Aziz, Qasim; Fass, Ronnie; Gyawali, C Prakash; Miwa, Hiroto; Pandolfino, John E; Zerbib, Frank
Functional esophageal disorders consist of a disease category that present with esophageal symptoms (heartburn, chest pain, dysphagia, globus) not explained by mechanical obstruction (stricture, tumor, eosinophilic esophagitis), major motor disorders (achalasia, EGJ outflow obstruction, absent contractility, distal esophageal spasm, jackhammer esophagus), or gastroesophageal reflux disease (GERD). While mechanisms responsible are unclear, it is theorized that visceral hypersensitivity and hypervigilance play an important role in symptom generation, in the context of normal or borderline function. Treatments directed at improving borderline motor dysfunction or reducing reflux burden to sub-normal levels have limited success in symptom improvement. In contrast, strategies focused on modulating peripheral triggering and central perception are mechanistically viable and clinically meaningful. However, outcome data from these treatment options are limited. Future research needs to focus on understanding mechanisms underlying visceral hypersensitivity and hypervigilance so that appropriate targets and therapies can be developed.
Paine, Peter A; Hamdy, Shaheen; Chitnis, Xavier; Gregory, Lloyd J; Giampietro, Vincent; Brammer, Mick; Williams, Steve; Aziz, Qasim
Esophageal acid exposure induces sensory and motility changes in the upper gastrointestinal tract; however, the mechanisms involved and the effects on activity in the brain regions that control swallowing are unknown. The aim of this study was to examine functional changes in the cortical swallowing network as a result of esophageal acidification using functional magnetic resonance imaging (fMRI). Seven healthy volunteers (3 female, age range=20-30 years) were randomized to receive either a 0.1 M hydrochloric acid or (control) saline infusion for 30 min into the distal esophagus. Postinfusion, subjects underwent four 8 min blocks of fMRI over 1 h. These alternated between 1 min swallowing water boluses and 1 min rest. Three-dimensional cluster analysis for group brain activation during swallowing was performed together with repeated-measures ANOVA for differences between acid and saline. After acid infusion, swallowing-induced activation was seen predominantly in postcentral gyrus (p<0.004). ANOVA comparison of acid with saline showed a significant relative reduction in activation during swallowing of the precentral gyrus (M1) BA 4 (p<0.008) in response to acid infusion. No areas of increased cortical activation were identified with acid vs. saline during swallowing. Esophageal acidification inhibits motor and association cortical areas during a swallowing task, probably via changes in vagal afferent or nociceptive input from the esophagus. This mechanism may play a protective role, facilitating acid clearance by reduced descending central motor inhibition of enteric/spinal reflexes, or by preventing further ingestion of injurious agents.
Cadranel, S.; Di Lorenzo, C.; Rodesch, P.; Piepsz, A.; Ham, H.R. )
The aim of the present study was to investigate esophageal motor function by means of krypton-81m esophageal transit scintigraphy and to compare the results with the functional and morphological data obtained by means of triple lumen manometry and endoscopy. In acute and subacute stages of the disease, all clinical, anatomical, and functional parameters were in good agreement, revealing significant impairment. In chronic stages, the severity of the dysphagia was not correlated to the importance of the residual stenosis. Conversely, 81mKr esophageal transit and manometric's findings were in good agreement with the clinical symptoms, during the entire follow-up period ranging between 3 months to 7 years. The 81mKr test is undoubtedly the easiest and probably the most physiological technique currently available for long-term functional evaluation of caustic esophagitis.
Russell, C.O.; Pope, C.E.; Gannan, R.M.; Allen, F.D.; Velasco, N.; Hill, L.D.
The high incidence of dysphagia in patients with symptomatic gastroesophageal reflux (GER) but no evidence of peptic stricture suggests esophageal motor dysfunction. Conventional methods for detecting dysfunction (radiologic and manometric examinations) often fail to detect abnormality in these patients. Radionuclide transit (RT), a new method for detecting esophageal motor dysfunction, was used to prospectively assess function in 29 patients with symptomatic GER uncomplicated by stricture before and three months after antireflux surgery (HILL). The preoperative incidence of dysphagia and esophageal dysfunction was 73% and 52%, respectively. During operation (Hill repair), intraoperative measurement of the lower esophageal sphincter pressure was performed and the LESP raised to levels between 45 and 55 mmHg. The preoperative lower esophageal sphincter pressure was raised from a mean of 8.6 mmHg, to mean of 18.5 mmHg after operation. No patient has free reflux after operation. Postoperative studies on 20 patients demonstrated persistence of all preoperative esophageal dysfunction despite loss of dysphagia. RT has demonstrated a disorder of esophageal motor function in 52% of patients with symptomatic GER that may be responsible for impaired esophageal clearance. This abnormality is not contraindication to surgery. The results indicate that construction of an effective barrier to reflex corrects symptoms of reflux, even in the presence of impaired esophageal transit. Radionuclide transit is a safe noninvasive test for assessment of esophageal function.
Pandolfino, John E
Eosinophilic Esophagitis (EoE) is a chronic inflammatory disease of the esophagus triggered by an immune response that leads to symptoms of dysphagia, chest pain, and food impaction. EoE is a clinicopathologic syndrome that requires clinical symptoms and pathologic findings for a diagnosis. The inflammatory process and eosinophilic infiltration of the esophagus in EoE lead to fibrosis and structural changes within the esophagus that cause esophageal dysfunction. The biomechanics of the esophageal function in EoE have been explored using manometry, impedance planimetry, barium esophagograms, and endoscopic ultrasound. These studies have identified several biomechanical changes to the esophagus in EoE including pan-esophageal pressurization on manometry, changes in esophageal compliance with decreased distentisbility by impedance planimetry, decreased esophageal luminal diameter by esophagograms, and dysfunction in the esophageal longitudinal muscles by endoscopic ultrasound. Treatments for the disease involve dietary changes, immunosuppressive drugs, and dilation techniques. However, the data regarding the effect of these therapies on altering mechanical properties of the esophagus is limited. As the pathogenesis of esophageal dysfunction in EoE appears multifactorial, further study of the biomechanics of EoE is critical to better diagnose, monitor and treat the disease. PMID:23105995
Read, Andrew J; Pandolfino, John E
Eosinophilic Esophagitis (EoE) is a chronic inflammatory disease of the esophagus triggered by an immune response that leads to symptoms of dysphagia, chest pain, and food impaction. EoE is a clinicopathologic syndrome that requires clinical symptoms and pathologic findings for a diagnosis. The inflammatory process and eosinophilic infiltration of the esophagus in EoE lead to fibrosis and structural changes within the esophagus that cause esophageal dysfunction. The biomechanics of the esophageal function in EoE have been explored using manometry, impedance planimetry, barium esophagograms, and endoscopic ultrasound. These studies have identified several biomechanical changes to the esophagus in EoE including pan-esophageal pressurization on manometry, changes in esophageal compliance with decreased distentisbility by impedance planimetry, decreased esophageal luminal diameter by esophagograms, and dysfunction in the esophageal longitudinal muscles by endoscopic ultrasound. Treatments for the disease involve dietary changes, immunosuppressive drugs, and dilation techniques. However, the data regarding the effect of these therapies on altering mechanical properties of the esophagus is limited. As the pathogenesis of esophageal dysfunction in EoE appears multifactorial, further study of the biomechanics of EoE is critical to better diagnose, monitor and treat the disease.
Awad, R A
he occurrence of esophageal and gastric motor dysfunctions happens, when the software of the esophagus and the stomach is injured. This is really a program previously established in the enteric nervous system as a constituent of the newly called neurogastroenterology. The enteric nervous system is composed of small aggregations of nerve cells, enteric ganglia, the neural connections between these ganglia, and nerve fibers that supply effectors tissues, including the muscle of the gut wall. The wide range of enteric neuropathies that includes esophageal achalasia and gastroparesis highlights the importance of the enteric nervous system. A classification of functional gastrointestinal disorders based on symptoms has received attention. However, a classification based solely in symptoms and consensus may lack an integral approach of disease. As an alternative to the Rome classification, an international working team in Bangkok presented a classification of motility disorders as a physiology-based diagnosis. Besides, the Chicago Classification of esophageal motility was developed to facilitate the interpretation of clinical high-resolution esophageal pressure topography studies. This review covers exclusively the medical and surgical management of the esophageal and gastric motor dysfunction using evidence from well-designed studies. Motor control of the esophagus and the stomach, motor esophageal and gastric alterations, treatment failure, side effects of PPIs, overlap of gastrointestinal symptoms, predictors of treatment, burden of GERD medical management, data related to conservative treatment vs. antireflux surgery, and postsurgical esophagus and gastric motor dysfunction are also taken into account.
