluated using the Cochrane Collaboration's tool for assessing risk of bias. Comparability of the various intervention methods, however, was challenging due to demographic variability and methodological differences. Nevertheless, physical activity can positively impact the global NMS burden including depression, apathy, fatigue, day time sleepiness, sleep, and cognition, thus supporting its therapeutic potential in neurodegenerative conditions such as PD. It is recommended that further adequately powered studies are conducted to assess the therapeutic role of physical activity on both motor and non-motor aspects of PD. These studies should be optimally designed to assess non-motor elements of disease using instruments validated in PD.
Prasad, Abhishek; Sahin, Mesut
Injury at the cervical region of the spinal cord results in the loss of the skeletal muscle control from below the shoulders and hence causes quadriplegia. The brain-computer interface technique is one way of generating a substitute for the lost command signals in these severely paralyzed individuals using the neural signals from the brain. In this study, we are investigating the feasibility of an alternative method where the volitional signals are extracted from the cervical spinal cord above the point of injury. A microelectrode array assembly was implanted chronically at the C5-C6 level of the spinal cord in rats. Neural recordings were made during the face cleaning behavior with forelimbs as this task involves cyclic forelimb movements and does not require any training. The correlation between the volitional motor signals and the elbow movements was studied. Linear regression technique was used to reconstruct the arm movement from the rectified-integrated version of the principal neural components. The results of this study demonstrate the feasibility of extracting the motor signals from the cervical spinal cord and using them for reconstruction of the elbow movements.
Huang, Pengxiang; Nedelcu, Daniel; Watanabe, Miyako; Jao, Cindy; Kim, Youngchang; Liu, Jing; Salic, Adrian
In vertebrates, sterols are necessary for Hedgehog signaling, a pathway critical in embryogenesis and cancer. Sterols activate the membrane protein Smoothened by binding its extracellular, cysteine-rich domain (CRD). Major unanswered questions concern the nature of the endogenous, activating sterol and the mechanism by which it regulates Smoothened. We report crystal structures of CRD complexed with sterols and alone, revealing that sterols induce a dramatic conformational change of the binding site, which is sufficient for Smoothened activation and is unique among CRD-containing receptors. We demonstrate that Hedgehog signaling requires sterol binding to Smoothened and define key residues for sterol recognition and activity. We also show that cholesterol itself binds and activates Smoothened. Furthermore, the effect of oxysterols is abolished in Smoothened mutants that retain activation by cholesterol and Hedgehog. We propose that the endogenous Smoothened activator is cholesterol, not oxysterols, and that vertebrate Hedgehog signaling controls Smoothened by regulating its access to cholesterol.
Nakagawa, Akito; Naito, Atsuhiko T.; Sumida, Tomokazu; Nomura, Seitaro; Shibamoto, Masato; Higo, Tomoaki; Okada, Katsuki; Sakai, Taku; Hashimoto, Akihito; Kuramoto, Yuki; Oka, Toru; Lee, Jong-Kook; Harada, Mutsuo; Ueda, Kazutaka; Shiojima, Ichiro; Limbourg, Florian P.; Adams, Ralf H.; Noda, Tetsuo; Sakata, Yasushi; Akazawa, Hiroshi; Komuro, Issei
Activation of β-catenin-dependent canonical Wnt signaling in endothelial cells plays a key role in angiogenesis during development and ischemic diseases, however, other roles of Wnt/β-catenin signaling in endothelial cells remain poorly understood. Here, we report that sustained activation of β-catenin signaling in endothelial cells causes cardiac dysfunction through suppressing neuregulin-ErbB pathway in the heart. Conditional gain-of-function mutation of β-catenin, which activates Wnt/β-catenin signaling in Bmx-positive arterial endothelial cells (Bmx/CA mice) led to progressive cardiac dysfunction and 100% mortality at 40 weeks after tamoxifen treatment. Electron microscopic analysis revealed dilatation of T-tubules and degeneration of mitochondria in cardiomyocytes of Bmx/CA mice, which are similar to the changes observed in mice with decreased neuregulin-ErbB signaling. Endothelial expression of Nrg1 and cardiac ErbB signaling were suppressed in Bmx/CA mice. The cardiac dysfunction of Bmx/CA mice was ameliorated by administration of recombinant neuregulin protein. These results collectively suggest that sustained activation of Wnt/β-catenin signaling in endothelial cells might be a cause of heart failure through suppressing neuregulin-ErbB signaling, and that the Wnt/β-catenin/NRG axis in cardiac endothelial cells might become a therapeutic target for heart failure. PMID:27146149
Szturm, Tony; Polyzoi, Eleoussa; Marotta, Jonathan; Srikesavan, Cynthia Swarnalatha
This article introduces a game-based rehabilitation platform designed to integrate training of fine motor skills and cognitive functions. A novel computer interface device was developed that can effectively replace a standard computer mouse when doing exercises to rehabilitate hand function. This smart device converts signals from miniature motion sensors to signals equivalent to that of a computer mouse. In this way, nearly any object or utensil can be changed to function exactly as a computer mouse, simply by attaching the motion sensor. Multiple objects with varied sizes, shapes, weights, and functional demands for precision can be used for exercise and to practice a variety of gross or fine motor skills, and, importantly, while playing fun computer games. The platform was designed to work with modern and common computer games, which have a broad range of movement speeds and accuracy levels, cognitive activities (puzzles, choices, distractors), and educational content. The platform includes a designed assessment game with advanced data logging for electronic monitoring. Data analysis methods have been developed to quantify performance metrics that provide insights into the quality, efficiency, and skill of a child and thus mean to conduct trend analyses that indicate how the child is performing over time.
Cheung, Vincent C. K.; d'Avella, Andrea; Bizzi, Emilio
It has been suggested that the motor system may circumvent the difficulty of controlling many degrees of freedom in the musculoskeletal apparatus by generating motor outputs through a combination of discrete muscle synergies. How a discretely organized motor system compensates for diverse perturbations has remained elusive. Here, we investigate whether motor responses observed after an inertial-load perturbation can be generated by altering the recruitment of synergies normally used for constructing unperturbed movements. Electromyographic (EMG, 13 muscles) data were collected from the bullfrog hindlimb during natural behaviors before, during, and after the same limb was loaded by a weight attached to the calf. Kinematic analysis reveals the absence of aftereffect on load removal, suggesting that load-related EMG changes were results of immediate motor pattern adjustments. We then extracted synergies from EMGs using the nonnegative matrix factorization algorithm and developed a procedure for assessing the extent of synergy sharing across different loading conditions. Most synergies extracted were found to be activated in all loaded and unloaded conditions. However, for certain synergies, the amplitude, duration, and/or onset time of their activation bursts were up- or down-modulated during loading. Behavioral parameterizations reveal that load-related modulation of synergy activations depended on the behavioral variety (e.g., kick direction and amplitude) and the movement phase performed. Our results suggest that muscle synergies are robust across different dynamic conditions and immediate motor adjustments can be accomplished by modulating synergy activations. An appendix describes the novel procedure we developed, useful for discovering shared and specific features from multiple data sets. PMID:19091930
Helmich, Rick C; Bloem, Bastiaan R; Toni, Ivan
Parkinson's disease (PD) is surprisingly heterogeneous: some patients have a prominent resting tremor, while others never develop this symptom. Here we investigate whether the functional organization of the voluntary motor system differs between PD patients with and without resting tremor, and whether these differences relate to the cerebral circuit producing tremor. We compared 18 PD patients with marked tremor, 20 PD patients without tremor, and 19 healthy controls. Subjects performed a controlled motor imagery task during fMRI scanning. We quantified imagery-related cerebral activity by contrasting imagery of biomechanically difficult and easy movements. Tremor-related activity was identified by relating cerebral activity to fluctuations in tremor amplitude, using electromyography during scanning. PD patients with tremor had better behavioral performance than PD patients without tremor. Furthermore, tremulous PD patients showed increased imagery-related activity in somatosensory area 3a, as compared with both healthy controls and to nontremor PD patients. This effect was independent from tremor-related activity, which was localized to the motor cortex, cerebellum, and thalamic ventral intermediate nucleus (VIM). The VIM, with known projections to area 3a, was unique in showing both tremor- and imagery-related responses. We conclude that parkinsonian tremor influences motor imagery by modulating central somatosensory processing through the VIM. This mechanism may explain clinical differences between PD patients with and without tremor.
Bursian, A V; Dmitrieva, L E
In ontogenesis of rats, similar to many other animals, in the development of the spontaneous motor activity two qualitatively different stages are observed. The first one is characterized by periodic, mainly sensor-independent generalized motor excitation which at the second stage is substituted by stereotypic specialized motor programs (locomotion, grooming). Both stages exhibit similar age dynamics: the increase in the activity, its maximum and subsequent inhibition with a shift of the corresponding phases for about two weeks. This dynamics is mainly associated with heterochronous maturation of excitatory and inhibitory systems of regulation of the nervous activity. Change in the stages depends on changes of functional role of motor activity in ontogenesis from mainly morphogenetic one (and promotion of a necessary level of vegetative functions) to directional behavior. Inhibition at the first stage results in deep functional rearrangement in the central nervous system serving as a background for the onset of specialized behavioural activity. The development of the latter is also excessive, the subsequent inhibition being less deep and reversible.
Khan, Bilal; Chand, Pankaj; Alexandrakis, George
Functional near infrared (fNIR) imaging was used to identify spatiotemporal relations between spatially distinct cortical regions activated during various hand and arm motion protocols. Imaging was performed over a field of view (FOV, 12 x 8.4 cm) including the secondary motor, primary sensorimotor, and the posterior parietal cortices over a single brain hemisphere. This is a more extended FOV than typically used in current fNIR studies. Three subjects performed four motor tasks that induced activation over this extended FOV. The tasks included card flipping (pronation and supination) that, to our knowledge, has not been performed in previous functional magnetic resonance imaging (fMRI) or fNIR studies. An earlier rise and a longer duration of the hemodynamic activation response were found in tasks requiring increased physical or mental effort. Additionally, analysis of activation images by cluster component analysis (CCA) demonstrated that cortical regions can be grouped into clusters, which can be adjacent or distant from each other, that have similar temporal activation patterns depending on whether the performed motor task is guided by visual or tactile feedback. These analyses highlight the future potential of fNIR imaging to tackle clinically relevant questions regarding the spatiotemporal relations between different sensorimotor cortex regions, e.g. ones involved in the rehabilitation response to motor impairments. PMID:22162826
Robinson, Leah E.; Palmer, Kara K.; Bub, Kristen L.
Self-regulatory skills are broadly defined as the ability to manage emotions, focus attention, and inhibit some behaviors while activating others in accordance with social expectations and are an established indicator of academic success. Growing evidence links motor skills and physical activity to self-regulation. This study examined the efficacy of a motor skills intervention (i.e., the Children’s Health Activity Motor Program, CHAMP) that is theoretically grounded in Achievement Goal Theory on motor skill performance and self-regulation in Head Start preschoolers. A sample of 113 Head Start preschoolers (Mage = 51.91 ± 6.5 months; 49.5% males) were randomly assigned to a treatment (n = 68) or control (n = 45) program. CHAMP participants engaged in 15, 40-min sessions of a mastery climate intervention that focused on the development of motor skills over 5 weeks while control participants engaged in their normal outdoor recess period. The Delay of Gratification Snack Task was used to measure self-regulation and the Test of Gross Motor Development-2nd Edition was used to assess motor skills. All measures were assessed prior to and following the intervention. Linear mixed models were fit for both self-regulation and motor skills. Results revealed a significant time × treatment interaction (p < 0.001). In regard to motor skills, post hoc comparisons found that all children improved their motor skills (p < 0.05), but the CHAMP group improved significantly more than the control group (p < 0.001). Children in CHAMP maintained their self-regulation scores across time, while children in the control group scored significantly lower than the CHAMP group at the posttest (p < 0.05). CHAMP is a mastery climate movement program that enhance skills associated with healthy development in children (i.e., motor skills and self-regulation). This efficacy trial provided evidence that CHAMP helped maintain delay of gratification in preschool
Robinson, Leah E; Palmer, Kara K; Bub, Kristen L
Self-regulatory skills are broadly defined as the ability to manage emotions, focus attention, and inhibit some behaviors while activating others in accordance with social expectations and are an established indicator of academic success. Growing evidence links motor skills and physical activity to self-regulation. This study examined the efficacy of a motor skills intervention (i.e., the Children's Health Activity Motor Program, CHAMP) that is theoretically grounded in Achievement Goal Theory on motor skill performance and self-regulation in Head Start preschoolers. A sample of 113 Head Start preschoolers (Mage = 51.91 ± 6.5 months; 49.5% males) were randomly assigned to a treatment (n = 68) or control (n = 45) program. CHAMP participants engaged in 15, 40-min sessions of a mastery climate intervention that focused on the development of motor skills over 5 weeks while control participants engaged in their normal outdoor recess period. The Delay of Gratification Snack Task was used to measure self-regulation and the Test of Gross Motor Development-2nd Edition was used to assess motor skills. All measures were assessed prior to and following the intervention. Linear mixed models were fit for both self-regulation and motor skills. Results revealed a significant time × treatment interaction (p < 0.001). In regard to motor skills, post hoc comparisons found that all children improved their motor skills (p < 0.05), but the CHAMP group improved significantly more than the control group (p < 0.001). Children in CHAMP maintained their self-regulation scores across time, while children in the control group scored significantly lower than the CHAMP group at the posttest (p < 0.05). CHAMP is a mastery climate movement program that enhance skills associated with healthy development in children (i.e., motor skills and self-regulation). This efficacy trial provided evidence that CHAMP helped maintain delay of gratification in preschool
Lee, Taraz G.; Grafton, Scott T.