Valdovinos, Miguel A; Zavala-Solares, Monica R; Coss-Adame, Enrique
Esophageal hypomotility (EH) is characterized by abnormal esophageal peristalsis, either from a reduction or absence of contractions, whereas spastic motor disorders (SMD) are characterized by an increase in the vigor and/or propagation velocity of esophageal body contractions. Their pathophysiology is not clearly known. The reduced excitation of the smooth muscle contraction mediated by cholinergic neurons and the impairment of inhibitory ganglion neuronal function mediated by nitric oxide are likely mechanisms of the peristaltic abnormalities seen in EH and SMD, respectively. Dysphagia and chest pain are the most frequent clinical manifestations for both of these dysfunctions, and gastroesophageal reflux disease (GERD) is commonly associated with these motor disorders. The introduction of high-resolution manometry (HRM) and esophageal pressure topography (EPT) has significantly enhanced the ability to diagnose EH and SMD. Novel EPT metrics in particular the development of the Chicago Classification of esophageal motor disorders has enabled improved characterization of these abnormalities. The first step in the management of EH and SMD is to treat GERD, especially when esophageal testing shows pathologic reflux. Smooth muscle relaxants (nitrates, calcium channel blockers, 5-phosphodiesterase inhibitors) and pain modulators may be useful in the management of dysphagia or pain in SMD. Endoscopic Botox injection and pneumatic dilation are the second-line therapies. Extended myotomy of the esophageal body or peroral endoscopic myotomy (POEM) may be considered in highly selected cases but lack evidence.
Farmer, Adam D; Ruffle, James K; Aziz, Qasim
The Rome IV diagnostic criteria delineates 5 functional esophageal disorders which include functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia. These are a heterogenous group of disorders which, despite having characteristic symptom profiles attributable to esophageal pathology, fail to demonstrate any structural, motility or inflammatory abnormalities on standard clinical testing. These disorders are associated with a marked reduction in patient quality of life, not least considerable healthcare resources. Furthermore, the pathophysiology of these disorders is incompletely understood. In this narrative review we provide the reader with an introductory primer to the structure and function of esophageal perception, including nociception that forms the basis of the putative mechanisms that may give rise to symptoms in functional esophageal disorders. We also discuss the provocative techniques and outcome measures by which esophageal hypersensitivity can be established.
Yazaki, Etsuro; Woodland, Philip; Sifrim, Daniel
Esophageal function testing should be used for differential diagnosis of dysphagia. Dysphagia can be the consequence of hypermotility or hypomotility of the muscles of the esophagus. Decreased esophageal or esophagogastric junction distensibility can provoke dysphagia. The most well established esophageal dysmotility is achalasia. Other motility disorders can also cause dysphagia. High-resolution manometry (HRM) is the gold standard investigation for esophageal motility disorders. Simultaneous measurement of HRM and intraluminal impedance can be useful to assess motility and bolus transit. Impedance planimetry measures distensibility of the esophageal body and gastroesophageal junction in patients with achalasia and eosinophilic esophagitis.
Gravesen, Flemming H; Funch-Jensen, Peter; Gregersen, Hans; Drewes, Asbjørn Mohr
The esophagus serves to transport food and fluid from the pharynx to the stomach. Manometry has been the “golden standard” for the diagnosis of esophageal motility diseases for many decades. Hence, esophageal function is normally evaluated by means of manometry even though it reflects the squeeze force (force in radial direction) whereas the bolus moves along the length of esophagus in a distal direction. Force measurements in the longitudinal (axial) direction provide a more direct measure of esophageal transport function. The technique used to record axial force has developed from external force transducers over in-vivo strain gauges of various sizes to electrical impedance based measurements. The amplitude and duration of the axial force has been shown to be as reliable as manometry. Normal, as well as abnormal, manometric recordings occur with normal bolus transit, which have been documented using imaging modalities such as radiography and scintigraphy. This inconsistency using manometry has also been documented by axial force recordings. This underlines the lack of information when diagnostics are based on manometry alone. Increasing the volume of a bag mounted on a probe with combined axial force and manometry recordings showed that axial force amplitude increased by 130% in contrast to an increase of 30% using manometry. Using axial force in combination with manometry provides a more complete picture of esophageal motility, and the current paper outlines the advantages of using this method. PMID:19132762
Clarke, John O; Pandolfino, John E
High-resolution manometry has added significantly to our current understanding of esophageal motor function by providing improved detail and a data analysis paradigm that is more akin to an imaging format. Esophageal pressure topography provides a seamless dynamic representation of the pressure profile through the entire esophagus and thus, is able to eliminate movement artifact and also assess intrabolus pressure patterns as a surrogate for bolus transit mechanics. This has led to improved identification of anatomic landmarks and measurement of important physiological parameters (esophagogastric junction relaxation, distal latency, and contractile integrity). This research has bridged the gap into clinical practice by defining physiologically relevant phenotypes that may have prognostic significance and improve treatment decisions in achalasia, spasm, and hypercontractile disorders. However, more work is needed in determining the etiology of symptom generation in the context of normal or trivial motor dysfunction. This research will require new techniques to assess visceral hypersensitivity and alterations in central modulation of pain and discomfort.
Schneider, Jaycie; Ames, Marisa; DiCicco, Michael; Savage, Mason; Atkins, Clarke; Wood, Michael; Gookin, Jody L
An 8-week-old male domestic shorthair was presented to the Internal Medicine Service at North Carolina State University for regurgitation. Radiographic diagnosis of generalized esophageal dilation and failure of esophageal peristalsis were compatible with diagnosis of congenital megaesophagus. Endoscopic examination of the esophagus revealed a fibrous stricture just orad to the lower esophageal sphincter. Conservative management to increase the body condition and size of the kitten consisted of feeding through a gastrostomy tube, during which time the esophagus regained normal peristaltic function, the stricture orifice widened in size and successful balloon dilatation of the stricture was performed. Esophageal endoscopy should be considered to rule out a stricture near the lower esophageal sphincter in kittens with radiographic findings suggestive of congenital megaesophagus. Management of such kittens by means of gastrostomy tube feeding may be associated with a return of normal esophageal motility and widening of the esophageal stricture, and facilitate subsequent success of interventional dilation of the esophageal stricture.
Ratuapli, Shiva K; Hansel, Stephanie L; Umar, Sarah B; Burdick, George E; Ramirez, Francisco C; Fleischer, David E; Harris, Lucinda A; Lacy, Brian E; DiBaise, John K; Crowell, Michael D
Functional dysphagia (FD) is characterized by the presence of dysphagia without evidence of mechanical esophageal obstruction, GERD, and histopathology-based esophageal motor disorders. Dysphagia is common in older patients; however, there is a paucity of information regarding the type and frequency of peristaltic abnormalities compared to younger patients. Based on recently validated criteria for classification of weak peristalsis using high-resolution manometry (HRM), we hypothesized that older patients with FD would have more peristaltic defects detected by HRM compared to younger FD patients. A retrospective review of our motility database yielded 65 patients that met inclusion criteria. Patients were divided into two groups based on age (younger: <70 years; older: ≥70 years). Patients were interviewed, completed a quality-of-life questionnaire, and underwent solid-state HRM. The two groups differed in age but in no other demographic characteristics, severity of dysphagia, or quality of life. Dyspeptic symptoms, including nausea (p < 0.001), early satiety (p = 0.01), bloating (p = 0.02), and belching (p = 0.01), were also more prevalent in younger FD patients. Older age was associated with weak peristalsis involving frequent failed peristalsis, small proximal peristaltic defects (2-5 cm), and large proximal peristaltic defects (>5 cm) (p < 0.001). The mean contraction amplitude was also lower in the older group (p < 0.05). These data support the hypothesis that older patients with FD have a higher frequency of peristaltic abnormalities on HRM compared to younger patients. Older age was associated with increased frequency of weak peristalsis with small and large peristaltic defects.
... irritates the tissue. This problem is called gastroesophageal reflux (GERD). An autoimmune disorder called eosinophilic esophagitis also ... include: Cough Difficulty swallowing Painful swallowing Heartburn (acid reflux) Hoarseness Sore throat Exams and Tests The doctor ...
Neumann, Helmut; Neurath, Markus F; Vieth, Michael; Lever, Frederiek M; Meijer, Gert J; Lips, Irene M; McMahon, Barry P; Ruurda, J P; van Hillegersberg, R; Siersema, P; Levine, Marc S; Scharitzer, Martina; Pokieser, Peter; Zerbib, Frank; Savarino, Vincenzo; Zentilin, Patrizia; Savarino, Edoardo; Chan, Walter W
This paper reporting on techniques for esophageal evaluation and imaging and drugs for esophageal disease includes commentaries on endoscopy techniques including dye-based high-resolution and dye-less high-definition endoscopy; the shift from CT to MRI guidance in tumor delineation for radiation therapy; the role of functional lumen imaging in measuring esophageal distensibility; electrical stimulation of the lower esophageal sphincter (LES) as an alternative to fundoduplication for treatment of gastroesophageal reflux disease (GERD); the morphological findings of reflux esophagitis and esophageal dysmotility on double-contrast esophagography; the value of videofluoroscopy in assessing protecting mechanisms in patients with chronic reflux or swallowing disorders; targeting visceral hypersensitivity in the treatment of refractory GERD; and the symptoms and treatments of nighttime reflux and nocturnal acid breakthrough (NAB).
Zerbib, Frank; Roman, Sabine
With the development of high-resolution manometry and specific metrics to characterize esophageal motility, the Chicago Classification has become the gold standard for the diagnosis of esophageal motor disorders. Major and significant disorders, that is, never observed in healthy subjects, are achalasia, esophagogastric junction outflow obstruction, distal esophageal spasm, absent peristalsis, and hypercontractile (Jackhammer) esophagus. Achalasia subtyping is relevant to predict the response to endoscopic and surgical therapies as several studies suggest that, pneumatic dilation is less effective than Heller myotomy, in type III achalasia. Peroral endoscopic myotomy, initially developed in expert centers, is a promising technique for the treatment of achalasia. The medical therapeutic options for distal esophageal spasm and hypercontractile esophagus are smooth muscle relaxants and pain modulators. Intraesophageal injection of botulinum toxin might be an interesting option for treatment of these disorders but further studies are required to determine the optimal injection protocol and the best candidates based on manometric patterns. The treatment of hypotensive motility disorders is disappointing and relies mainly on dietary and lifestyle changes as no effective esophageal prokinetic is currently available.
LeSouëf, P N; Myers, N A; Landau, L I
Recurrent respiratory illnesses are frequent in infants following repair of esophageal atresia and functional abnormalities of respiratory and esophageal function are often seen in older children. Recurrent aspiration is a potential cause of these respiratory abnormalities, but a relationship between abnormalities of gastrointestinal and respiratory mechanics has not been adequately investigated. We sought an association between lower esophageal sphincter (LES) incompetence, gastroesophageal reflux (GER), and respiratory function abnormalities in 18 subjects (age 12 to 21 years) following repair of esophageal atresia (Vogt type 111B). In each subject, measurements were made of spirometry, lung volumes assessed by plethysmography, esophageal manometry recorded using a constantly infused fluid-filled trilumen catheter to assess LES pressure and esophageal motility, and esophageal pH monitoring to detect GER. Subjects were grouped according to the presence or absence of a radiologically supported diagnosis of pneumonia in the first 4 years of life. Lung volumes were mildly but significantly decreased in the "pneumonia" group compared with the "nonpneumonia" group. There was no association between abnormalities of respiratory function and abnormal LES pressure or the presence of GER. These data suggest that pneumonia in esophageal atresia infants is associated with mild long-term lung damage. LES dysfunction and GER do not appear to play a major role in this process.
Vicente-Vytopilova, Pavla; Tavernier, Béatrice; Sabia, Séverine; Dumurgier, Julien; Mazoyer, Bernard; Singh-Manoux, Archana; Tzourio, Christophe
Objective: The reserve hypothesis accounts for the lack of direct relationship between brain pathology and its clinical manifestations. Research has mostly focused on cognition; our objective is to examine whether the reserve hypothesis applies to motor function. We investigated whether education, a marker of reserve, modifies the association between white matter lesions (WMLs), a marker of vascular brain damage, and maximum walking speed (WS), an objective measure of motor function. We also examined the cross-sectional and longitudinal association between education and WS. Methods: Data are from 4,010 participants aged 65–85 years in the longitudinal Three-City–Dijon Study with up to 4 WS measures over 10 years. We examined the interaction between education and WMLs for baseline WS. We studied the association between education and repeated WS measures using linear mixed models, and the role of covariates in explaining the education-WS association. Results: Education was strongly associated with baseline WS; the difference in mean WS between the high and low education groups (0.145 m/s, 95% confidence interval = 0.125–0.165) was equivalent to 7.4 years of age. WMLs were associated with slow WS only in the low education group (p interaction = 0.026). WS declined significantly over time (−0.194 m/s/10 years, 95% confidence interval = −0.206, −0.182), but education did not influence rate of decline. Anthropometric characteristics, parental education, general health, and cognition had the strongest role in explaining the baseline education-WS association. Conclusions: Participants with more education were less susceptible to WMLs' effect on motor function. Higher education was associated with better motor performances but not with motor decline. These results are consistent with the passive reserve hypothesis. PMID:23803317
Miller, M; Chukoskie, L; Zinni, M; Townsend, J; Trauner, D
This project assessed dyspraxia in high-functioning school aged children with autism with a focus on Ideational Praxis. We examined the association of specific underlying motor function including eye movement with ideational dyspraxia (sequences of skilled movements) as well as the possible role of visual-motor integration in dyspraxia. We found that compared to IQ-, sex- and age-matched typically developing children, the children with autism performed significantly worse on: Ideational and Buccofacial praxis; a broad range of motor tests, including measures of simple motor skill, timing and accuracy of saccadic eye movements and motor coordination; and tests of visual-motor integration. Impairments in individual children with autism were heterogeneous in nature, although when we examined the praxis data as a function of a qualitative measure representing motor timing, we found that children with poor motor timing performed worse on all praxis categories and had slower and less accurate eye movements while those with regular timing performed as well as typical children on those same tasks. Our data provide evidence that both motor function and visual-motor integration contribute to dyspraxia. We suggest that dyspraxia in autism involves cerebellar mechanisms of movement control and the integration of these mechanisms with cortical networks implicated in praxis.
Heider, T Ryan; Behrns, Kevin E; Koruda, Mark J; Shaheen, Nicholas J; Lucktong, Tananchai A; Bradshaw, Barbara; Farrell, Timothy M
Patients with gastroesophageal reflux disease (GERD) and disordered esophageal motility are at risk for postoperative dysphagia, and are often treated with partial (270-degree) fundoplication as a strategy to minimize postoperative swallowing difficulties. Complete (360-degree) fundoplication, however, may provide more effective and durable reflux protection over time. Recently we reported that postfundoplication dysphagia is uncommon, regardless of preoperative manometric status and type of fundoplication. To determine whether esophageal function improves after fundoplication, we measured postoperative motility in patients in whom disordered esophageal motility had been documented before fundoplication. Forty-eight of 262 patients who underwent laparoscopic fundoplication between 1995 and 2000 satisfied preoperative manometric criteria for disordered esophageal motility (distal esophageal peristaltic amplitude < or =30 mm Hg and/or peristaltic frequency < or =80%). Of these, 19 had preoperative manometric assessment at our facility and consented to repeat study. Fifteen (79%) of these patients had a complete fundoplication and four (21%) had a partial fundoplication. Each patient underwent repeat four-channel esophageal manometry 29.5 +/- 18.4 months (mean +/- SD) after fundoplication. Distal esophageal peristaltic amplitude and peristaltic frequency were compared to preoperative data by paired t test. After fundoplication, mean peristaltic amplitude in the distal esophagus increased by 47% (56.8 +/- 30.9 mm Hg to 83.5 +/- 36.5 mm Hg; P < 0.001) and peristaltic frequency improved by 33% (66.4 +/- 28.7% to 87.6 +/- 16.3%; P < 0.01). Normal esophageal motor function was present in 14 patients (74%) after fundoplication, whereas in five patients the esophageal motor function remained abnormal (2 improved, 1 worsened, and 2 remained unchanged). Three patients with preoperative peristaltic frequencies of 0%, 10%, and 20% improved to 84%, 88%, and 50%, respectively
Mearin, Fermín; Rey, Enrique; Balboa, Agustín
This article discusses the most interesting studies on functional and motility gastrointestinal disorders presented in Digestive Diseases Week (DDW) in 2013. New data were reported on the clinical importance of functional gastrointestinal disorders (FGID) and on how they can produce numerous disturbances such as inflammatory bowel disease. These disturbances are associated with somatic functional disease and particularly with fatigue. In addition, new data have emerged on the physiopathology of these disorders, with some studies reporting that environmental factors and events in early infancy can favor their development. Data were also presented on how bile acids can increase susceptibility to diarrhea in patients with irritable bowel syndrome (IBS) and on how the type of food intake can favor the development of symptoms. More data are available on the presence of underlying celiac disease in patients with IBS, which should prompt us to investigate this disease in our patients. Likewise, indiscriminate application of a gluten-free diet in patients with IBS has been shown not to produce a clear improvement. Regarding the physiopathology of functional dyspepsia (FD), results have been presented on how psychological factors can modify gastric accommodation and how this is in turn related to visceral hypersensitivity and gastric emptying. Regarding therapy, mirtazapine can improve symptoms and lead to weight gain in patients with severe FD and substantial weight loss. Results were presented on new drugs for IBS such as ibodutant and on old drugs with new applications such as mesalazine and ebastine. The antinociceptive effect of linaclotide is now better understood and a meta-analysis has shown its effectiveness in IBS with constipation as the main symptom. In patients with constipation, pelvic floor dysynergy can be diagnosed by a simple clinical interview and rectal touch. More data are available on the efficacy of prucalopride (which has been shown to accelerate
Reddy, A. S.