There are three non-exclusive theoretical explanations for the paradoxical collapse of performance due to large financial incentives. It has been proposed that “choking under pressure” is either due to distraction, interference via an increase in top-down control and performance monitoring, or excessive levels of arousal in the face of large losses. Given the known neural architecture involved in executive control and reward, we used fMRI of human participants during incentivized motor performance to provide evidence to support and/or reconcile these competing models in a visuomotor task. We show that the execution of a pre-trained motor task during neuroimaging is impaired by high rewards. BOLD activity occurring prior to movement onset is increased in dorsolateral prefrontal cortex and functional connectivity between this region and motor cortex is likewise increased just prior to choking. However, the extent of this increase in functional connectivity is inversely related to a participant's propensity to choke, suggesting that a failure in exerting top-down influence on motor control underlies choking under pressure due to large incentives. These results are consistent with a distraction account of choking and suggest that frontal influences on motor activity are necessary to protect performance from vulnerability under pressure. PMID:25449744
Atkinson, Darryn A.; Dy, Christine J.; Gurley, Katelyn M.; Smith, Valerie L.; Angeli, Claudia; Harkema, Susan J.; Edgerton, V. Reggie; Gerasimenko, Yury P.
Transcutaneous and epidural electrical spinal cord stimulation techniques are becoming more valuable as electrophysiological and clinical tools. Recently, we observed selective activation of proximal and distal motor pools during epidural spinal stimulation. In the present study, we hypothesized that the characteristics of recruitment curves obtained from leg muscles will reflect a relative preferential activation of proximal and distal motor pools based on their arrangement along the lumbosacral enlargement. The purpose was to describe the electrophysiological responses to transcutaneous stimulation in leg muscles innervated by motoneurons from different segmental levels. Stimulation delivered along the rostrocaudal axis of the lumbosacral enlargement in the supine position resulted in a selective topographical recruitment of proximal and distal leg muscles, as described by threshold intensity, slope of the recruitment curves, and plateau point intensity and magnitude. Relatively selective recruitment of proximal and distal motor pools can be titrated by optimizing the site and intensity level of stimulation to excite a given combination of motor pools. The slope of the recruitment of particular muscles allows characterization of the properties of afferents projecting to specific motoneuron pools, as well as to the type and size of the motoneurons. The location and intensity of transcutaneous spinal electrical stimulation are critical to target particular neural structures across different motor pools in investigation of specific neuromodulatory effects. Finally, the asymmetry in bilateral evoked potentials is inevitable and can be attributed to both anatomical and functional peculiarities of individual muscles or muscle groups. PMID:25814642
Lee, Taraz G; Grafton, Scott T
There are three non-exclusive theoretical explanations for the paradoxical collapse of performance due to large financial incentives. It has been proposed that "choking under pressure" is either due to distraction, interference via an increase in top-down control and performance monitoring, or excessive levels of arousal in the face of large losses. Given the known neural architecture involved in executive control and reward, we used fMRI of human participants during incentivized motor performance to provide evidence to support and/or reconcile these competing models in a visuomotor task. We show that the execution of a pre-trained motor task during neuroimaging is impaired by high rewards. BOLD activity occurring prior to movement onset is increased in dorsolateral prefrontal cortex and functional connectivity between this region and motor cortex is likewise increased just prior to choking. However, the extent of this increase in functional connectivity is inversely related to a participant's propensity to choke, suggesting that a failure in exerting top-down influence on motor control underlies choking under pressure due to large incentives. These results are consistent with a distraction account of choking and suggest that frontal influences on motor activity are necessary to protect performance from vulnerability under pressure.
Neyedli, Heather F; Sampaio-Baptista, Cassandra; Kirkman, Matthew A; Havard, David; Lührs, Michael; Ramsden, Katie; Flitney, David D; Clare, Stuart; Goebel, Rainer; Johansen-Berg, Heidi
Neurofeedback training involves presenting an individual with a representation of their brain activity and instructing them to alter the activity using the feedback. One potential application of neurofeedback is for patients to alter neural activity to improve function. For example, there is evidence that greater laterality of movement-related activity is associated with better motor outcomes after stroke; so using neurofeedback to increase laterality may provide a novel route for improving outcomes. However, we must demonstrate that individuals can control relevant neurofeedback signals. Here, we performed two proof-of-concept studies, one in younger (median age: 26years) and one in older healthy volunteers (median age: 67.5years). The purpose was to determine if participants could manipulate laterality of activity between the motor cortices using real-time fMRI neurofeedback while performing simple hand movements. The younger cohort trained using their left and right hand, the older group trained using their left hand only. In both studies participants in a neurofeedback group were able to achieve more lateralized activity than those in a sham group (younger adults: F(1,23)=4.37, p<0.05; older adults: F(1,15)=9.08, p<0.01). Moreover, the younger cohort was able to maintain the lateralized activity for right hand movements once neurofeedback was removed. The older cohort did not maintain lateralized activity upon feedback removal, with the limitation being that they did not train with their right hand. The results provide evidence that neurofeedback can be used with executed movements to promote lateralized brain activity and thus is amenable for testing as a therapeutic intervention for patients following stroke.
Piché, M; Arsenault, M; Rainville, P
In the past two decades, functional brain imaging has considerably advanced our knowledge of cerebral pain processing. However, many important links are still missing in our understanding of brain activity in relation to the regulation of pain-related physiological responses. This fMRI study investigates the cerebral correlates of pain (rating), motor responses (RIII-reflex) and autonomic activity (skin conductance response; SCR) evoked by noxious electrical stimulation. Stimulus intensity was adjusted individually based on the RIII threshold to control for differences in peripheral processes and baseline spinal activation. Covariance analyses were used to reveal individual differences in brain activity uniquely associated with individual differences in pain, RIII and SCR. Shock-evoked activity in cingulate, medial orbitofrontal and parahippocampal regions predicted pain sensitivity. Moreover, lateral orbitofrontal and cingulate areas showed strong positive associations with individual differences in motor reactivity but negative associations with autonomic reactivity. Notably, individual differences in OFC activation was almost fully accounted by the combination of individual measures of autonomic and motor reactivity (R(2)=0.93). Additionally, trial-to-trial fluctuations of RIII-reflex and SCR (within-subjects) were proportional to shock-evoked responses in subgenual cingulate cortex (RIII), anterior insula (SCR) and midcingulate cortex (SCR and RIII). Together, these results confirm that individual differences in perceptual, motor, and autonomic components of pain reflect robust individual differences in brain activity. Furthermore, the brain correlates of trial-to-trial fluctuations in pain responses provide additional evidence for a partial segregation of sub-systems involved more specifically in the ongoing monitoring, and possibly the regulation, of pain-related motor and autonomic responses.
Tai, Bruce L; Zhang, Lihui; Wang, Anthony C; Sullivan, Stephen; Wang, Guangjun; Shih, Albert J
This research explores the feasibility of using motor electrical feedback to estimate temperature rise during a surgical bone grinding procedure. High-speed bone grinding is often used during skull base neurosurgery to remove cranial bone and approach skull base tumors through the nasal corridor. Grinding-induced heat could propagate and potentially injure surrounding nerves and arteries, and therefore, predicting the temperature in the grinding region would benefit neurosurgeons during the operation. High-speed electric motors are controlled by pulse-width-modulation (PWM) to alter the current input and thus maintain the rotational speed. Assuming full mechanical to thermal power conversion in the grinding process, PWM can be used as feedback for heat generation and temperature prediction. In this study, the conversion model was established from experiments under a variety of grinding conditions and an inverse heat transfer method to determine heat flux. Given a constant rotational speed, the heat conversion was represented by a linear function, and could predict temperature from the experimental data with less than 20% errors. Such results support the advance of this technology for practical application.
Sherrill, Delsey M; Moy, Marilyn L; Reilly, John J; Bonato, Paolo
Background Advances in miniature sensor technology have led to the development of wearable systems that allow one to monitor motor activities in the field. A variety of classifiers have been proposed in the past, but little has been done toward developing systematic approaches to assess the feasibility of discriminating the motor tasks of interest and to guide the choice of the classifier architecture. Methods A technique is introduced to address this problem according to a hierarchical framework and its use is demonstrated for the application of detecting motor activities in patients with chronic obstructive pulmonary disease (COPD) undergoing pulmonary rehabilitation. Accelerometers were used to collect data for 10 different classes of activity. Features were extracted to capture essential properties of the data set and reduce the dimensionality of the problem at hand. Cluster measures were utilized to find natural groupings in the data set and then construct a hierarchy of the relationships between clusters to guide the process of merging clusters that are too similar to distinguish reliably. It provides a means to assess whether the benefits of merging for performance of a classifier outweigh the loss of resolution incurred through merging. Results Analysis of the COPD data set demonstrated that motor tasks related to ambulation can be reliably discriminated from tasks performed in a seated position with the legs in motion or stationary using two features derived from one accelerometer. Classifying motor tasks within the category of activities related to ambulation requires more advanced techniques. While in certain cases all the tasks could be accurately classified, in others merging clusters associated with different motor tasks was necessary. When merging clusters, it was found that the proposed method could lead to more than 12% improvement in classifier accuracy while retaining resolution of 4 tasks. Conclusion Hierarchical clustering methods are relevant
Activating Cell Death Ligand Signaling Through Proteasome Inhibition PRINCIPAL INVESTIGATOR: Steven R Schwarze...SUBTITLE Activating Cell Death Ligand Signaling Through 5a. CONTRACT NUMBER Proteasome Inhibition 5b. GRANT NUMBER W81XWH-08-1-0392 5c...proteasome inhibition can act as an anti-neoplastic agent in vivo by sensitizing cancer cells to cell death ligands in the tumor microenvironment
Pasquereau, Benjamin; DeLong, Mahlon R.
Abnormalities in the movement-related activation of the primary motor cortex (M1) are thought to be a major contributor to the motor signs of Parkinson’s disease. The existing evidence, however, variably indicates that M1 is under-activated with movement, overactivated (due to a loss of functional specificity) or activated with abnormal timing. In addition, few models consider the possibility that distinct cortical neuron subtypes may be affected differently. Those gaps in knowledge were addressed by studying the extracellular activity of antidromically-identified lamina 5b pyramidal-tract type neurons (n = 153) and intratelencephalic-type corticostriatal neurons (n = 126) in the M1 of two monkeys as they performed a step-tracking arm movement task. We compared movement-related discharge before and after the induction of parkinsonism by administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and quantified the spike rate encoding of specific kinematic parameters of movement using a generalized linear model. The fraction of M1 neurons with movement-related activity declined following MPTP but only marginally. The strength of neuronal encoding of parameters of movement was reduced markedly (mean 29% reduction in the coefficients from the generalized linear model). This relative decoupling of M1 activity from kinematics was attributable to reductions in the coefficients that estimated the spike rate encoding of movement direction (−22%), speed (−40%), acceleration (−49%) and hand position (−33%). After controlling for MPTP-induced changes in motor performance, M1 activity related to movement itself was reduced markedly (mean 36% hypoactivation). This reduced activation was strong in pyramidal tract-type neurons (−50%) but essentially absent in corticostriatal neurons. The timing of M1 activation was also abnormal, with earlier onset times, prolonged response durations, and a 43% reduction in the prevalence of movement-related changes
BACKGROUND: Pyrethroids are neurotoxic insecticides used in a variety of indoor and outdoor applications. Previous research characterized the acute dose-effect functions for 11 pyrethroids administered orally in corn oil (1 mL/kg) based on assessment of motor activity. OBJECTIVES...
Ulyaninskiy, L. S.; Urmancheyeva, T. G.; Stepanyan, Y. P.; Fufacheva, A. A.; Gritsak, A. V.; Kuznetsova, B. A.; Kvitka, A. A.
Experimental emotional stress which can produce various disorders of cardiac rhythm: sinus tachycardia, atrial fibrillation, ventricular, extrasystoles and paroxysmal ventricular tachysystoles was studied. In these conditions the adrenalin content in the blood and myocardium is increased 3 to 4 times. It is found that moderate motor activity leads to a relative decrease of adrenalin in the myocardium and arrest of cardiac arrhythmias.