Molecular motors that hydrolyze ATP and use the derived energy to generate force are involved in a variety of diverse cellular functions. Genetic, biochemical, and cellular localization data have implicated motors in a variety of functions such as vesicle and organelle transport, cytoskeleton dynamics, morphogenesis, polarized growth, cell movements, spindle formation, chromosome movement, nuclear fusion, and signal transduction. In non-plant systems three families of molecular motors (kinesins, dyneins, and myosins) have been well characterized. These motors use microtubules (in the case of kinesines and dyneins) or actin filaments (in the case of myosins) as tracks to transport cargo materials intracellularly. During the last decade tremendous progress has been made in understanding the structure and function of various motors in animals. These studies are yielding interesting insights into the functions of molecular motors and the origin of different families of motors. Furthermore, the paradigm that motors bind cargo and move along cytoskeletal tracks does not explain the functions of some of the motors. Relatively little is known about the molecular motors and their roles in plants. In recent years, by using biochemical, cell biological, molecular, and genetic approaches a few molecular motors have been isolated and characterized from plants. These studies indicate that some of the motors in plants have novel features and regulatory mechanisms. The role of molecular motors in plant cell division, cell expansion, cytoplasmic streaming, cell-to-cell communication, membrane trafficking, and morphogenesis is beginning to be understood. Analyses of the Arabidopsis genome sequence database (51% of genome) with conserved motor domains of kinesin and myosin families indicates the presence of a large number (about 40) of molecular motors and the functions of many of these motors remain to be discovered. It is likely that many more motors with novel regulatory
Khan, Shoukat H; Madhu, Vijay P; Rather, Tanveer A; Laway, Bashir A
Background/Aims Esophageal dysmotility is associated with gastrointestinal dysmotility in various systemic and neuroregulatory disorders. Hypothyroidism has been reported to be associated with impaired motor function in esophagus due to accumulation of glycosaminoglycan hyaluronic acid in its soft tissues, leading to changes in various contraction and relaxation parameters of esophagus, particularly in the lower esophageal sphincter. In this study we evaluated esophageal transit times in patients of primary hypothyroidism using the technique of radionuclide esophageal transit scintigraphy. Methods Thirty-one patients of primary hypothyroidism and 15 euthyroid healthy controls were evaluated for esophageal transit time using 15–20 MBq of Technetium-99m sulfur colloid diluted in 10–15 mL of drinking water. Time activity curve was generated for each study and esophageal transit time was calculated as time taken for clearance of 90% radioactive bolus from the region of interest encompassing the esophagus. Esophageal transit time of more than 10 seconds was considered as prolonged. Results Patients of primary hypothyroidism had a significantly increased mean esophageal transit time of 19.35 ± 20.02 seconds in comparison to the mean time of 8.25 ± 1.71 seconds in healthy controls (P < 0.05). Esophageal transit time improved and in some patients even normalized after treatment with thyroxine. A positive correlation (r = 0.39, P < 0.05) albeit weak existed between the serum thyroid stimulating hormone and the observed esophageal transit time. Conclusions A significant number of patients with primary hypothyroidism may have subclinical esophageal dysmotility with prolonged esophageal transit time which can be reversible by thyroxine treatment. Prolonged esophageal transit time in primary hypothyroidism may correlate with serum thyroid stimulating hormone levels. PMID:27444283
Mearin, Fermín; Rey, Enrique; Balboa, Agustín
This article discusses the most interesting studies on functional and motor gastrointestinal disorders presented at Digestive Diseases Week (DDW), 2015. Researchers are still seeking biomarkers for irritable bowel syndrome and have presented new data. One study confirmed that the use of low-dose antidepressants has an antinociceptive effect without altering the psychological features of patients with functional dyspepsia. A contribution that could have immediate application is the use of transcutaneous electroacupuncture, which has demonstrated effectiveness in controlling nausea in patients with gastroparesis. New data have come to light on the importance of diet in irritable bowel syndrome, although the effectiveness of a low-FODMAP diet seems to be losing momentum with time. Multiple data were presented on the long-term efficacy of rifaximin therapy in patients with irritable bowel syndrome and diarrhoea. In addition, among other contributions, and more as a curiosity, a study evaluated the effect of histamine in the diet of patients with irritable bowel syndrome.
Pouderoux, P; Kahrilas, P J
This study investigated deglutitive axial force developed within the pharynx, upper esophageal sphincter (UES), and cervical esophagus. Position and deglutitive excursion of the UES were determined using combined manometry and videofluoroscopy in eight healthy volunteers. Deglutitive clearing force was quantified with a force transducer to which nylon balls of 6- or 8-mm diameter were tethered and positioned within the oropharynx, hypopharynx, UES, and cervical esophagus. Axial force recordings were synchronized with videofluoroscopic imaging. Clearing force was dependent on both sphere diameter (P < 0.05) and location, with greater force exhibited in the hypopharynx and UES compared with the oropharynx and esophagus (P < 0.05). Within the UES, the onset of traction force coincided with passage of the pharyngeal clearing wave but persisted well beyond this. On videofluoroscopy, the persistent force was associated with the aboral motion of the ball caught within the UES. Force abated with gradual slippage of the UES around the ball. The force attributable to the combination of UES contraction and laryngeal descent was named the grabbing effect. The grabbing effect functions to transfer luminal contents distal to the laryngeal inlet at the end of the pharyngeal swallow, presumably acting to prevent regurgitation and/or aspiration of swallowed material.
Rayyan, Maissa; Allegaert, Karel; Omari, Taher; Rommel, Nathalie
Dysphagia or swallowing disorder is very common (range, 15-52%) in patients with esophageal atresia. Children present with a wide range of symptoms. The most common diagnostic tools to evaluate esophageal dysphagia, such as upper barium study and manometry, aim to characterize anatomy and function of the esophageal body and the esophagogastric junction (EGJ). Using these technologies, a variety of pathological motor patterns have been identified in children with esophageal atresia. However, the most challenging part of diagnosing patients with esophageal dysphagia lies in the fact that these methods fail to link functional symptoms such as dysphagia with the esophageal motor disorders observed. A recent method, called pressure-flow analysis (PFA), uses simultaneously acquired impedance and manometry measurements, and applies an integrated analysis of these recordings to derive quantitative pressure-flow metrics. These pressure-flow metrics allow detection of the interplay between bolus flow, motor patterns, and symptomatology by combining data on bolus transit and bolus flow resistance. Based on a dichotomous categorization, flow resistance at the EGJ and ineffective esophageal bolus transit can be determined. This method has the potential to guide therapeutic decisions for esophageal dysmotility in pediatric patients with esophageal atresia.
Mearin, Fermín; Rey, Enrique; Balboa, Agustín
This article discusses the most interesting presentations at Digestive Disease Week, held in San Diego, in the field of functional and motor gastrointestinal disorders. One of the most important contributions was undoubtedly the presentation of the new Rome IV diagnostic criteria for functional gastrointestinal disorders. We therefore devote some space in this article to explaining these new criteria in the most common functional disorders. In fact, there has already been discussion of data comparing Rome IV and Rome III criteria in the diagnosis of irritable bowel syndrome, confirming that the new criteria are somewhat more restrictive. From the physiopathological point of view, several studies have shown that the aggregation of physiopathological alterations increases symptom severity in distinct functional disorders. From the therapeutic point of view, more data were presented on the efficacy of acotiamide and its mechanisms of action in functional dyspepsia, the safety and efficacy of domperidone in patients with gastroparesis, and the efficacy of linaclotide both in irritable bowel syndrome and constipation. In irritable bowel syndrome, more data have come to light on the favourable results of a low FODMAP diet, with emphasis on its role in modifying the microbiota. Finally, long-term efficacy data were presented on the distinct treatment options in achalasia.
Meneghetti, Adam T; Tedesco, Pietro; Damani, Tanuja; Patti, Marco G
This study determines the relationship among esophageal dysmotility, esophageal acid exposure, and esophageal mucosal injury in patients with gastroesophageal reflux disease (GERD). A total of 827 patients with GERD (confirmed by ambulatory pH monitoring) were divided into three groups based on the degree of mucosal injury: group A, no esophagitis, 493 patients; group B, esophagitis grades I to III, 273 patients; and group C, Barrett's esophagus, 61 patients. As mucosal damage progressed from no esophagitis to Barrett's esophagus, there was a significant decrease in lower esophageal sphincter pressure and amplitude of peristalsis in the distal esophagus, with a subsequent increase in the number of reflux episodes in 24 hours, the number of reflux episodes longer than 5 minutes, and the reflux score. These data suggest that in patients with GERD, worsening of esophageal mucosal injury may determine progressive deterioration of esophageal motor function with impairment of acid clearance and increase of esophageal acid exposure. These findings suggest that Barrett's esophagus is an end-stage form of gastroesophageal reflux, and that if surgical therapy is performed early in the course of the disease, this cascade of events might be blocked.
Hill, L.D.; Mercer, C.D.; McCallum, R.W.; Kozarek, R.
This book integrates gastroenterology and thoracic surgery to detail the comprehensive management of esophageal disease. It describes radiologic and functional evaluation of the esophagus, endoscopy, medical and surgical treatments, and results and also covers gastroesophageal reflux disease, tumors motility, esophageal replacement, intubation, esophageal diverticula, caustic esophageal injury. It presents Dr. Hill's surgical procedures in detail.
Zhang, Hang; Yao, Li; Long, Zhiying
Motor imagery training, as an effective strategy, has been more and more applied to mental disorders rehabilitation and motor skill learning. Studies on the neural mechanism underlying motor imagery have suggested that such effectiveness may be related to the functional congruence between motor execution and motor imagery. However, as compared to the studies on motor imagery, the studies on motor imagery training are much fewer. The functional alterations associated with motor imagery training and the effectiveness of motor imagery training on motor performance improvement still needs further investigation. Using fMRI, we employed a sequential finger tapping paradigm to explore the functional alterations associated with motor imagery training in both motor execution and motor imagery task. We hypothesized through 14 consecutive days motor imagery training, the motor performance could be improved and the functional congruence between motor execution and motor imagery would be sustained form pre-training phase to post-training phase. Our results confirmed the effectiveness of motor imagery training in improving motor performance and demonstrated in both pre and post-training phases, motor imagery and motor execution consistently sustained the congruence in functional neuroanatomy, including SMA (supplementary motor cortex), PMA (premotor area); M1( primary motor cortex) and cerebellum. Moreover, for both execution and imagery tasks, a similar functional alteration was observed in fusiform through motor imagery training. These findings provided an insight into the effectiveness of motor imagery training and suggested its potential therapeutic value in motor rehabilitation.