Mitchell, J D; Jackson, M J; Pentland, B
Indices of free-radical activity and lipid peroxidation were studied in cerebrospinal fluid samples obtained from 11 patients with motor neuron disease and 11 reference subjects. No differences were found between the two groups. The significance of this finding is discussed in relation to current views of the possible pathogenesis of this disease. PMID:3625217
Bhatia, Punum; Davis, Alan; Shamas-Brandt, Ellen
Research Findings: A quasi-experiment was undertaken to test the effect of Montessori practical life activities on kindergarten children's fine motor development and hand dominance over an 8-month period. Participants were 50 children age 5 in 4 Montessori schools and 50 students age 5 in a kindergarten program in a high-performing suburban…
The USEPA Developmental Neurotoxicity (DNT) Study Test Guideline (OPPTS 870.6300) calls for a battery of functional and neuropathological assessments in offspring during and following maternal exposure. The battery includes measurement of motor activity on post-natal days (PND) ...
Maldonado, C; Rodriíuez-Arias, M; Aguilar, M A; Miñarro, J
There are several reports suggesting that gamma-hydroxybutyric acid (GHB) influences the endogenous opioid system. The present study aimed to investigate the effects of GHB on motor and social activities and to examine its influence on morphine's actions on these behaviours. In a first experiment, several doses of GHB were studied but only the highest (200 and 400 mg/kg) produced a decrease in spontaneous motor activity measured in an actimeter cage. When hyperactivity induced by injecting 50 mg/kg of morphine was evaluated, all the GHB doses efficiently counteracted this morphine action. Using the paradigm of isolation-induced aggression, administration of 200 mg/kg of GHB significantly decreased threat and attack without impairing motor activity and, in addition, increased time spent in social contact. GHB increased morphine's suppression of threat or nonsocial exploratory behaviours. In conclusion, the interaction between GHB and the opioid systems was confirmed, with the drug having an additive effect on morphine-affected social behaviours but counteracting morphine-induced increases in motor activity.
Neurobehavioral evaluations are emerging as a key component in neurotoxicity testing. The tests most often used for screening are the functional observational battery (FOB) and motor activity. The FOB is a series of non-invasive observational and manipulative measures which ass...
Motor activity was examined in adult female Long-Evans rats in a photocell device during daily (M-F) 30-min sessions. Following adaptation to the testing routine the rats were divided into six groups of eight that were designated to receive either nothing (non-injected control),...
Lee, Dong; Byun, Kyung-Eun; Choi, Dong; Kim, Eunji; Kim, Daesan; Seo, David; Yang, Heejun; Seo, Sunae; Hong, Seunghun; Hybrid Nanodevice Lab Team; Samsung Research Park Team
Biological motors have been drawing an attention as a key component for highly efficient nanomechanical systems. For such applications, many researchers have tried to control the activity of motor proteins through various methods such as microfluidics or UV-active compounds. However, these methods have some limitations such as the incapability of controlling local biomotor activity and a slow response rate. Herein, we developed a graphene-polymer hybrid nanostructure-based bioenergy storage device which enables the real-time control of biomotor activity. In this strategy, graphene layers functionalized with amine groups were utilized as a transparent electrode supporting the motility of biomotors. And conducting polymer patterns doped with adenosine triphosphate (ATP) were electrically deposited on the graphene and utilized for the fast release of ATP by electrical stimuli through the graphene. Such controlled release of ATP allowed us to control the motility of actin filaments propelled by myosin biomotors in real time. This strategy should enable integrated nanodevices for the real-time control of biological motors to the nanodevices, which can be a significant stepping stone toward hybrid nanomechanical systems based on motor proteins.
These studies grew out of an unexpected finding from investigations of the neurobehavioral toxicity of PCBs. This paper shows that episodic, or recurring intermittent acute exposures to nicotine produce dramatic and long-lasting changes in the motor activity of laboratory rats. ...
Vasquez, Claudia G; Heissler, Sarah M; Billington, Neil; Sellers, James R; Martin, Adam C
Non-muscle cell contractility is critical for tissues to adopt shape changes. Although, the non-muscle myosin II holoenzyme (myosin) is a molecular motor that powers contraction of actin cytoskeleton networks, recent studies have questioned the importance of myosin motor activity cell and tissue shape changes. Here, combining the biochemical analysis of enzymatic and motile properties for purified myosin mutants with in vivo measurements of apical constriction for the same mutants, we show that in vivo constriction rate scales with myosin motor activity. We show that so-called phosphomimetic mutants of the Drosophila regulatory light chain (RLC) do not mimic the phosphorylated RLC state in vitro. The defect in the myosin motor activity in these mutants is evident in developing Drosophila embryos where tissue recoil following laser ablation is decreased compared to wild-type tissue. Overall, our data highlights that myosin activity is required for rapid cell contraction and tissue folding in developing Drosophila embryos. DOI: http://dx.doi.org/10.7554/eLife.20828.001 PMID:28035903
Saig, Avraham; Gordon, Goren; Assa, Eldad; Arieli, Amos; Ahissar, Ehud
Perception involves motor control of sensory organs. However, the dynamics underlying emergence of perception from motor-sensory interactions are not yet known. Two extreme possibilities are as follows: (1) motor and sensory signals interact within an open-loop scheme in which motor signals determine sensory sampling but are not affected by sensory processing and (2) motor and sensory signals are affected by each other within a closed-loop scheme. We studied the scheme of motor-sensory interactions in humans using a novel object localization task that enabled monitoring the relevant overt motor and sensory variables. We found that motor variables were dynamically controlled within each perceptual trial, such that they gradually converged to steady values. Training on this task resulted in improvement in perceptual acuity, which was achieved solely by changes in motor variables, without any change in the acuity of sensory readout. The within-trial dynamics is captured by a hierarchical closed-loop model in which lower loops actively maintain constant sensory coding, and higher loops maintain constant sensory update flow. These findings demonstrate interchangeability of motor and sensory variables in perception, motor convergence during perception, and a consistent hierarchical closed-loop perceptual model.
Jahnke, Sven; Memmesheimer, Raoul-Martin; Timme, Marc
A wide range of networked systems exhibit highly connected nodes (hubs) as prominent structural elements. The functional roles of hubs in the collective nonlinear dynamics of many such networks, however, are not well understood. Here, we propose that hubs in neural circuits may activate local signal transmission along sequences of specific subnetworks. Intriguingly, in contrast to previous suggestions of the functional roles of hubs, here, not the hubs themselves, but nonhub subnetworks transfer the signals. The core mechanism relies on hubs and nonhubs providing activating feedback to each other. It may, thus, induce the propagation of specific pulse and rate signals in neuronal and other communication networks.
Olshansky, Michael P; Bar, Rachel J; Fogarty, Mary; DeSouza, Joseph F X
The current study used functional magnetic resonance imaging to examine the neural activity of an expert dancer with 35 years of break-dancing experience during the kinesthetic motor imagery (KMI) of dance accompanied by highly familiar and unfamiliar music. The goal of this study was to examine the effect of musical familiarity on neural activity underlying KMI within a highly experienced dancer. In order to investigate this in both primary sensory and motor planning cortical areas, we examined the effects of music familiarity on the primary auditory cortex [Heschl's gyrus (HG)] and the supplementary motor area (SMA). Our findings reveal reduced HG activity and greater SMA activity during imagined dance to familiar music compared to unfamiliar music. We propose that one's internal representations of dance moves are influenced by auditory stimuli and may be specific to a dance style and the music accompanying it.
Ahabrach, Hanan; Piedrafita, Blanca; Ayad, Abdelmalik; El Mlili, Nisrin; Errami, Mohammed; Felipo, Vicente; Llansola, Marta
Patients with liver cirrhosis may present hepatic encephalopathy with a wide range of neurological disturbances and alterations in sleep quality and in the sleep-wake circadian rhythm. Hyperammonemia is a main contributor to the neurological alterations in hepatic encephalopathy. We have assessed, in an animal model of chronic hyperammonemia without liver failure, the effects of hyperammonemia per se on the circadian rhythms of motor activity, temperature, and plasma levels of adrenal corticosteroid hormones. Chronic hyperammonemia alters the circadian rhythms of locomotor activity and of cortisol and corticosterone levels in blood. Different types of motor activity are affected differentially. Hyperammonemia significantly alters the rhythm of spontaneous ambulatory activity, reducing strongly ambulatory counts and slightly average velocity during the night (the active phase) but not during the day, resulting in altered circadian rhythms. In contrast, hyperammonemia did not affect wheel running at all, indicating that it affects spontaneous but not voluntary activity. Vertical activity was affected only very slightly, indicating that hyperammonemia does not induce anxiety. Hyperammonemia abolished completely the circadian rhythm of corticosteroid hormones in plasma, completely eliminating the peaks of cortisol and corticosterone present in control rats at the start of the dark period. The data reported show that chronic hyperammonemia, similar to that present in patients with liver cirrhosis, alters the circadian rhythms of corticosteroid hormones and of motor activity. This suggests that hyperammonemia would be a relevant contributor to the alterations in corticosteroid hormones and in circadian rhythms in patients with liver cirrhosis.
Jena, D. P.; Panigrahi, S. N.
Perturbations in the drawn current due to the fluctuation in load on the blade during the processing of food in a food processor has been used to design an operator assistance system. A robust signal processing scheme has been proposed in order to analyze the extremely feeble current fluctuations in the motor controller circuit. An enveloping technique followed by a wavelet based denoising filter has been proposed for extracting useful information from the acquired current signal. Output of this scheme is fed into an intelligent decision making algorithm, which primarily is able to take two kinds of decisions, finally assists the user in making certain informed judgments. One of these decisions deals with the completion of the mixing or grinding operation whereas the other deals with cautioning the user about the presence of undesirable impurities in the substance being processed. Effectiveness of the developed method has been demonstrated, first on an appropriately formulated simulation, and then on the acquired signal from the experimental setup.
Chadderdon, George L.; Mohan, Ashutosh; Suter, Benjamin A.; Neymotin, Samuel A.; Kerr, Cliff C.; Francis, Joseph T.; Shepherd, Gordon M. G.; Lytton, William W.
The deceptively simple laminar structure of neocortex belies the complexity of intra- and interlaminar connectivity. We developed a computational model based primarily on a unified set of brain activity mapping studies of mouse M1. The simulation consisted of 775 spiking neurons of 10 cell types with detailed population-to-population connectivity. Static analysis of connectivity with graph-theoretic tools revealed that the corticostriatal population showed strong centrality, suggesting that would provide a network hub. Subsequent dynamical analysis confirmed this observation, in addition to revealing network dynamics that cannot be readily predicted through analysis of the wiring diagram alone. Activation thresholds depended on the stimulated layer. Low stimulation produced transient activation, while stronger activation produced sustained oscillations where the threshold for sustained responses varied by layer: 13% in layer 2/3, 54% in layer 5A, 25% in layer 5B, and 17% in layer 6. The frequency and phase of the resulting oscillation also depended on stimulation layer. By demonstrating the effectiveness of combined static and dynamic analysis, our results show how static brain maps can be related to the results of brain activity mapping. PMID:24708371
Cendelín, Jan; Korelusová, Ivana; Vozeh, Frantisek
Lurcher mutant mice represent a model of olivocerebellar degeneration. They are used to investigate cerebellar functions, consequences of cerebellar degeneration and methods of therapy influencing them. The aim of the work was to assess the effect of foetal cerebellar graft transplantation, repeated enforced physical activity and the combination of both these types of treatment on motor skills, spontaneous motor activity and spatial learning ability in adult B6CBA Lurcher mice. Foetal cerebellar grafts were applied into the cerebellum of Lurchers in the form of solid tissue pieces. Enforced motor activity was realised through rotarod training. Motor functions were examined using bar, ladder and rotarod tests. Spatial learning was tested in the Morris water maze. Spontaneous motor activity in the open field was observed. The presence of the graft was examined histologically. Enforced physical activity led to moderate improvement of some motor skills and to a significant amelioration of spatial learning ability in Lurchers. The transplantation of cerebellar tissue did not influence motor functions significantly but led to an improvement of spatial learning ability. Mutual advancement of the effects of both types of treatment was not observed. Spontaneous motor activity was influenced neither by physical activity nor by the transplantation. Physical activity did not influence the graft survival and development. Because nerve sprouting and cell migration from the graft to the host cerebellum was poor, the functional effects of the graft should be explained with regard to its trophic influence rather than with any involvement of the grafted cells into neural circuitries.
Oakley, Fredrick D.; Abbott, Duane; Li, Qiang
Abstract Subcellular compartmentalization of reactive oxygen species (ROS) plays a critical role in transmitting cell signals in response to environmental stimuli. In this regard, signals at the plasma membrane have been shown to trigger NADPH oxidase-dependent ROS production within the endosomal compartment and this step can be required for redox-dependent signal transduction. Unique features of redox-active signaling endosomes can include NADPH oxidase complex components (Nox1, Noxo1, Noxa1, Nox2, p47phox, p67phox, and/or Rac1), ROS processing enzymes (SOD1 and/or peroxiredoxins), chloride channels capable of mediating superoxide transport and/or membrane gradients required for Nox activity, and novel redox-dependent sensors that control Nox activity. This review will discuss the cytokine and growth factor receptors that likely mediate signaling through redox-active endosomes, and the common mechanisms whereby they act. Additionally, the review will cover ligand-independent environmental injuries, such as hypoxia/reoxygenation injury, that also appear to facilitate cell signaling through NADPH oxidase at the level of the endosome. We suggest that redox-active endosomes encompass a subset of signaling endosomes that we have termed redoxosomes. Redoxosomes are uniquely equipped with redox-processing proteins capable of transmitting ROS signals from the endosome interior to redox-sensitive effectors on the endosomal surface. In this manner, redoxosomes can control redox-dependent effector functions through the spatial and temporal regulation of ROS as second messengers. Antioxid. Redox Signal. 11, 1313–1333. PMID:19072143
Vallesi, Antonino; McIntosh, Anthony R; Kovacevic, Natasa; Chan, Sam C C; Stuss, Donald T
Functional hemispheric asymmetry can be lost with aging. In this electroencephalographic study, we assessed hemispheric asymmetries in regulating motor responses by analyzing oscillatory brain activity during a go/nogo task in younger and older right-handed participants. Three conditions were embedded in the task: go, high-conflict and low-conflict nogo. The hand used to respond to go stimuli was varied block-wise. Independently of the go/nogo conditions and responding hand, young participants showed asymmetric desynchronizations in the mu (10 Hz) and beta (18-22 Hz) frequency bands that was stronger in the scalp sensorimotor region contralateral to the hand used for the go responses, while older adults showed a more symmetric pattern of desynchronization. These findings indicate that a loss of hemispheric asymmetry is a hallmark of the aging motor system, consistent with a decline of inter-hemispheric motor inhibition in normal aging.
Matsukawa, Kanji; Ishii, Kei; Idesako, Mitsuhiro; Ishida, Tomoko; Endo, Kana; Liang, Nan
Our laboratory has recently demonstrated that central command provides selective inhibition of the cardiomotor component of aortic (AOR) baroreflex during exercise, preserving carotid sinus (CS) baroreflex. To further explore the differential effects of central command on the arterial baroreflexes, we surgically separated the AOR and CS baroreflex systems, to identify the input-output relationship of each baroreflex system using brief occlusion of the abdominal aorta in decerebrate cats. Baroreflex sensitivity for heart rate (HR) was estimated from the baroreflex ratio between the pressor and bradycardia responses during aortic occlusion and from the slope of the baroreflex curve between the changes in mean arterial blood pressure (ΔMAP) and ΔHR. Spontaneous motor activity accompanied the abrupt increases in HR and MAP. When aortic occlusion was given at the onset of spontaneous motor activity, the baroreflex ratio was blunted to 11-25% of the preexercise value in either intact or AOR baroreflex. The slope of the ΔMAP-ΔHR curve was similarly attenuated at the onset of spontaneous motor activity to 11-18% of the slope during the preexercise period. In contrast, in the CS baroreflex, the baroreflex ratio and curve slope were not significantly (P>0.05) altered by spontaneous motor activity. An upward shift of the baroreflex curve appeared at the onset of spontaneous motor activity, irrespective of the intact, AOR, and CS baroreflex conditions. Taken together, it is concluded that central command provides selective inhibition for the cardiomotor limb of the aortic baroreflex at the onset of exercise, which in turn contributes to an instantaneous increase in HR.
Jacquet, Pierre O; Roy, Alice C; Chambon, Valérian; Borghi, Anna M; Salemme, Roméo; Farnè, Alessandro; Reilly, Karen T
Predicting intentions from observing another agent's behaviours is often thought to depend on motor resonance - i.e., the motor system's response to a perceived movement by the activation of its stored motor counterpart, but observers might also rely on prior expectations, especially when actions take place in perceptually uncertain situations. Here we assessed motor resonance during an action prediction task using transcranial magnetic stimulation to probe corticospinal excitability (CSE) and report that experimentally-induced updates in observers' prior expectations modulate CSE when predictions are made under situations of perceptual uncertainty. We show that prior expectations are updated on the basis of both biomechanical and probabilistic prior information and that the magnitude of the CSE modulation observed across participants is explained by the magnitude of change in their prior expectations. These findings provide the first evidence that when observers predict others' intentions, motor resonance mechanisms adapt to changes in their prior expectations. We propose that this adaptive adjustment might reflect a regulatory control mechanism that shares some similarities with that observed during action selection. Such a mechanism could help arbitrate the competition between biomechanical and probabilistic prior information when appropriate for prediction.
Jacquet, Pierre O.; Roy, Alice C.; Chambon, Valérian; Borghi, Anna M.; Salemme, Roméo; Farnè, Alessandro; Reilly, Karen T.
Predicting intentions from observing another agent’s behaviours is often thought to depend on motor resonance – i.e., the motor system’s response to a perceived movement by the activation of its stored motor counterpart, but observers might also rely on prior expectations, especially when actions take place in perceptually uncertain situations. Here we assessed motor resonance during an action prediction task using transcranial magnetic stimulation to probe corticospinal excitability (CSE) and report that experimentally-induced updates in observers’ prior expectations modulate CSE when predictions are made under situations of perceptual uncertainty. We show that prior expectations are updated on the basis of both biomechanical and probabilistic prior information and that the magnitude of the CSE modulation observed across participants is explained by the magnitude of change in their prior expectations. These findings provide the first evidence that when observers predict others’ intentions, motor resonance mechanisms adapt to changes in their prior expectations. We propose that this adaptive adjustment might reflect a regulatory control mechanism that shares some similarities with that observed during action selection. Such a mechanism could help arbitrate the competition between biomechanical and probabilistic prior information when appropriate for prediction. PMID:27243157
Canu, M H; Darnaudéry, M; Falempin, M; Maccari, S; Viltart, O
Environmental changes that occur in daily life or, in particular, in situations like actual or simulated microgravity require neuronal adaptation of sensory and motor functions. Such conditions can exert long-lasting disturbances on an individual's adaptive ability. Additionally, prenatal stress also leads to behavioral and physiological abnormalities in adulthood. Therefore, the aims of the present study were (a) to evaluate in adult rats the behavioral motor adaptation that follows 14 days of exposure to simulated microgravity (hindlimb unloading) and (b) to determine whether restraint prenatal stress influences this motor adaptation. For this purpose, the authors assessed rats' motor reactivity to novelty, their skilled walking on a ladder, and their swimming performance. Results showed that unloading severely impaired motor activity and skilled walking. By contrast, it had no effect on swimming performance. Moreover, results demonstrated for the first time that restraint prenatal stress exacerbates the effects of unloading. These results are consistent with the role of a steady prenatal environment in allowing an adequate development and maturation of sensorimotor systems to generate adapted responses to environmental challenges during adulthood.
De Vico Fallani, F; Astolfi, L; Cincotti, F; Mattia, D; Maglione, A G; Vecchiato, G; Toppi, J; Della Penna, F; Salinari, S; Babiloni, F; Zouridakis, G
The evaluation of the topological properties of brain networks is an emergent research topic, since the estimated cerebral connectivity patterns often have relatively large size and complex structure. Since a graph is a mathematical representation of a network, the use of a theoretical graph approach would describe concisely the topological features of the functional brain connectivity network estimated using neuroimaging techniques. In the present study, we analyze the changes in brain synchronization networks using high-resolution EEG signals obtained during performance of a complex goal-directed visuomotor task. Our results show that the cortical network is more stable when subjects reach the goal than when they fail by hitting an obstacle. These findings suggest the presence of a possible cerebral "marker" for motor actions that result in successful reaching of a target.
Criteria)( Stremler 129). The analog signal (P) was first applied to a precision analog low-pass filter with a cut-off frequency of approximately 2900...is the application of the Hilbert Transform. 2.1 The Hilbert Transform If s(t) is a real signal, then the Hilbert transform( Stremler 260) is defined...as the convolution of s (t) by (lhcr*t): 2.1 S h(t)S(t) ( mf’so.). -dX After taking the Fourier Transform( Stremler 84) Of Sh(t), and shifting to the
Skidmore, F M; Yang, M; Baxter, L; von Deneen, K; Collingwood, J; He, G; Tandon, R; Korenkevych, D; Savenkov, A; Heilman, K M; Gold, M; Liu, Y
Apathy and depression are heterogeneous syndromes with symptoms that overlap clinically. This clinical overlap leads to problems with classification and diagnosis in clinical populations. No functional imaging study has attempted to separate brain regions altered in apathy from those altered in depression in a clinical population. Parkinson disease (PD) is a disorder in which apathy and depression co-exist in a single population. We evaluate the relationship between apathy, depression, and motor severity of disease in PD, focusing on the relationship between these factors and the amplitude of the low frequency fluctuation (ALFF) in the resting state. We first evaluated if the resting ALFF signal is a reliable measure for our clinical question. For this, we develop and introduce a cross validation approach we term the "Regional Mapping of Reliable Differences" (RMRD) method to evaluate reliability of regions of interest deemed "significant" by standard voxel-wise techniques. Using this approach, we show that the apathy score in this sample is best predicted by ALFF signal in the left supplementary motor cortex, the right orbitofrontal cortex, and the right middle frontal cortex, whereas depression score is best predicted by ALFF signal in the right subgenual cingulate. Disease severity was best predicted by ALFF signal in the right putamen. A number of additional regions are also statistically (but not reliably) correlated with our neuropsychological measures and disease severity. Our results support the use of resting fMRI as a means to evaluate neuropsychiatric states and motor disease progression in Parkinson disease, and the clinical and epidemiologic observation that apathy and depression are distinct pathological entities. Our finding that "significance" and "reliability" are dissociated properties of regions of interest identified as significant using standard voxel-wise techniques suggests that including reliability analyses may add useful scientific
Albouy, Geneviève; King, Bradley R.; Schmidt, Christina; Desseilles, Martin; Dang-Vu, Thien Thanh; Balteau, Evelyne; Phillips, Christophe; Degueldre, Christian; Orban, Pierre; Benali, Habib; Peigneux, Philippe; Luxen, André; Karni, Avi; Doyon, Julien; Maquet, Pierre; Korman, Maria
Motor memory consolidation is characterized, in part, by a sleep-facilitated decrease in susceptibility to subsequent interfering experiences. Surprisingly, the cerebral substrates supporting this phenomenon have never been examined. We used fMRI to investigate the neural correlates of the influence of sleep on interference to motor memory consolidation. Healthy young adults were trained on a sequential motor task, and subsequently practiced a second competing sequence after an interval including diurnal sleep or wakefulness. Participants were then retested on the initial sequence 8 h and 24 h (including nocturnal sleep) after training. Results demonstrated that a post-training nap significantly protected memory against interference at 8 h and modulated the link between cerebral activity and behavior, such that a smaller post-interference decrease in cortico-striatal activity was associated with better performance. Interestingly, the protective effect of a nap was only transitory, as both groups performed similarly at 24 h. Activity in cortico-striatal areas that was disrupted during the day, presumably due to interference and accentuated in the absence of a nap, was restored overnight. Altogether, our findings offer the first evidence that cortico-striatal areas play a critical role in the transient sleep-facilitated reduction in motor memory vulnerability and in the overnight restoration of previously degraded memories. PMID:27725727
Albouy, Geneviève; King, Bradley R; Schmidt, Christina; Desseilles, Martin; Dang-Vu, Thien Thanh; Balteau, Evelyne; Phillips, Christophe; Degueldre, Christian; Orban, Pierre; Benali, Habib; Peigneux, Philippe; Luxen, André; Karni, Avi; Doyon, Julien; Maquet, Pierre; Korman, Maria
Motor memory consolidation is characterized, in part, by a sleep-facilitated decrease in susceptibility to subsequent interfering experiences. Surprisingly, the cerebral substrates supporting this phenomenon have never been examined. We used fMRI to investigate the neural correlates of the influence of sleep on interference to motor memory consolidation. Healthy young adults were trained on a sequential motor task, and subsequently practiced a second competing sequence after an interval including diurnal sleep or wakefulness. Participants were then retested on the initial sequence 8 h and 24 h (including nocturnal sleep) after training. Results demonstrated that a post-training nap significantly protected memory against interference at 8 h and modulated the link between cerebral activity and behavior, such that a smaller post-interference decrease in cortico-striatal activity was associated with better performance. Interestingly, the protective effect of a nap was only transitory, as both groups performed similarly at 24 h. Activity in cortico-striatal areas that was disrupted during the day, presumably due to interference and accentuated in the absence of a nap, was restored overnight. Altogether, our findings offer the first evidence that cortico-striatal areas play a critical role in the transient sleep-facilitated reduction in motor memory vulnerability and in the overnight restoration of previously degraded memories.