Carlson, Dustin A.; Lin, Zhiyue; Kahrilas, Peter J.; Sternbach, Joel; Donnan, Erica N.; Friesen, Laurel; Listernick, Zoe; Mogni, Benjamin; Pandolfino, John E.
Background & Aims The functional lumen imaging probe (FLIP) could improve characterization of achalasia subtypes by detecting non-occlusive esophageal contractions not observed with standard manometry. We aimed to evaluate for esophageal contractions during volumetric distention in patients with achalasia using FLIP topography. Methods Fifty one treatment-naïve patients with achalasia, defined and sub-classified by high-resolution esophageal pressure topography, and 10 asymptomatic individuals (controls) were evaluated with the FLIP during endoscopy. During stepwise distension, simultaneous intra-bag pressures and 16 channels of cross-sectional areas were measured; data were exported to software that generated FLIP topography plots. Esophageal contractility was identified by noting periods of reduced luminal diameter. Esophageal contractions were further characterized by propagation direction, repetitiveness, and based on whether they were occluding or non-occluding. Results Esophageal contractility was detected in all 10 controls: 8/10 had repetitive, antegrade, contractions and 9/10 had occluding contractions. Contractility was detected in 27% (4/15) of patients with type I achalasia and 65% (18/26, including 9 with occluding contractions) of patients with type II achalasia. Contractility was detected in all 10 patients with type III achalasia; 8 of these patients had a pattern of contractility not observed in controls (repetitive, retrograde contractions). Conclusions Esophageal contractility not observed with manometry can be detected in patients with achalasia using FLIP topography. The presence and patterns of contractility detected with FLIP topography may represent variations in pathophysiology, such as mechanisms of pan-esophageal pressurization in patients with type II achalasia. These findings could have implications for additional sub-classification to supplement prediction of the achalasia disease course. PMID:26278501
Zerbib, F; Bruley Des Varannes, S; Scarpignato, C; Leray, V; D'Amato, M; Rozé, C; Galmiche, J P
Transient lower esophageal sphincter (LES) relaxations (TLESRs) are the main underlying mechanism of gastroesophageal reflux. Although CCK acts through CCK-A receptors to increase the TLESRs induced by gastric distension, the respective roles of endogenous CCK and fundic tone in triggering postprandial TLESRs remain unknown. The aim of this study was to determine the effect of the CCK-A receptor antagonist, loxiglumide, on postprandial LES function and fundic tone in humans. LES motor events and fundic tone were simultaneously monitored in two groups of healthy volunteers. Recordings were performed during fasting and for 3 h after a liquid meal (200 ml/200 kcal) administered either orally or intraduodenally at a rate mimicking gastric emptying. Each subject received loxiglumide (10 mg. kg-1. h-1) or saline (control) in randomized order, which was started 40 min before the meal and maintained for 3 h thereafter. After the oral meal, loxiglumide significantly reduced TLESRs (P = 0.002) without significantly affecting LES pressure and fundic tone. After duodenal infusion of the meal, loxiglumide totally abolished the increase in TLESRs, reduced LES pressure fall (P < 0.02), and strongly inhibited fundic relaxation (P = 0.0001). We concluded that endogenous CCK is involved in the postprandial control of both LES function and fundic tone through activation of CCK-A receptors.
Mearin, Fermín; Perelló, Antonia; Balboa, Agustín
on their treatments, is extensive. Consequently, 2008 has been a good year in terms of the useful information gathered for physicians interested in functional GI and motor disorders.
Since Piaget, the view that motor and cognitive development are interrelated has gained wide acceptance. However, empirical research on this issue is still rare. Few studies show a correlation of performance in cognitive and motor tasks in typically developing children. More specifically, Diamond A. (2000) hypothesizes an involvement of executive…
Riehl, M E; Pandolfino, J E; Palsson, O S; Keefer, L
Functional heartburn (FH) is a benign but burdensome condition characterized by painful, burning epigastric sensations in the absence of acid reflux or symptom-reflux correlation. Esophageal hypersensitivity and its psychological counterpart, esophageal hypervigilance (EHv) drive symptom experience. Hypnotherapy (HYP) is an established and preferred intervention for refractory symptoms in functional gastrointestinal disorders (FGIDs) and could be applied to FH. The objective of this study was to determine the feasibility, acceptability, and clinical utility of 7 weekly sessions of esophageal-directed HYP (EHYP) on heartburn symptoms, quality of life, and EHv. Similar to other work in FGIDs and regardless of hypnotizability, there were consistent and significant changes in heartburn symptoms, visceral anxiety, and quality of life and a trend for improvement in catastrophizing. We would recommend EHYP in FH patients who are either non-responsive to medications or who would prefer a lifestyle intervention.
Kahrilas PJ, Pandolfino JE. Esophageal neuromuscular function and motility disorders. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease . 9th ed. Philadelphia, PA: ...
Siwiec, Robert M.; Babaei, Arash; Kern, Mark; Samuel, Erica A.; Li, Shi-Jiang; Shaker, Reza
Background The insula plays a significant role in the interoceptive processing of visceral stimuli. We have previously shown that GERD patients have increased insular cortex activity during esophageal stimulation, suggesting a sensitized esophago-cortical neuraxis. However, information regarding the functional connectivity (FC) of the insula during visceral stimulation is lacking. The primary aim of this study was to investigate the FC of insular subregions during esophageal acid stimulation. Methods Functional imaging data was obtained from 12 GERD patients and 14 healthy subjects during four steady state conditions: (1) presence of transnasal esophageal catheter (pre-infusion); (2) neutral solution; (3) acid infusion; (4) presence of transnasal esophageal catheter following infusions (post-infusion). The insula was parcellated into 6 regions of interest (ROI). FC maps between each insular ROI and interoceptive regions were created. Differences in FC between GERD patients and healthy subjects were determined across the 4 study conditions. Key Results All GERD patients experienced heartburn during and after esophageal acidification. Significant differences between GERD patients and healthy subjects were seen in: (1) insula-thalamic FC (neutral solution infusion, acid infusion, post-infusion); (2) insula-amygdala FC (acid infusion, post-infusion); (3) insula-hippocampus and insula-cingulate FC (post-infusion). Conclusions & Inferences Esophageal stimulation in GERD patients revealed significant insular cortex FC differences with regions involved in viscerosensation and interoception. The results of our study provide further evidence that the insula, located at the transition of afferent physiologic information to human feelings, is essential for both visceral homeostasis and the experience of heartburn in GERD patients. PMID:25367277
Freede, Margaret; Leasure, A Renee; Proskin, Howard M; Hatch, Daniel; Edwards, Karethy; Pascucci, MaryAnn; Smith, Patsy R
This study tested the primary hypothesis that there is a correlation of maximum pain threshold (MPT) in the esophagus and rectum in persons with functional heartburn. Secondary aims evaluated correlations with initial perception threshold (IPT) and pain threshold (PT). This study explored objective sensory endpoints of IPT, PT, and MPT in the esophagus and rectum of 14 females with functional heartburn to determine whether visceral hypersensitivity is generalized or organ-specific. Data on volume and pressure measurements at IPT, PT, and MPT with esophageal and rectal barostat distention were collected. The relationship of sensation and pain to volume, pressure, and compliance was analyzed. Esophageal and rectal IPT balloon volume scores were highly and significantly correlated (r = .61, p = .02). Esophageal and rectal PT balloon volume scores were highly and significantly correlated (r = .6, p = .02). Esophageal and rectal MPT balloon volume scores were not correlated (r = .35, p = .26). The correlation of visceral sensitivity in the esophagus and rectum in persons with functional heartburn supports the hypothesis that visceral sensory changes in functional gastrointestinal disorders are not organ specific.
Hosoda, Moe; Furuya, Shinichi
Skilled individuals are characterized by fine-tuned perceptual and motor functions. Here, we tested the idea that the sensory and motor functions of highly-trained individuals are coupled. We assessed the relationships among multifaceted somatosensory and motor functions of expert pianists. The results demonstrated a positive covariation between the acuity of weight discrimination and the precision of force control during piano keystrokes among the pianists but not among the non-musicians. However, neither the age of starting musical training nor the total amount of life-long piano practice was correlated with these sensory-motor functions in the pianists. Furthermore, a difference between the pianists and non-musicians was absent for the weight discrimination acuity but present for precise force control during keystrokes. The results suggest that individuals with innately superior sensory function had finer motor control only in a case of having undergone musical training. Intriguingly, the tactile spatial acuity of the fingertip was superior in the pianists compared with the non-musicians but was not correlated with any functions representing fine motor control among the pianists. The findings implicate the presence of two distinct mechanisms of sensorimotor learning elicited by musical training, which occur either independently in individual sensorimotor modalities or through interacting between modalities. PMID:27886250
Wei, Gaoxia; Luo, Jing
Numerous studies provide evidence that motor skill acquisition is associated with dynamic changes in cortical and subcortical regions. Athletes are a professional population who are engaged in extensive motor training for long periods. However, the neural substrates of extreme level motor performance have not been clarified. We used kinesthetic imagery task to induce the mental representation of sport expert's extraordinary performance in view of the shared substrates of executing movement and motor imagery. For the first time, we compared, through functional magnetic resonance imaging (fMRI), the pattern of cerebral activations in 12 professional divers and 12 normal people without extensive training, during imagery of professional skills and imagery of simple motor skills. The sport experts showed significant activation in the parahippocampus during imagery of professional skills relative to the novices, which might reflect the representation adapted to experience-related motor tasks. No significant difference was found between experts and novices when they imagined simple motor skills. These results indicated the experts might utilize their kinesthetic imagery more efficiently than novices, but only for the activity in which they had expertise. The sport experts also demonstrated more focused activation patterns in prefrontal areas in both of imagery tasks, which may be relevant to higher order of motor control during motor imagery. Moreover, this study suggested that the brains of sport experts could be regarded as the ideal subjects to explore the relationship between cerebral plasticity and learning of complex motor skills.