Lawhern, Vernon; Wu, Wei; Hatsopoulos, Nicholas; Paninski, Liam
Generalized linear models (GLMs) have been developed for modeling and decoding population neuronal spiking activity in the motor cortex. These models provide reasonable characterizations between neural activity and motor behavior. However, they lack a description of movement-related terms which are not observed directly in these experiments, such as muscular activation, the subject's level of attention, and other internal or external states. Here we propose to include a multi-dimensional hidden state to address these states in a GLM framework where the spike count at each time is described as a function of the hand state (position, velocity, and acceleration), truncated spike history, and the hidden state. The model can be identified by an Expectation-Maximization algorithm. We tested this new method in two datasets where spikes were simultaneously recorded using a multi-electrode array in the primary motor cortex of two monkeys. It was found that this method significantly improves the model-fitting over the classical GLM, for hidden dimensions varying from 1 to 4. This method also provides more accurate decoding of hand state (reducing the mean square error by up to 29% in some cases), while retaining real-time computational efficiency. These improvements on representation and decoding over the classical GLM model suggest that this new approach could contribute as a useful tool to motor cortical decoding and prosthetic applications.
Nikitin, A S; Abzalov, R A; Abzalov, N I; Vafina, E Z
The indicators of heart pumping ability of rats at a muscular loading of the maximum power and also in the conditions of transition from sharply strengthened motor activity regime on a strengthened motor activity regime at adrenergic influence stimulation and blockade were investigated. At rats of 100-daily age at the strengthened motor activity heart rate is less, and blood stroke volume is more, than in the rats, subject to muscular loading of the maximum power. The adrenergic influence on the heart's pumping ability of sharply strengthened motor activity rats is much more, than of unlimited motor activity rats. At the α1-adrenoreceptors blockade at 100-daily rats the decreasing in intensity of muscular loading causes increased in adrenergic influence on heart pumping ability.
Qiu, Shuang; Xiao, Chengfeng; Robertson, R. Meldrum
There is considerable interest in the therapeutic benefits of long-term sensory stimulation for improving cognitive abilities and motor performance of stroke patients. The rationale is that such stimulation would activate mechanisms of neural plasticity to promote enhanced coordination and associated circuit functions. Experimental approaches to characterize such mechanisms are needed. Drosophila melanogaster is one of the most attractive model organisms to investigate neural mechanisms responsible for stimulation-induced behaviors with its powerful accessibility to genetic analysis. In this study, the effect of chronic sensory stimulation (pulsed light stimulation) on motor activity in w1118 flies was investigated. Flies were exposed to a chronic pulsed light stimulation protocol prior to testing their performance in a standard locomotion assay. Flies responded to pulsed light stimulation with increased boundary preference and travel distance in a circular arena. In addition, pulsed light stimulation increased the power of extracellular electrical activity, leading to the enhancement of periodic electrical activity which was associated with a centrally-generated motor pattern (struggling behavior). In contrast, such periodic events were largely missing in w1118 flies without pulsed light treatment. These data suggest that the sensory stimulation induced a response in motor activity associated with the modifications of electrical activity in the central nervous system (CNS). Finally, without pulsed light treatment, the wild-type genetic background was associated with the occurrence of the periodic activity in wild-type Canton S (CS) flies, and w+ modulated the consistency of periodicity. We conclude that pulsed light stimulation modifies behavioral and electrophysiological activities in w1118 flies. These data provide a foundation for future research on the genetic mechanisms of neural plasticity underlying such behavioral modification. PMID:27684063
Delaville, Claire; McCoy, Alex J; Gerber, Colin M; Cruz, Ana V; Walters, Judith R
Oscillatory activity in both beta and gamma ranges has been recorded in the subthalamic nucleus (STN) of Parkinson's disease (PD) patients and linked to motor function, with beta activity considered antikinetic, and gamma activity, prokinetic. However, the extent to which nonmotor networks contribute to this activity is unclear. This study uses hemiparkinsonian rats performing a treadmill walking task to compare synchronized STN local field potential (LFP) activity with activity in motor cortex (MCx) and medial prefrontal cortex (mPFC), areas involved in motor and cognitive processes, respectively. Data show increases in STN and MCx 29-36 Hz LFP spectral power and coherence after dopamine depletion, which are reduced by apomorphine and levodopa treatments. In contrast, recordings from mPFC 3 weeks after dopamine depletion failed to show peaks in 29-36 Hz LFP power. However, mPFC and STN both showed peaks in the 45-55 Hz frequency range in LFP power and coherence during walking before and 21 days after dopamine depletion. Interestingly, power in this low gamma range was transiently reduced in both mPFC and STN after dopamine depletion but recovered by day 21. In contrast to the 45-55 Hz activity, the amplitude of the exaggerated 29-36 Hz rhythm in the STN was modulated by paw movement. Furthermore, as in PD patients, after dopamine treatment a third band (high gamma) emerged in the lesioned hemisphere. The results suggest that STN integrates activity from both motor and cognitive networks in a manner that varies with frequency, behavioral state, and the integrity of the dopamine system.
Mrongovius, R I; Ghosh, P; Bolt, A G
1. A series of 1-benzylcycloalkylamines with cycloalkyl rings of five, six or seven carbons and with various benzyl ring substituents (3-Cl, 4-Cl, 4-F, 3-CF3) was prepared and tested for anorectic and motor activity effects in rats. 2. Two potent, non-stimulant, anorectics were found: 1-(3-chlorobenzyl)-cycloheptylamine, and its N-methyl analogue. The activity of these compounds resembled that of chlorphentermine.
Martin, J H; Donarummo, L; Hacking, A
This study examined the effects of blocking neural activity in sensory motor cortex during early postnatal development on prehension. We infused muscimol, either unilaterally or bilaterally, into the sensory motor cortex of cats to block activity continuously between postnatal weeks 3-7. After stopping infusion, we trained animals to reach and grasp a cube of meat and tested behavior thereafter. Animals that had not received muscimol infusion (unilateral saline infusion; age-matched) reached for the meat accurately with small end-point errors. They grasped the meat using coordinated digit flexion followed by forearm supination on 82.7% of trials. Performance using either limb did not differ significantly. In animals receiving unilateral muscimol infusion, reaching and grasping using the limb ipsilateral to the infusion were similar to controls. The limb contralateral to infusion showed significant increases in systematic and variable reaching end-point errors, often requiring subsequent corrective movements to contact the meat. Grasping occurred on only 14.8% of trials, replaced on most trials by raking without distal movements. Compensatory adjustments in reach length and angle, to maintain end-point accuracy as movements were started from a more lateral position, were less effective using the contralateral limb than ipsilateral limb. With bilateral inactivations, the form of reaching and grasping impairments was identical to that produced by unilateral inactivation, but the magnitude of the reaching impairments was less. We discuss these results in terms of the differential effects of unilateral and bilateral inactivation on corticospinal tract development. We also investigated the degree to which these prehension impairments after unilateral blockade reflect control by each hemisphere. In animals that had received unilateral blockade between postnatal weeks (PWs) 3 and 7, we silenced on-going activity (after PW 11) during task performance using continuous
Kabir, Muammar M; Beig, Mirza I; Baumert, Mathias; Trombini, Mimosa; Mastorci, Francesca; Sgoifo, Andrea; Walker, Frederick R; Day, Trevor A; Nalivaiko, Eugene
Our aim was to assess the impact of motor activity and of arousing stimuli on respiratory rate in the awake rats. The study was performed in male adult Sprague-Dawley (SD, n=5) and Hooded Wistar (HW, n=5) rats instrumented for ECG telemetry. Respiratory rate was recorded using whole-body plethysmograph, with a piezoelectric sensor attached for the simultaneous assessment of motor activity. All motor activity was found to be associated with an immediate increase in respiratory rate that remained elevated for the whole duration of movement; this was reflected by: i) bimodal distribution of respiratory intervals (modes for slow peak: 336+/-19 and 532+/-80 ms for HW and SD, p<0.05; modes for fast peak 128+/-6 and 132+/-7 ms for HW and SD, NS); and ii) a tight correlation between total movement time and total time of tachypnoea, with an R(2) ranging 0.96-0.99 (n=10, p<0001). The extent of motor-related tachypnoea was significantly correlated with the intensity of associated movement. Mild alerting stimuli produced stereotyped tachypnoeic responses, without affecting heart rate: tapping the chamber raised respiratory rate from 117+/-7 to 430+/-15 cpm; sudden side move--from 134+/-13 to 487+/-16 cpm, and turning on lights--from 136+/-12 to 507+/-14 cpm (n=10; p<0.01 for all; no inter-strain differences). We conclude that: i) sniffing is an integral part of the generalized arousal response and does not depend on the modality of sensory stimuli; ii) tachypnoea is a sensitive index of arousal; and iii) respiratory rate is tightly correlated with motor activity.
Anguera, Joaquin A.; Lyman, Kyle; Zanto, Theodore P.; Bollinger, Jacob; Gazzaley, Adam
Executive response functions can be affected by preceding events, even if they are no longer associated with the current task at hand. For example, studies utilizing the stop signal task have reported slower response times to “GO” stimuli when the preceding trial involved the presentation of a “STOP” signal. However, the neural mechanisms that underlie this behavioral after-effect are unclear. To address this, behavioral and electroencephalography (EEG) measures were examined in 18 young adults (18–30 years) on “GO” trials following a previously “Successful Inhibition” trial (pSI), a previously “Failed Inhibition” trial (pFI), and a previous “GO” trial (pGO). Like previous research, slower response times were observed during both pSI and pFI trials (i.e., “GO” trials that were preceded by a successful and unsuccessful inhibition trial, respectively) compared to pGO trials (i.e., “GO” trials that were preceded by another “GO” trial). Interestingly, response time slowing was greater during pSI trials compared to pFI trials, suggesting executive control is influenced by both task set switching and persisting motor inhibition processes. Follow-up behavioral analyses indicated that these effects resulted from between-trial control adjustments rather than repetition priming effects. Analyses of inter-electrode coherence (IEC) and inter-trial coherence (ITC) indicated that both pSI and pFI trials showed greater phase synchrony during the inter-trial interval compared to pGO trials. Unlike the IEC findings, differential ITC was present within the beta and alpha frequency bands in line with the observed behavior (pSI > pFI > pGO), suggestive of more consistent phase synchrony involving motor inhibition processes during the ITI at a regional level. These findings suggest that between-trial control adjustments involved with task-set switching and motor inhibition processes influence subsequent performance, providing new insights into the
Casini, Laurence; Roll, Jean-Pierre; Romaiguère, Patricia
We studied the relationship between the velocity of movement illusion and the activity level of primary motor area (M1) and of the left angular gyrus (AG) in humans. To induce illusory movement perception, we applied co-vibration at different frequencies on tendons of antagonistic muscle groups. Since it is well established that the velocity of illusory movement is related to the difference in vibration frequency applied to two antagonistic muscles, we compared magnetoencephalography (MEG) signals recorded in two conditions of co-vibration: in the "fast illusion" condition a frequency difference of 80 Hz was applied on the tendons of the right wrist extensor and flexor muscle groups, whereas in the "slow illusion" condition a frequency difference of 40 Hz was applied on the same muscle groups. The dipole strength, reflecting the activity level of structures, was measured over M1 and the left AG in two different time-periods: 0-400 and 400-800 ms in each condition. Our results showed that the activity level of the AG was similar in both conditions whatever the time-period, whereas the activity level of M1 was higher in the "fast illusion" condition compared to the "slow illusion" condition from 400 ms after the vibration onset only. The data suggest that the two structures differently contributed to the perception of illusory movements. Our hypothesis is that M1 would be involved in the coding of cinematic parameters of the illusory movement but not the AG.
Speer, Nicole K; Reynolds, Jeremy R; Swallow, Khena M; Zacks, Jeffrey M
To understand and remember stories, readers integrate their knowledge of the world with information in the text. Here we present functional neuroimaging evidence that neural systems track changes in the situation described by a story. Different brain regions track different aspects of a story, such as a character's physical location or current goals. Some of these regions mirror those involved when people perform, imagine, or observe similar real-world activities. These results support the view that readers understand a story by simulating the events in the story world and updating their simulation when features of that world change.
Speer, Nicole K.; Reynolds, Jeremy R.; Swallow, Khena M.; Zacks, Jeffrey M.
To understand and remember stories, readers integrate their knowledge of the world with information in the text. Here we present functional neuroimaging evidence that neural systems track changes in the situation described by a story. Different brain regions track different aspects of a story, such as a character’s physical location or current goals. Some of these regions mirror those involved when people perform, imagine, or observe similar real-world activities. These results support the view that readers understand a story by simulating the events in the story world and updating their simulation when features of that world change. PMID:19572969
Deglincerti, Alessia; Haremaki, Tomomi; Warmflash, Aryeh; Sorre, Benoit; Brivanlou, Ali H.
The TGFβ signaling pathway is a crucial regulator of developmental processes and disease. The activity of TGFβ ligands is modulated by various families of soluble inhibitors that interfere with the interactions between ligands and receptors. In an unbiased, genome-wide RNAi screen to identify genes involved in ligand-dependent signaling, we unexpectedly identified the BMP/Activin/Nodal inhibitor Coco as an enhancer of TGFβ1 signaling. Coco synergizes with TGFβ1 in both cell culture and Xenopus explants. Molecularly, Coco binds to TGFβ1 and enhances TGFβ1 binding to its receptor Alk5. Thus, Coco acts as both an inhibitor and an enhancer of signaling depending on the ligand it binds. This finding raises the need for a global reconsideration of the molecular mechanisms regulating TGFβ signaling. PMID:26116664
Deglincerti, Alessia; Haremaki, Tomomi; Warmflash, Aryeh; Sorre, Benoit; Brivanlou, Ali H
The TGFβ signaling pathway is a crucial regulator of developmental processes and disease. The activity of TGFβ ligands is modulated by various families of soluble inhibitors that interfere with the interactions between ligands and receptors. In an unbiased, genome-wide RNAi screen to identify genes involved in ligand-dependent signaling, we unexpectedly identified the BMP/Activin/Nodal inhibitor Coco as an enhancer of TGFβ1 signaling. Coco synergizes with TGFβ1 in both cell culture and Xenopus explants. Molecularly, Coco binds to TGFβ1 and enhances TGFβ1 binding to its receptor Alk5. Thus, Coco acts as both an inhibitor and an enhancer of signaling depending on the ligand it binds. This finding raises the need for a global reconsideration of the molecular mechanisms regulating TGFβ signaling.
During the six months of funding we have focused first on the completion of the research begun at the University of Washington in the previous funding cycle. Specifically, we developed a method to polymerize oriented networks of microtubules on lithographically patterned surfaces (M.S. thesis Robert Doot). The properties of active transport have been studied detail, yielding insights into the dispersion mechanisms (Nitta et al.). The assembly of multifunctional structures with a microtubule core has been investigated (Ramachandran et al.). Isaac Luria (B.S. in physics, U. of Florida 2005) worked on the directed assembly of nanoscale, non-equilibrium structures as a summer intern. He is now a graduate student in my group at the University of Florida. T. Nitta and H. Hess: Dispersion in Active Transport by Kinesin-Powered Molecular Shuttles, Nano Letters, 5, 1337-1342 (2005) S. Ramachandran, K.-H. Ernst, G. D. Bachand, V. Vogel, H. Hess*: Selective Loading of Kinesin-Powered Molecular Shuttles with Protein Cargo and its Application to Biosensing, submitted to Small (2005)
Zheng, Maohua; Gorelenkova, Olga; Yang, Jiong; Feng, Zhaoyang
Motor activity of Caenorhabditis elegans is widely used to study the mechanisms ranging from basic neuronal functions to human neurodegenerative diseases. It may also serve as a paradigm to screen for potential therapeutic reagents treating these diseases. Here, we developed an automated, 96-well plate and liquid phase based system that quantifies nematode motor activity in real time. Using this system, we identified an adult-onset, ageing-associated motor activity loss in a transgenic nematode line expressing human pathogenic G2019S mutant LRRK2 (leucine-rich repeat kinase 2), the leading genetic cause of Parkinson's disease characterized by dopaminergic neurodegeneration associated motor deficient mainly in elder citizens. Thus, our system may be used as a platform to screen for potential therapeutic drugs treating Parkinson's disease. It can also be used to monitor motor activity of nematodes in liquid phase at similar scenario.
Zhou, Hui-Hui; Wei, Min; Angelaki, Dora E.
The geometry of gaze stabilization during head translation requires eye movements to scale proportionally to the inverse of target distance. Such a scaling has indeed been demonstrated to exist for the translational vestibuloocular reflex (TVOR), as well as optic flow-selective translational visuomotor reflexes (e.g., ocular following, OFR). The similarities in this scaling by a neural estimate of target distance for both the TVOR and the OFR have been interpreted to suggest that the two reflexes share common premotor processing. Because the neural substrates of OFR are partly shared by those for the generation of pursuit eye movements, we wanted to know if the site of gain modulation for TVOR and OFR is also part of a major pathway for pursuit. Thus, in the present studies, we investigated in rhesus monkeys whether initial eye velocity and acceleration during the open-loop portion of step ramp pursuit scales with target distance. Specifically, with visual motion identical on the retina during tracking at different distances (12, 24, and 60 cm), we compared the first 80 ms of horizontal pursuit. We report that initial eye velocity and acceleration exhibits either no or a very small dependence on vergence angle that is at least an order of magnitude less than the corresponding dependence of the TVOR and OFR. The results suggest that the neural substrates for motor scaling by target distance remain largely distinct from the main pathway for pursuit.
Ketcheson, Leah; Hauck, Janet; Ulrich, Dale
Despite evidence suggesting one of the earliest indicators of an eventual autism spectrum disorder diagnoses is an early motor delay, there remain very few interventions targeting motor behavior as the primary outcome for young children with autism spectrum disorder. The aim of this pilot study was to measure the efficacy of an intensive motor skill intervention on motor skills (Test of Gross Motor Development-2), physical activity (accelerometers), and socialization (Playground Observation of Peer Engagement) in young children with autism spectrum disorder. A total of 20 children with autism spectrum disorder aged 4-6 years participated. The experimental group ( n = 11) participated in an 8-week intervention consisting of motor skill instruction for 4 h/day, 5 days/week. The control group ( n = 9) did not receive the intervention. A repeated-measures analysis of covariance revealed statistically significant differences between groups in all three motor outcomes, locomotor ( F(1, 14) = 10.07, p < 0.001, partial η(2) = 0.42), object control ( F(1, 14) = 12.90, p < 0.001, partial η(2) = 0.48), and gross quotient ( F(1, 14) = 15.61, p < 0.01, partial η(2) = 0.53). Findings shed light on the importance of including motor programming as part of the early intervention services delivered to young children with autism spectrum disorder.
Cochran, Jared C; Zhao, Yu Cheng; Wilcox, Dean E; Kull, F Jon
Kinesins are molecular motors that require a divalent metal ion (for example, Mg(2+)) to convert the energy of ATP hydrolysis into directed force production along microtubules. Here we present the crystal structure of a recombinant kinesin motor domain bound to Mn(2+) and ADP and report on a serine-to-cysteine substitution in the switch 1 motif of kinesin that allows its ATP hydrolysis activity to be controlled by adjusting the ratio of Mn(2+) to Mg(2+). This mutant kinesin binds ATP similarly in the presence of either metal ion, but its ATP hydrolysis activity is greatly diminished in the presence of Mg(2+). In human kinesin-1 and kinesin-5 as well as Drosophila melanogaster kinesin-10 and kinesin-14, this defect is rescued by Mn(2+), providing a way to control both the enzymatic activity and force-generating ability of these nanomachines.
Conti, Melissa M.; Ostock, Corinne Y.; George, Jessica A.; Goldenberg, Adam A.; Melikhov-Sosin, Mitchell; Nuss, Emily E.
Long-term treatment of Parkinson's disease with l-DOPA almost always leads to the development of involuntary movements termed l-DOPA-induced dyskinesia. Whereas hyperdopaminergic signaling in the basal ganglia is thought to cause dyskinesia, alterations in primary motor cortex (M1) activity are also prominent during dyskinesia, suggesting that the cortex may represent a therapeutic target. The present study used the rat unilateral 6-hydroxydopamine lesion model of Parkinson's disease to characterize in vivo changes in GABA and glutamate neurotransmission within M1 and determine their contribution to behavioral output. 6-Hydroxydopamine lesion led to parkinsonian motor impairment that was partially reversed by l-DOPA. Among sham-lesioned rats, l-DOPA did not change glutamate or GABA efflux. Likewise, 6-hydroxydopamine lesion did not impact GABA or glutamate among rats chronically treated with saline. However, we observed an interaction of lesion and treatment whereby, among lesioned rats, l-DOPA given acutely (1 d) or chronically (14–16 d) reduced glutamate efflux and enhanced GABA efflux. Site-specific microinjections into M1 demonstrated that l-DOPA-induced dyskinesia was reduced by M1 infusion of a D1 antagonist, an AMPA antagonist, or a GABAA agonist. Overall, the present study demonstrates that l-DOPA-induced dyskinesia is associated with increased M1 inhibition and that exogenously enhancing M1 inhibition may attenuate dyskinesia, findings that are in agreement with functional imaging and transcranial magnetic stimulation studies in human Parkinson's disease patients. Together, our study suggests that increasing M1 inhibitory tone is an endogenous compensatory response designed to limit dyskinesia severity and that potentiating this response is a viable therapeutic strategy. SIGNIFICANCE STATEMENT Most Parkinson's disease patients will receive l-DOPA and eventually develop hyperkinetic involuntary movements termed dyskinesia. Such symptoms can be as
Berrier, Allison L; Jones, Christopher W; LaFlamme, Susan E
The binding of integrins to extracellular matrix triggers signals that promote cell spreading. We previously demonstrated that expression of the integrin beta1 cytoplasmic domain in the context of a chimeric transmembrane receptor with the Tac subunit of the interleukin-2 receptor (Tac-beta1) inhibits cell spreading. To study the mechanism whereby Tac-beta1 inhibits cell spreading, we examined the effect of Tac-beta1 on early signaling events following integrin engagement namely FAK and Src signaling. We infected primary fibroblasts with adenoviruses expressing Tac or Tac-beta1 and found that Tac-beta1 prevented FAK activation by inhibiting the phosphorylation of FAK at Tyr-397. In contrast, Src activation was maintained, as phosphorylation of Src at Tyr-419 and Tyr-530 were not responsive to expression of Tac-beta1. Importantly, adhesion-induced tyrosine phosphorylation of the Src substrates p130Cas and paxillin was inhibited, indicating that Src signaling was blocked by Tac-beta1. These Src-dependent signaling events were found to require FAK signaling. Our results suggest that Tac-beta1 inhibits cell spreading, at least in part, by preventing the phosphorylation of FAK at Tyr-397 and the assembly of signaling complexes necessary for phosphorylation of p130Cas and other downstream effectors.
Koenderink, Gijsje H.; Dogic, Zvonimir; Nakamura, Fumihiko; Bendix, Poul M.; MacKintosh, Frederick C.; Hartwig, John H.; Stossel, Thomas P.; Weitz, David A.
We describe an active polymer network in which processive molecular motors control network elasticity. This system consists of actin filaments cross-linked by filamin A (FLNa) and contracted by bipolar filaments of muscle myosin II. The myosin motors stiffen the network by more than two orders of magnitude by pulling on actin filaments anchored in the network by FLNa cross-links, thereby generating internal stress. The stiffening response closely mimics the effects of external stress applied by mechanical shear. Both internal and external stresses can drive the network into a highly nonlinear, stiffened regime. The active stress reaches values that are equivalent to an external stress of 14 Pa, consistent with a 1-pN force per myosin head. This active network mimics many mechanical properties of cells and suggests that adherent cells exert mechanical control by operating in a nonlinear regime where cell stiffness is sensitive to changes in motor activity. This design principle may be applicable to engineering novel biologically inspired, active materials that adjust their own stiffness by internal catalytic control.
Doulah, Abul Barkat Mollah Sayeed Ud; Fattah, Shaikh Anowarul; Zhu, Wei-Ping; Ahmad, M Omair
A feature extraction scheme based on discrete cosine transform (DCT) of electromyography (EMG) signals is proposed for the classification of normal event and a neuromuscular disease, namely the amyotrophic lateral sclerosis. Instead of employing DCT directly on EMG data, it is employed on the motor unit action potentials (MUAPs) extracted from the EMG signal via a template matching-based decomposition technique. Unlike conventional MUAP-based methods, only one MUAP with maximum dynamic range is selected for DCT-based feature extraction. Magnitude and frequency values of a few high-energy DCT coefficients corresponding to the selected MUAP are used as the desired feature which not only reduces computational burden, but also offers better feature quality with high within-class compactness and between-class separation. For the purpose of classification, the K-nearest neighbourhood classifier is employed. Extensive analysis is performed on clinical EMG database and it is found that the proposed method provides a very satisfactory performance in terms of specificity, sensitivity and overall classification accuracy.