Parnandi, Avinash; Wade, Eric; Mataric, Maja
We present an approach to wearable sensor-based assessment of motor function in individuals post stroke. We make use of one on-body inertial measurement unit (IMU) to automate the functional ability (FA) scoring of the Wolf Motor Function Test (WMFT). WMFT is an assessment instrument used to determine the functional motor capabilities of individuals post stroke. It is comprised of 17 tasks, 15 of which are rated according to performance time and quality of motion. We present signal processing and machine learning tools to estimate the WMFT FA scores of the 15 tasks using IMU data. We treat this as a classification problem in multidimensional feature space and use a supervised learning approach.
Brasseur, James G; Nicosia, Mark A; Pal, Anupam; Miller, Larry S
We summarize from previous works the functions of circular vs. longitudinal muscle in esophageal peristaltic bolus transport using a mix of experimental data, the conservation laws of mechanics and mathematical modeling. Whereas circular muscle tone generates radial closure pressure to create a local peristaltic closure wave, longitudinal muscle tone has two functions, one physiological with mechanical implications, and one purely mechanical. Each of these functions independently reduces the tension of individual circular muscle fibers to maintain closure as a consequence of shortening of longitudinal muscle locally coordinated with increasing circular muscle tone. The physiological function is deduced by combining basic laws of mechanics with concurrent measurements of intraluminal pressure from manometry, and changes in cross sectional muscle area from endoluminal ultrasound from which local longitudinal shortening (LLS) can be accurately obtained. The purely mechanical function of LLS was discovered from mathematical modeling of peristaltic esophageal transport with the axial wall motion generated by LLS. Physiologically, LLS concentrates circular muscle fibers where closure pressure is highest. However, the mechanical function of LLS is to reduce the level of pressure required to maintain closure. The combined physiological and mechanical consequences of LLS are to reduce circular muscle fiber tension and power by as much as 1/10 what would be required for peristalsis without the longitudinal muscle layer, a tremendous benefit that may explain the existence of longitudinal muscle fiber in the gut. We also review what is understood of the role of longitudinal muscle in esophageal emptying, reflux and pathology. PMID:17457963
Savarino, Edoardo; de Bortoli, Nicola; Bellini, Massimo; Galeazzi, Francesca; Ribolsi, Mentore; Salvador, Renato; Savarino, Vincenzo; Penagini, Roberto
Patients with esophageal symptoms potentially associated to esophageal motor disorders such as dysphagia, chest pain, heartburn and regurgitation, represent one of the most frequent reasons for referral to gastroenterological evaluation. The utility of esophageal manometry in clinical practice is: (1) to accurately define esophageal motor function, (2) to identify abnormal motor function, and (3) to establish a treatment plan based on motor abnormalities. With this in mind, in the last decade, investigations and technical advances, with the introduction of high-resolution esophageal manometry, have enhanced our understanding and management of esophageal motility disorders. The following recommendations were developed to assist physicians in the appropriate use of esophageal manometry in modern patient care. They were discussed and approved after a comprehensive review of the medical literature pertaining to manometric techniques and their recent application. This position statement created under the auspices of the Gruppo Italiano di Studio per la Motilità dell'Apparato Digerente (GISMAD), Società Italiana di Gastroenterologia ed Endoscopia Digestiva (SIGE) and Associazione Italiana Gastroenterologi ed Endoscopisti Digestivi Ospedalieri (AIGO) is intended to help clinicians in applying manometric studies in the most fruitful manner within the context of their patients with esophageal symptoms.
Sengupta, J N
contractions of the distal esophagus. This response undergoes inhibition in response to proximal distension. In addition, there is a second, nonrhythmic firing response that occurs both proximal and distal esophageal distension. This observation suggests that swallow-induced inhibition of the distal esophagus is controlled by the preganglionic motor neurons in the brain stem. Electrophysiological studies allow direct understanding of neuronal activities regulating esophageal functions. In vivo recording has an advantage for studying functional roles of the neurons in regulatory reflexes, whereas in vitro recording is useful for more accurate study of receptor pharmacology. Recordings from the central nervous system allow study of the neurotransmitters involved in neuronal function and the circuitry of different reflex mechanisms.
Chen, Huan-Wen; Du, Ming
Esophageal achalasia is due to the esophagus of neuromuscular dysfunction caused by esophageal functional disease. Its main feature is the lack of esophageal peristalsis, the lower esophageal sphincter pressure and to reduce the swallow's relaxation response. Lower esophageal muscular dissection is one of the main ways to treat esophageal achalasia. At present, the period of muscular layer under the thoracoscope esophagus dissection is one of the treatment of esophageal achalasia. Combined with our experience in minimally invasive esophageal surgery, to improved incision and operation procedure, and adopts the model of the complete period of muscular layer under the thoracoscope esophagus dissection in the treatment of esophageal achalasia.
Park, Eun-Young; Kim, Won-Ho
Physical therapy intervention for children with cerebral palsy (CP) is focused on reducing neurological impairments, improving strength, and preventing the development of secondary impairments in order to improve functional outcomes. However, relationship between motor impairments and functional outcome has not been proved definitely. This study confirmed the construct of motor impairment and performed structural equation modeling (SEM) between motor impairment, gross motor function, and functional outcomes of regarding activities of daily living in children with CP. 98 children (59 boys, 39 girls) with CP participated in this cross-sectional study. Mean age was 11 y 5 mo (SD 1 y 9 mo). The Manual Muscle Test (MMT), the Modified Ashworth Scale (MAS), range of motion (ROM) measurement, and the selective motor control (SMC) scale were used to assess motor impairments. Gross motor function and functional outcomes were measured using the Gross Motor Function Measure (GMFM) and the Functional Skills domain of the Pediatric Evaluation of Disability Inventory (PEDI) respectively. Measurement of motor impairment was consisted of strength, spasticity, ROM, and SMC. The construct of motor impairment was confirmed though an examination of a measurement model. The proposed SEM model showed good fit indices. Motor impairment effected gross motor function (β=-.0869). Gross motor function and motor impairment affected functional outcomes directly (β=0.890) and indirectly (β=-0.773) respectively. We confirmed that the construct of motor impairment consist of strength, spasticity, ROM, and SMC and it was identified through measurement model analysis. Functional outcomes are best predicted by gross motor function and motor impairments have indirect effects on functional outcomes.
Shim, Young Kwang; Kim, Nayoung; Park, Yo Han; Lee, Jong-Chan; Sung, Jihee; Choi, Yoon Jin; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Lee, Dong Ho
Background/Aims Disturbances of esophageal motility have been reported to be more frequent the aged population. However, the physiology of disturbances in esophageal motility during aging is unclear. The aim of this study was to evaluate the effects of age on esophageal motility using high-resolution esophageal impedance manometry (HRIM). Methods Esophageal motor function of 268 subjects were measured using HRIM in 3 age groups, < 40 years (Group A, n = 32), 40–65 years (Group B, n = 185), and > 65 years (Group C, n = 62). Lower esophageal sphincter (LES) and upper esophageal sphincter (UES) pressures, integrated relaxation pressure, distal contractile integral, contractile front velocity, distal latency, and pressures and duration of contraction on 4 positions along the esophagus, and complete bolus transit were measured. Results Basal UES pressure was lower in Group C (P < 0.001) but there was no significant difference in the LES pressure among groups. Contractile duration on position 3 (10 cm from proximal LES high pressure zone) was longer in Group C (P = 0.001), and the contractile amplitude on position 4 (5 cm from proximal LES high pressure zone) was lower in Group C (P = 0.005). Distal contractile integral was lower in Group C (P = 0.037). Contractile front velocity (P = 0.015) and the onset velocity (P = 0.040) was lower in Group C. There was no significant difference in impedance values. Conclusions The decrease of UES pressure, distal esophageal motility, and peristaltic velocity might be related with esophageal symptoms in the aged population. PMID:28163259
Russell, C.O.; Hill, L.D.; Holmes, E.R. III; Hull, D.A.; Gannon, R.; Pope, C.E. II
The purpose of this study was to extend existing nuclear medicine techniques for the diagnosis of esophageal motor disorders. A standard homogeneous bolus of 99mtechnetium sulfur colloid in water was swallowed in the supine position under the collimator of a gamma camera linked to a microprocessor. Bolus transit was recorded at 0.4-s intervals, and the movie obtained was used to analyze transit in an objective manner. Ten normal volunteers and 30 subjects with dysphagia not related to mechanical obstruction were studied with this technique. Radionuclide transit studies detected a higher incidence of esophageal motor abnormality than manometry or radiology in the dysphagia group. In addition a definitive description of the functional problem was possible in most cases. Radionuclide transit is a safe noninvasive test and suitable as a screening test for esophageal motor disorders.