Faraji, Jamshid; Soltanpour, Nabiollah; Moeeini, Reza; Hosseini, Seyed Abedin; Pakdel, Shiva; Moharrerie, Alireza; Arjang, Kaveh; Soltanpour, Nasrin; Metz, Gerlinde A S
Spontaneous vertical and horizontal exploratory movements are integral components of rodent behavior. Little is known, however, about the structural and functional consequences of restricted spontaneous exploration. Here, we report two experiments to probe whether restriction in vertical activity (rearing) in rats could induce neuro-hormonal and behavioral disturbances. Rearing movements in rats were deprived for 3h/day for 30 consecutive days by placing the animal into a circular tunnel task. Rats temporarily deprived of rearing behavior showed elevated plasma corticosterone levels but no detectable psychological distress and/or anxiety-related behavior within an elevated plus maze. However, rats emitted a greater number of 22-kHz ultrasonic vocalizations and spent significantly more time vocalizing than controls when deprived of their rearing behavior. Despite intact spatial performance within wet- and dry-land spatial tasks, rearing-deprived rats also exhibited a significant alteration in search strategies within both spatial tasks along with reduced volume and neuron number in the hippocampal subregion CA2. These data suggest a new approach to test the importance of free exploratory behavior in endocrine and structural manifestations. The results support a central role of the CA2 in spontaneous exploratory behavior and vulnerability to psychological stress.
Al-Fandi, M; Jaradat, M A K; Fandi, K; Beech, J P; Tegenfeldt, J O; Yih, T C
Active micromixers with rotating elements are attractive microfluidic actuators in many applications because of their mixing ability at a short distance. However, miniaturising the impeller design poses technical challenges including the fabrication and driving means. As a possible solution inspired by macro magnetic bar-stirrers, this study proposes the use of tethered, rotating bacteria as mixing elements. A tethered cell is a genetically engineered, harmless Escherichia coli (E. coli) attached to a surface by a single, shortened flagellum. The tethered flagellum acts as a pivot around which the entire cell body smoothly rotates. Videomicroscopy, image analysis and computational fluid dynamics (CFD) are utilised to demonstrate a proof-of-concept for the micro mixing process. Flow visualisation experiments show that a approximately 3 microm long tethered E. coli rotating at approximately 240 rpm can circulate a 1 microm polystyrene bead in the adjacent area at an average speed of nearly 4 microm/s. The Peclet (Peb) number for the stirred bead is evaluated to approximately 4. CFD simulations show that the rotary motion of a tethered E. coli rotating at 240 rpm can generate fluid velocities, up to 37 microm/s bordering the cell envelop. Based on these simulations, the Strouhal number (St) is calculated to about 2. This hybrid bio-inorganic micromxer could be used as a local, disposable mixer.
Grove, CA, November, 2014. [in press, refereed]. C . Gianelli, L. Xu, and J. Li, " Active Sonar Systems in the Presence of Strong Direct Blast", Oceans...3. DATES COVERED (From - To) Oct. 01, 2014-Sept. 30, 2015 4. TITLE AND SUBTITLE Enhanced Multistatic Active Sonar via Innovative Signal... active sonar (CAS) in the presence of strong direct blast is studied for the Doppler-tolerant linear frequency modulation waveform. A receiver design
DATES COVERED (From - To) Oct. 01. 2013-Sept. 30, 2014 4. TITLE AND SUBTITLE Enhanced Multistatic Active Sonar via Innovative Signal Processing 5a...DISTRIBUTION AVAILABILITY STATEMENT Approved for Public Release; Distribution is Unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT Pulsed active sonar ...PAS) and continuous active sonar (CAS) in the presence of strong direct blast are studied for the Doppler-tolerant linear frequency modulation
Lo, Men-Tzung; Chiang, Wei-Yin; Hsieh, Wan-Hsin; Escobar, Carolina; Buijs, Ruud M; Hu, Kun
One evolutionary adaptation in motor activity control of animals is the anticipation of food that drives foraging under natural conditions and is mimicked in laboratory with daily scheduled food availability. Food anticipation is characterized by increased activity a few hours before the feeding period. Here we report that 2-h food availability during the normal inactive phase of rats not only increases activity levels before the feeding period but also alters the temporal organization of motor activity fluctuations over a wide range of time scales from minutes up to 24 h. We demonstrate this multiscale alteration by assessing fractal patterns in motor activity fluctuations-similar fluctuation structure at different time scales-that are robust in intact animals with ad libitum food access but are disrupted under food restriction. In addition, we show that fractal activity patterns in rats with ad libitum food access are also perturbed by lesion of the dorsomedial hypothalamic (DMH)-a neural node that is involved in food anticipatory behavior. Instead of further disrupting fractal regulation, food restriction restores the disrupted fractal patterns in these animals after the DMH lesion despite the persistence of the 24-h rhythms. This compensatory effect of food restriction is more clearly pronounced in the same animals after the additional lesion of the suprachiasmatic nucleus (SCN)-the central master clock in the circadian system that generates and orchestrates circadian rhythms in behavior and physiological functions in synchrony with day-night cycles. Moreover, all observed influences of food restriction persist even when data during the food anticipatory and feeding period are excluded. These results indicate that food restriction impacts dynamics of motor activity at different time scales across the entire circadian/daily cycle, which is likely caused by the competition between the food-induced time cue and the light-entrained circadian rhythm of the SCN. The
Lo, Men-Tzung; Chiang, Wei-Yin; Hsieh, Wan-Hsin; Escobar, Carolina; Buijs, Ruud M.; Hu, Kun
One evolutionary adaptation in motor activity control of animals is the anticipation of food that drives foraging under natural conditions and is mimicked in laboratory with daily scheduled food availability. Food anticipation is characterized by increased activity a few hours before the feeding period. Here we report that 2-h food availability during the normal inactive phase of rats not only increases activity levels before the feeding period but also alters the temporal organization of motor activity fluctuations over a wide range of time scales from minutes up to 24 h. We demonstrate this multiscale alteration by assessing fractal patterns in motor activity fluctuations—similar fluctuation structure at different time scales—that are robust in intact animals with ad libitum food access but are disrupted under food restriction. In addition, we show that fractal activity patterns in rats with ad libitum food access are also perturbed by lesion of the dorsomedial hypothalamic (DMH)—a neural node that is involved in food anticipatory behavior. Instead of further disrupting fractal regulation, food restriction restores the disrupted fractal patterns in these animals after the DMH lesion despite the persistence of the 24-h rhythms. This compensatory effect of food restriction is more clearly pronounced in the same animals after the additional lesion of the suprachiasmatic nucleus (SCN)—the central master clock in the circadian system that generates and orchestrates circadian rhythms in behavior and physiological functions in synchrony with day-night cycles. Moreover, all observed influences of food restriction persist even when data during the food anticipatory and feeding period are excluded. These results indicate that food restriction impacts dynamics of motor activity at different time scales across the entire circadian/daily cycle, which is likely caused by the competition between the food-induced time cue and the light-entrained circadian rhythm of the
Sun, Hong; Li, Li; Vercherat, Cécile; Gulbagci, Neriman Tuba; Acharjee, Sujata; Li, Jiali; Chung, Teng-Kai; Thin, Tin Htwe; Taneja, Reshma
Satellite cells play a critical role in skeletal muscle regeneration in response to injury. Notch signaling is vital for satellite cell activation and myogenic precursor cell expansion but inhibits myogenic differentiation. Thus, precise spatial and temporal regulation of Notch activity is necessary for efficient muscle regeneration. We report that the basic helix-loop-helix transcription factor Stra13 modulates Notch signaling in regenerating muscle. Upon injury, Stra13−/− mice exhibit increased cellular proliferation, elevated Notch signaling, a striking regeneration defect characterized by degenerated myotubes, increased mononuclear cells, and fibrosis. Stra13−/− primary myoblasts also exhibit enhanced Notch activity, increased proliferation, and defective differentiation. Inhibition of Notch signaling ex vivo and in vivo ameliorates the phenotype of Stra13−/− mutants. We demonstrate in vitro that Stra13 antagonizes Notch activity and reverses the Notch-imposed inhibition of myogenesis. Thus, Stra13 plays an important role in postnatal myogenesis by attenuating Notch signaling to reduce myoblast proliferation and promote myogenic differentiation. PMID:17502421
Chao, W; Olson, M S
During the past two decades, studies describing the chemistry and biology of PAF have been extensive. This potent phosphoacylglycerol exhibits a wide variety of physiological and pathophysiological effects in various cells and tissues. PAF acts, through specific receptors and a variety of signal transduction systems, to elicit diverse biochemical responses. Several important future directions can be enumerated for the characterization of PAF receptors and their attendant signalling mechanisms. The recent cloning and sequence analysis of the gene for the PAF receptor will allow a number of important experimental approaches for characterizing the structure and analysing the function of the various domains of the receptor. Using molecular genetic and immunological technologies, questions relating to whether there is receptor heterogeneity, the precise mechanism(s) for the regulation of the PAF receptor, and the molecular details of the signalling mechanisms in which the PAF receptor is involved can be explored. Another area of major significance is the examination of the relationship between the signalling response(s) evoked by PAF binding to its receptor and signalling mechanisms activated by a myriad of other mediators, cytokines and growth factors. A very exciting recent development in which PAF receptors undoubtedly play a role is in the regulation of the function of various cellular adhesion molecules. Finally, there remain many incompletely characterized physiological and pathophysiological situations in which PAF and its receptor play a crucial signalling role. Our laboratory has been active in the elucidation of several tissue responses in which PAF exhibits major autocoid signalling responses, e.g. hepatic injury and inflammation, acute and chronic pancreatitis, and cerebral stimulation and/or trauma. As new experimental strategies are developed for characterizing the fine structure of the molecular mechanisms involved in tissue injury and inflammation, the
Kengyel, András; Bécsi, Bálint; Kónya, Zoltán; Sellers, James R; Erdődi, Ferenc; Nyitrai, Miklós
The unconventional myosin 16 (Myo16), which may have a role in regulation of cell cycle and cell proliferation, can be found in both the nucleus and the cytoplasm. It has a unique, eight ankyrin repeat containing pre-motor domain, the so-called ankyrin domain (My16Ank). Ankyrin repeats are present in several other proteins, e.g., in the regulatory subunit (MYPT1) of the myosin phosphatase holoenzyme, which binds to the protein phosphatase-1 catalytic subunit (PP1c). My16Ank shows sequence similarity to MYPT1. In this work, the interactions of recombinant and isolated My16Ank were examined in vitro. To test the effects of My16Ank on myosin motor function, we used skeletal muscle myosin or nonmuscle myosin 2B. The results showed that My16Ank bound to skeletal muscle myosin (K D ≈ 2.4 µM) and the actin-activated ATPase activity of heavy meromyosin (HMM) was increased in the presence of My16Ank, suggesting that the ankyrin domain can modulate myosin motor activity. My16Ank showed no direct interaction with either globular or filamentous actin. We found, using a surface plasmon resonance-based binding technique, that My16Ank bound to PP1cα (K D ≈ 540 nM) and also to PP1cδ (K D ≈ 600 nM) and decreased its phosphatase activity towards the phosphorylated myosin regulatory light chain. Our results suggest that one function of the ankyrin domain is probably to regulate the function of Myo16. It may influence the motor activity, and in complex with the PP1c isoforms, it can play an important role in the targeted dephosphorylation of certain, as yet unidentified, intracellular proteins.
Festoff, B. W.; D'Andrea, M. R.; Citron, B. A.; Salcedo, R. M.; Smirnova, I. V.; Andrade-Gordon, P.
BACKGROUND: Mechanisms underlying neurodegeneration are actively sought for new therapeutic strategies. Transgenic, knockout and genetic mouse models greatly aid our understanding of the mechanisms for neuronal cell death. A naturally occurring, autosomal recessive mutant, known as wobbler, and mice transgenic for familial amyotrophic lateral sclerosis (FALS) superoxide dismutase (SOD)1 mutations are available, but the molecular mechanisms remain equally unknown. Both phenotypes are detectable after birth. Wobbler is detectable in the third week of life, when homozygotes (wr/wr) exhibit prominent gliosis and significant motor neuron loss in the cervical, but not in lumbar, spinal cord segments. To address molecular mechanisms, we evaluated "death signals" associated with the multifunctional serine protease, thrombin, which leads to apoptotic motor neuronal cell death in culture by cleavage of a G-protein coupled, protease-activated receptor 1 (PAR-1). MATERIALS AND METHODS: Thrombin activities were determined with chromogenic substrate assays, Western immunoblots and immunohistochemistry were performed with anti-PAR-1 to observe localizations of the receptor and anti-GFAP staining was used to monitor astrocytosis. PAR-1 mRNA levels and locations were determined by reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridizations. Cell death was monitored with in situ DNA fragmentation assays. RESULTS: In preliminary studies we found a 5-fold increase in PAR-1 mRNA in cervical spinal cords from wr/wr, compared with wild-type (wt) littermates. Our current studies suggested that reactive astrocytosis and motor neuron cell death were causally linked with alterations in thrombin signaling. PAR-1 protein expression was increased, as demonstrated by immunocytochemistry and confirmed with in situ hybridization, in phenotypic wr/wr motor neurons, compared with wt, but not in astrocytes. This increase was much greater in cervical, compared with lumbar
Saletin, Jared M; Coon, William G; Carskadon, Mary A
Attention deficit hyperactivity disorder (ADHD) is associated with deficits in motor learning and sleep. In healthy adults, overnight improvements in motor skills are associated with sleep spindle activity in the sleep electroencephalogram (EEG). This association is poorly characterized in children, particularly in pediatric ADHD. Polysomnographic sleep was monitored in 7 children with ADHD and 14 typically developing controls. All children were trained on a validated motor sequence task (MST) in the evening with retesting the following morning. Analyses focused on MST precision (speed-accuracy trade-off). NREM Stage 2 sleep EEG power spectral analyses focused on spindle-frequency EEG activity in the sigma (12-15 Hz) band. The ADHD group demonstrated a selective decrease in power within the sigma band. Evening MST precision was lower in ADHD, yet no difference in performance was observed following sleep. Moreover, ADHD status moderated the association between slow sleep spindle activity (12-13.5 Hz) and overnight improvement; spindle-frequency EEG activity was positively associated with performance improvements in children with ADHD but not in controls. These data highlight the importance of sleep in supporting next-day behavior in ADHD while indicating that differences in sleep neurophysiology may contribute to deficits in this population.