Rivera Landa, Rogelio; Cardenas Cardenas, Eduardo; Fossion, Ruben; Pérez Zepeda, Mario Ulises
Technological advances in the last few decennia allow the monitoring of many physiological observables in a continuous way, which in physics is called a "time series". The best studied physiological time series is that of the heart rhythm, which can be derived from an electrocardiogram (ECG). Studies have shown that a healthy heart is characterized by a complex time series and high heart rate variability (HRV). In adverse conditions, the cardiac time series degenerates towards randomness (as seen in, e.g., fibrillation) or rigidity (as seen in, e.g., ageing), both corresponding to a loss of HRV as described by, e.g., Golberger et. al . Cardiac and digestive rhythms are regulated by the autonomous nervous system (ANS), that consists of two antagonistic branches, the orthosympathetic branch (ONS) that accelerates the cardiac rhythm but decelerates the digestive system, and the parasympathetic brand (PNS) that works in the opposite way. Because of this reason, one might expect that the statistics of gastro-esophageal time series, as described by Gardner et. al. [2,3], reflects the health state of the digestive system in a similar way as HRV in the cardiac case, described by Minocha et. al. In the present project, we apply statistical methods derived from HRV analysis to time series of esophageal acidity (24h pHmetry). The study is realized on data from a large patient population from the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Our focus is on patients with functional disease (symptoms but no anatomical damage). We find that traditional statistical approaches (e.g. Fourier spectral analysis) are unable to distinguish between different degenerations of the digestive system, such as gastric esophageal reflux disease (GERD) or functional gastrointestinal disorder (FGID).
O'Connor, M K; Byrne, P J; Keeling, P; Hennessy, T P
This study examines the scintigraphic transit pattern in a variety of esophageal disorders. Scintigraphy was performed with a semi solid bolus and the patient in an upright position. Condensed esophageal images were obtained from which we derived the esophageal transit time. The pattern of bolus transit was graded by the duration of transit and by the presence of hold up or retrograde motion. Scintigrams were performed in 11 volunteers and 88 patients whose esophageal function had been confirmed by conventional gastroesophageal techniques. Esophageal disorders examined included achalasia (20), scleroderma (9), esophageal carcinoma (8), Barrett esophagus (5), and reflux esophagitis (27). We also examined the effects of gastroesophageal surgery on esophageal function. Transit times distinguished grossly abnormal esophageal function from normal but did not distinguish between different esophageal disorders. Graded transit patterns were a more sensitive indicator of esophageal function and permitted some differentiation between esophageal disorders and allowed evaluation of the effects of gastroesophageal surgery.
Geevasinga, Nimeshan; Menon, Parvathi; Kiernan, Matthew C; Vucic, Steve
While task-dependent changes in motor cortical outputs have been previously reported, the issue of whether such changes are specific for complex hand tasks remains unresolved. The aim of the present study was to determine whether cortical inhibitory tone and cortical output were greater during precision grip and power grip. Motor cortex excitability was undertaken by using the transcranial magnetic stimulation threshold tracking technique in 15 healthy subjects. The motor-evoked potential (MEP) responses were recorded over the abductor pollicis brevis (APB), with the hand in the following positions: (1) rest, (2) precision grip and (3) power grip. The MEP amplitude (MEP amplitude REST 23.6 ± 3.3%; MEP amplitude PRECISION GRIP 35.2 ± 5.6%; MEP amplitude POWER GRIP 19.6 ± 3.4%, F = 2.4, P < 0.001) and stimulus-response gradient (SLOPEREST 0.06 ± 0.01; SLOPEPRCISION GRIP 0.15 ± 0.04; SLOPE POWER GRIP 0.07 ± 0.01, P < 0.05) were significantly increased during precision grip. Short interval intracortical inhibition (SICI) was significantly reduced during the precision grip (SICI REST 15.0 ± 2.3%; SICI PRECISION GRIP 9.7 ± 1.5%, SICI POWER GRIP 15.9 ± 2.7%, F = 2.6, P < 0.05). The present study suggests that changes in motor cortex excitability are specific for precision grip, with functional coupling of descending corticospinal pathways controlling thumb and finger movements potentially forming the basis of these cortical changes.
Gandhi, Neeraj J.; Katnani, Husam A.
The mammalian superior colliculus (SC) and its nonmammalian homolog, the optic tectum, constitute a major node in processing sensory information, incorporating cognitive factors, and issuing motor commands. The resulting action—to orient toward or away from a stimulus—can be accomplished as an integrated movement across oculomotor, cephalomotor, and skeletomotor effectors. The SC also participates in preserving fixation during intersaccadic intervals. This review highlights the repertoire of movements attributed to SC function and analyzes the significance of results obtained from causality-based experiments (microstimulation and inactivation). The mechanisms potentially used to decode the population activity in the SC into an appropriate movement command are also discussed. PMID:21456962
Cai, Ning; Gong, Yingxue; Chian, Kerm Sin; Chan, Vincent; Liao, Kin
Effective attachment of esophageal cells on biomaterials is one important requirement in designing engineered esophagus substitute for esophageal cancer treatment. In this study, poly(lactic acid) (PLA) was subjected to surface modification by coupling extracellular matrix (ECM) proteins on its surface to promote cell adhesion. Two typical ECM proteins, collagen type I (COL) and fibronectin (FN), were immobilized on the PLA surface with the aid of glutaraldehyde as a cross linker between aminolyzed PLA and ECM proteins. By using confocal reflectance interference contrast microscopy (C-RICM) integrating with phase contrast microscopy, the long-term adhesion dynamics of porcine esophageal fibroblasts (PEFs) on four types of surfaces (unmodified PLA, PLA-COOH, PLA-COL and PLA-FN) was investigated during 24 h of culture. It is demonstrated by C-RICM results that PEFs form strong adhesion contact on all four types of surfaces at different stages of cell seeding. Among the four surfaces, PEFs on the PLA-FN surface reach the maximum adhesion energy (9.5 x 10(-7) J m(-2)) in the shortest time (20 min) during the initial stage of cell seeding. After adhesion energy reaches the maximum value, PEFs maintain their highly deformed geometries till they reached a steady state after 20 h of culture. F-actin immunostaining results show that the evolvement of spatial organization of F-actin is tightly correlated with the formation of adhesion contact and cell spreading. Furthermore, the cell attachment ratio of PEFs on PLA in 2 h is only 26% compared with 88% on PLA-FN, 73% on PLA-COL and 36% on PLA-COOH. All the results demonstrate the effect of surface functionalization on the biophysical responses of PEFs in cell adhesion. Fibronectin-immobilized PLA demonstrates promising potential for application as an engineered esophagus substitute.
Li, C-Q; Huang, G-W; Wu, Z-Y; Xu, Y-J; Li, X-C; Xue, Y-J; Zhu, Y; Zhao, J-M; Li, M; Zhang, J; Wu, J-Y; Lei, F; Wang, Q-Y; Li, S; Zheng, C-P; Ai, B; Tang, Z-D; Feng, C-C; Liao, L-D; Wang, S-H; Shen, J-H; Liu, Y-J; Bai, X-F; He, J-Z; Cao, H-H; Wu, B-L; Wang, M-R; Lin, D-C; Koeffler, H P; Wang, L-D; Li, X; Li, E-M; Xu, L-Y
Long non-coding RNAs (lncRNAs) have a critical role in cancer initiation and progression, and thus may mediate oncogenic or tumor suppressing effects, as well as be a new class of cancer therapeutic targets. We performed high-throughput sequencing of RNA (RNA-seq) to investigate the expression level of lncRNAs and protein-coding genes in 30 esophageal samples, comprised of 15 esophageal squamous cell carcinoma (ESCC) samples and their 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE, to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. A number of known onco-lncRNA and many putative novel ones were effectively identified by URW-LPE. Importantly, we identified lncRNA625 as a novel regulator of ESCC cell proliferation, invasion and migration. ESCC patients with high lncRNA625 expression had significantly shorter survival time than those with low expression. LncRNA625 also showed specific prognostic value for patients with metastatic ESCC. Finally, we identified E1A-binding protein p300 (EP300) as a downstream executor of lncRNA625-induced transcriptional responses. These findings establish a catalog of novel cancer-associated functional lncRNAs, which will promote our understanding of lncRNA-mediated regulation in this malignancy. PMID:28194033
Cintas, Holly Lea; Parks, Rebecca; Don, Sarah; Gerber, Lynn
Content validity and reliability of the Brief Assessment of Motor Function (BAMF) Upper Extremity Gross Motor Scale (UEGMS) were evaluated in this prospective, descriptive study. The UEGMS is one of five BAMF ordinal scales designed for quick documentation of gross, fine, and oral motor skill levels. Designed to be independent of age and…
O'Rourke, R W; Deveney, C W; McConnell, D B; Wolfe, B M; Jobe, B A
The long-term effects of gastric banding on esophageal function are not well described. This report describes a 28-year-old woman who developed signs and symptoms of abnormal esophageal motility and lower esophageal sphincter hypotension after gastric banding for morbid obesity. The current literature addressing the effects of gastric banding on esophageal function in light of this case report is discussed.