Acevedo, María Belén; Pautassi, Ricardo Marcos; Spear, Norman E.; Spear, Linda P.
Rationale It is important to study age-related differences that may put adolescents at risk for alcohol-related problems. Adolescents seem less sensitive to the aversive effects of ethanol than adults. Less is known of appetitive effects of ethanol and stress-modulation of these effects. Objectives To describe effects of acute social or restraint stress on ethanol-precipitated locomotor activity (LMA), in adolescent and adult rats. Effects of activation of the kappa system on ethanol-induced LMA were also evaluated. Methods Adolescent or adult rats were restrained for 90 min, exposed to social deprivation stress for 90 or 180 min or administered the kappa agonist U62,066E before being given ethanol and assessed for LMA. Results Adolescents were significantly more sensitive to the stimulating, and less sensitive to the sedative, effects of ethanol than adults. Basal locomotion was significantly increased by social deprivation stress in adult, but not in adolescent, rats. U62,066E significantly reduced basal and ethanol-induced locomotion in the adolescents. Corticosterone and progesterone levels were significantly higher in adolescents than in adults. Conclusions Adolescents exhibit greater sensitivity to ethanol-induced LMA and reduced sensitivity to ethanol-induced motor sedation than adult rats. Ethanol’s effects on motor activity were not affected by acute stress. Unlike adults, adolescents were insensitive to acute restraint and social deprivation stress, but exhibited motor depression after activation of the endogenous kappa opioid receptor system. PMID:23775530
Liu, Jie; Zhang, Bi; Lei, Haoyun; Feng, Zhaoyang; Liu, Jianfeng; Hsu, Ao-Lin; Xu, X Z Shawn
Aging is characterized by a progressive decline in multiple physiological functions (i.e., functional aging). As animals age, they exhibit a gradual loss in motor activity, but the underlying mechanisms remain unclear. Here we approach this question in C. elegans by functionally characterizing its aging nervous system and muscles. We find that motor neurons exhibit a progressive functional decline, beginning in early life. Surprisingly, body-wall muscles, which were previously thought to undergo functional aging, do not manifest such a decline until mid-late life. Notably, motor neurons first develop a deficit in synaptic vesicle fusion followed by that in quantal size and vesicle docking/priming, revealing specific functional deteriorations in synaptic transmission. Pharmacological stimulation of synaptic transmission can improve motor activity in aged animals. These results uncover a critical role for the nervous system in age-dependent motor activity decline in C. elegans and provide insights into how functional aging occurs in this organism.
Zhao, Xiaojie; Zhang, Hang; Song, Sutao; Ye, Qing; Guo, Jia; Yao, Li
Motor imagery training is an effective approach for motor skill learning and motor function rehabilitation. As a novel method of motor imagery training, real-time fMRI (rtfMRI) enables individuals to acquire self-control of localized brain activation, achieving desired changes in behavior. The regulation of target region activation by rtfMRI often alters the activation of related brain regions. However, the interaction between the target region and these related regions is unclear. The Granger causality model (GCM) is a data-driven method that can explore the causal interaction between brain regions. In this study, we employed rtfMRI to train subjects to regulate the activation of the ipsilateral dorsal premotor area (dPMA) during motor imagery training, and we calculated the causal interaction of the dPMA with other motor-related regions based on the GCM. The results demonstrated that as the activity of the dPMA changed during rtfMRI training, the interaction of the target region with other related regions became significantly altered, and behavioral performance was improved after training. The altered interaction primarily exhibited as an increased unidirectional interaction from the dPMA to the other regions. These findings support the dominant role of the dPMA in motor skill learning via rtfMRI training and may indicate how activation of the target region interacts with the activation of other related regions. PMID:24379775
Cratty, Bryant J.
Intended for special education and physical education teachers, the handbook presents selected developmental sequences of activities based on the analysis of perceptual motor characteristics of groups of retarded and neurologically handicapped children. Four classifications of children and their perceptual motor characteristics are discussed: the…
Travers, Brittany G; Kana, Rajesh K; Klinger, Laura G; Klein, Christopher L; Klinger, Mark R
Motor-linked implicit learning is the learning of a sequence of movements without conscious awareness. Although motor symptoms are frequently reported in individuals with autism spectrum disorder (ASD), recent behavioral studies have suggested that motor-linked implicit learning may be intact in ASD. The serial reaction time (SRT) task is one of the most common measures of motor-linked implicit learning. The present study used a 3T functional magnetic resonance imaging scanner to examine the behavioral and neural correlates of real-time motor sequence learning in adolescents and adults with ASD (n = 15) compared with age- and intelligence quotient-matched individuals with typical development (n = 15) during an SRT task. Behavioral results suggested less robust motor sequence learning in individuals with ASD. Group differences in brain activation suggested that individuals with ASD, relative to individuals with typical development, showed decreased activation in the right superior parietal lobule (SPL) and right precuneus (Brodmann areas 5 and 7, and extending into the intraparietal sulcus) during learning. Activation in these areas (and in areas such as the right putamen and right supramarginal gyrus) was found to be significantly related to behavioral learning in this task. Additionally, individuals with ASD who had more severe repetitive behavior/restricted interest symptoms demonstrated greater decreased activation in these regions during motor learning. In conjunction, these results suggest that the SPL may play an important role in motor learning and repetitive behavior in individuals with ASD.
Melo, Paula R; Belísio, Aline S; Menezes, Alexandre A L; Azevedo, Carolina V M
The effect of puberty on circadian rhythmicity in nonhuman primates has been little studied, even though it has been demonstrated that puberty-related changes in circadian activity rhythm occur in a number of species, including humans. To characterize the motor activity rhythm during puberty in common marmosets (Callithrix jacchus), six animals was continuously monitored by actimeters between their 5th and 12th months of age. The animals were housed with their families in outdoor cages under seminatural conditions. Onset of puberty was determined from fecal estrogen and progesterone levels in females and androgen levels in males. The spectral power of the circadian component stabilized later in the last two animals to enter puberty. The bimodal characteristic of the active phase in this species became progressively more apparent over the course of the months in which the mean temperature was highest, irrespective of the animal's age. Although the onset of activity advanced after entry into puberty, this parameter showed a strong correlation with sunrise, indicating that seasonality influences this variable. Neither age nor climatic factors included in the regression model influenced the differences in phase angles between sunrise and onset of activity, and between sunset and offset of activity. Total activity was the only parameter influenced by age in the regression model, showing an increase after entry into puberty. Despite the evidence of pubertal influence on both the circadian component and total activity, under seminatural conditions seasonal factors may have a more important effect on motor activity rhythm in common marmosets.
Gruhn, Matthias; Rosenbaum, Philipp; Bockemühl, Till; Büschges, Ansgar
Animals and humans need to move deftly and flexibly to adapt to environmental demands. Despite a large body of work on the neural control of walking in invertebrates and vertebrates alike, the mechanisms underlying the motor flexibility that is needed to adjust the motor behavior remain largely unknown. Here, we investigated optomotor-induced turning and the neuronal mechanisms underlying the differences between the leg movements of the two body sides in the stick insect Carausius morosus. We present data to show that the generation of turning kinematics in an insect are the combined result of descending unilateral commands that change the leg motor output via task-specific modifications in the processing of local sensory feedback as well as modification of the activity of local central pattern generating networks in a body-side-specific way. To our knowledge, this is the first study to demonstrate the specificity of such modifications in a defined motor task. DOI: http://dx.doi.org/10.7554/eLife.13799.001 PMID:27130731
Meerarani, Purushothaman; Reiterer, Gudrun; Toborek, Michal; Hennig, Bernhard
Dietary zinc has potent antioxidant and anti-inflammatory properties and is a critical component of peroxisome proliferator-activated receptor (PPAR) gene expression and regulation. To assess the protective mechanisms of PPARgamma in endothelial cell dysfunction and the role of zinc in the modulation of PPARgamma signaling, cultured porcine pulmonary artery endothelial cells were exposed to the membrane-permeable zinc chelator N,N,N'N'-tetrakis (2-pyridylmethyl)-ethylene diamine (TPEN), thiazolidinedione (TZD; PPARgamma agonist) or bisphenol A diglycidyl ether (BADGE; PPARgamma antagonist). Subsequently, endothelial cells were activated by treatment with linoleic acid (90 micro mol/L) for 6 h. Zinc chelation by TPEN increased the DNA binding activity of nuclear factor (NF)-kappaB and activator protein (AP)-1, decreased PPARgamma expression and activation as well as up-regulated interleukin (IL)-6 expression and production. These effects were fully reversed by zinc supplementation. In addition, exposure to TZD down-regulated linoleic acid-induced DNA binding activity of NF-kappaB and AP-1, whereas BADGE further induced activation of these oxidative stress-sensitive transcription factors. Most importantly, the TZD-mediated down-regulation of NF-kappaB and AP-1 and reduced inflammatory response were impaired during zinc chelation. These data suggest that zinc plays a critical role in PPARgamma signaling in linoleic acid-induced endothelial cell activation and indicate that PPARgamma signaling is impaired during zinc deficiency.
Abril-Gil, Mar; Garcia-Just, Alba; Cambras, Trinitat; Pérez-Cano, Francisco J; Castellote, Cristina; Franch, Àngels; Castell, Margarida
The release of mediators by mast cells triggers allergic symptoms involving various physiological systems and, in the most severe cases, the development of anaphylactic shock compromising mainly the nervous and cardiovascular systems. We aimed to establish variables to objectively study the anaphylactic response (AR) after an oral challenge in an allergy model. Brown Norway rats were immunized by intraperitoneal injection of ovalbumin with alum and toxin from Bordetella pertussis. Specific immunoglobulin (Ig) E antibodies were developed in immunized animals. Forty days after immunization, the rats were orally challenged with the allergen, and motor activity, body temperature and serum mast cell protease concentration were determined. The anaphylaxis induced a reduction in body temperature and a decrease in the number of animal movements, which was inversely correlated with serum mast cell protease release. In summary, motor activity is a reliable tool for assessing AR and also an unbiased method for screening new anti-allergic drugs.
Buttarelli, Francesca R; Pontieri, Francesco E; Margotta, Vito; Palladini, Guido
Planaria, the most primitive example of centralization and cephalization of the nervous system along phylogeny, shows specific stereotyped behavioral patterns following exposure to drugs acting on neural transmission. In this study, the authors investigated the effects of exposure to the synthetic cannabinoid receptor agonist WTN55212.2 on motor activity in planaria. WTN55212.2 produced dose-dependent stimulation of motor behavior. High doses of the drug caused stereotyped activities identical to those seen previously with opioid agonists. These effects were antagonized by coexposure to cannabinoid or opioid receptor antagonists. The results indicate that functional interactions between cannabinoid and opioid systems are highly conserved along phylogeny, at least at the behavioral level.
Ashley, Jason W; Ahn, Jaimo; Hankenson, Kurt D
The role of Notch signaling in osteoclast differentiation is controversial with conflicting experimental evidence indicating both stimulatory and inhibitory roles. Differences in experimental protocols and in vivo versus in vitro models may explain the discrepancies between studies. In this study, we investigated cell autonomous roles of Notch signaling in osteoclast differentiation and function by altering Notch signaling during osteoclast differentiation using stimulation with immobilized ligands Jagged1 or Delta-like1 or by suppression with γ-secretase inhibitor DAPT or transcriptional inhibitor SAHM1. Stimulation of Notch signaling in committed osteoclast precursors resulted in larger osteoclasts with a greater number of nuclei and resorptive activity whereas suppression resulted in smaller osteoclasts with fewer nuclei and suppressed resorptive activity. Conversely, stimula