Tsoukali, E; Gouvas, N; Tsiaoussis, J; Pechlivanides, G; Zervakis, N; Mantides, A; Xynos, E
Esophageal emptying assessed at the 'timed barium' esophagogram correlates well with symptomatic outcomes after pneumatic dilation for esophageal achalasia, although 30% of patients with satisfactory outcome exhibit partial improvement in emptying. The aim of the study was to investigate any correlation of esophageal emptying to symptomatic response after laparoscopic Heller's myotomy and Dor's fundoplication. 'Bread and barium' (transit time of a barium opaque bread bolus) and 'timed barium' (height of esophageal barium column 5 minutes after ingestion of 200-250 mL of barium suspension) esophagogram was used to assess esophageal emptying in 73 patients with esophageal achalasia before 1 and 5 years (31 cases) after laparoscopic myotomy and anterior fundoplication. Symptoms assessment was based to a specific score. At 1-year follow-up, excellent and good symptomatic results were obtained in 95% of the cases. Esophageal maximum diameter, esophageal transit time, and esophageal barium column were significantly correlated to each other and to symptom score postoperatively (P < 0.001). Complete and partial (<90% and 50-90% postoperative reduction in barium column, respectively) emptying was seen in 55% and 31% of patients with excellent result. Patients with a pseudodiverticulum postoperatively had a more delayed esophageal emptying than those without. Symptomatic outcome and esophageal emptying did not deteriorate at 5-year follow-up. Esophageal emptying assessed by 'barium and bread' and 'timed barium' esophagogram correlated well with symptomatic outcome after laparoscopic myotomy for esophageal achalasia. Complete symptomatic relief does not necessarily reflect complete esophageal emptying. Outcomes do not deteriorate by time. Because of wide availability, esophagogram can be applied in follow-up of postmyotomy patients in conjunction with symptomatic evaluation.
Hiroshima, Satoru; Anei, Ryogo; Murakami, Noboru; Kamada, Kyousuke
The supplementary motor area (SMA) is a key structure involved in behavioral planning and execution. Although many reports have indicated that SMA is organized somatotopically, its exact organization remains still unclear. This study aimed to functionally map SMA using functional magnetic resonance imaging (fMRI) and validate the fMRI-SMA by electrocortical stimulation (ECS) and postsurgical symptoms. Total 32 healthy volunteers and 24 patients participated in this study. Motor tasks were right and left finger tapping and language tasks included simple reading, lexical decision for presented words, and verb generating tasks. SPM8 was used to conduct individual and group analyses. In all subjects, the lexical decision task induced the greatest number of active fMRI pixels in SMA. fMRI during the language tasks showed anterior part of SMA compared to finger tapping tasks. We found an overlap spot with all different tasks in posterior part of SMA, which we termed SMA core. Six patients underwent awake craniotomy for ECS mapping for primary regions and SMA. During awake craniotomy, ECS to posterior part of SMA, which might involve the possible SMA core consistently, evoked both speech arrest and flaccid hemiparesis. The SMA mapping suggested posterior part of SMA might play more important roles in any executions, which might involve the SMA core.
Leisman, Gerry; Moustafa, Ahmed A.; Shafir, Tal
In this article, we argue that motor and cognitive processes are functionally related and most likely share a similar evolutionary history. This is supported by clinical and neural data showing that some brain regions integrate both motor and cognitive functions. In addition, we also argue that cognitive processes coincide with complex motor output. Further, we also review data that support the converse notion that motor processes can contribute to cognitive function, as found by many rehabilitation and aerobic exercise training programs. Support is provided for motor and cognitive processes possessing dynamic bidirectional influences on each other. PMID:27252937
Ramírez Mata, M; Ixtepan, L; Peña Ancira, F; de Ramírez, A F; Villalobos, J J; Campuzano, M
This presents the method to be followed for the valuation of the gastro-esophagic function in patients with sliding hiatal hernia, twenty-one patients with this diagnosis were studied through X-Rays. Besides gastric and esophagic endoscopy, a complete clinical examinations was made to compare the information obtained from the studies, with the direct measurement of the contractions of the esophagus and the lower sphincter through conventional manometric methods. The relationship between the simptoms and the clinical procedures done in the patients were observed as was the usefulness of esophagic manometry to detect not only the direct pressure of the gastro-esophagic sphincter, but also to determine the concurrent motor changes that can occur in patients which show hiatal hernia. The benefit of this studies to decide the therapeutic handling, specially surgical, is discussed.
Xiao, Qingpin; Hu, Xiaohui; Wei, Zhiyi; Tam, Kin Yip
Cells make use of molecular motors to transport small molecules, macromolecules and cellular organelles to target region to execute biological functions, which is utmost important for polarized cells, such as neurons. In particular, cytoskeleton motors play fundamental roles in neuron polarization, extension, shape and neurotransmission. Cytoskeleton motors comprise of myosin, kinesin and cytoplasmic dynein. F-actin filaments act as myosin track, while kinesin and cytoplasmic dynein move on microtubules. Cytoskeleton motors work together to build a highly polarized and regulated system in neuronal cells via different molecular mechanisms and functional regulations. This review discusses the structures and working mechanisms of the cytoskeleton motors in neurons.
Xiao, Qingpin; Hu, Xiaohui; Wei, Zhiyi; Tam, Kin Yip
Cells make use of molecular motors to transport small molecules, macromolecules and cellular organelles to target region to execute biological functions, which is utmost important for polarized cells, such as neurons. In particular, cytoskeleton motors play fundamental roles in neuron polarization, extension, shape and neurotransmission. Cytoskeleton motors comprise of myosin, kinesin and cytoplasmic dynein. F-actin filaments act as myosin track, while kinesin and cytoplasmic dynein move on microtubules. Cytoskeleton motors work together to build a highly polarized and regulated system in neuronal cells via different molecular mechanisms and functional regulations. This review discusses the structures and working mechanisms of the cytoskeleton motors in neurons. PMID:27570482
Dideriksen, Jakob L; Farina, Dario
It is commonly assumed that the orderly recruitment of motor units by size provides a functional advantage for the performance of movements compared with a random recruitment order. On the other hand, the excitability of a motor neuron depends on its size and this is intrinsically linked to its innervation number. A range of innervation numbers among motor neurons corresponds to a range of sizes and thus to a range of excitabilities ordered by size. Therefore, if the excitation drive is similar among motor neurons, the recruitment by size is inevitably due to the intrinsic properties of motor neurons and may not have arisen to meet functional demands. In this view, we tested the assumption that orderly recruitment is necessarily beneficial by determining if this type of recruitment produces optimal motor output. Using evolutionary algorithms and without any a priori assumptions, the parameters of neuromuscular models were optimized with respect to several criteria for motor performance. Interestingly, the optimized model parameters matched well known neuromuscular properties, but none of the optimization criteria determined a consistent recruitment order by size unless this was imposed by an association between motor neuron size and excitability. Further, when the association between size and excitability was imposed, the resultant model of recruitment did not improve the motor performance with respect to the absence of orderly recruitment. A consistent observation was that optimal solutions for a variety of criteria of motor performance always required a broad range of innervation numbers in the population of motor neurons, skewed towards the small values. These results indicate that orderly recruitment of motor units in itself does not provide substantial functional advantages for motor control. Rather, the reason for its near-universal presence in human movements is that motor functions are optimized by a broad range of innervation numbers. PMID:24144879
Rothenberger, Aribert; Roessner, Veit
Motor and vocal tics are the core symptom of Tourette syndrome (TS). Tic generation seems to develop throughout the known motor pathways. This review focuses on functional neuroimaging in order to check this assumption. Also it elucidates the alterations and interactions of motor networks in TS depending on different contexts and circumstances like resting state, spontaneous tic movements, suppression of tics and premonitory urges, voluntary goal-oriented movements as well as electrophysiological neuronal stimulation. In general, the primary tic generating motor network uses the basic motor pathways differently, interacts with secondary sensorimotor networks and neuronal systems of cognitive behavioural control in a merely hierarchical manner, changing during neurodevelopment. PMID:23187141
Sanaka, Madhusudhan R; Hayat, Umar; Thota, Prashanthi N; Jegadeesan, Ramprasad; Ray, Monica; Gabbard, Scott L; Wadhwa, Neha; Lopez, Rocio; Baker, Mark E; Murthy, Sudish; Raja, Siva
AIM: To assess and compare the esophageal function after peroral endoscopic myotomy (POEM) vs other conventional treatments in achalasia. METHODS: Chart review of all achalasia patients who underwent POEM, laparoscopic Heller myotomy (LHM) or pneumatic dilation (PD) at our institution between January 2012 and March 2015 was performed. Patient demographics, type of achalasia, prior treatments, pre- and post-treatment timed barium swallow (TBE) and high-resolution esophageal manometry (HREM) findings were compared between the three treatment groups. Patients who had both pre- and 2 mo post-treatment TBE or HREM were included in the final analysis. TBE parameters compared were barium column height, width and volume of barium remaining at 1 and 5 min. HREM parameters compared were basal lower esophageal sphincter (LES) pressures and LES-integrated relaxation pressures (IRP). Data are presented as mean ± SD, median [25th, 75th percentiles] or frequency (percent). Analysis of variance, Kruskal-Wallis test, Pearsons χ2 test and Fishers Exact tests were used for analysis. RESULTS: A total of 200 achalasia patients were included of which 36 underwent POEM, 22 underwent PD and 142 underwent LHM. POEM patients were older (55.4 ± 16.8 years vs 46.5 ± 15.7 years, P = 0.013) and had higher BMI than LHM (29.1 ± 5.9 kg/m2 vs 26 ± 5.1 kg/m2, P = 0.012). More number of patients in POEM and PD groups had undergone prior treatments compared to LHM group (72.2% vs 68.2% vs 44.3% respectively, P = 0.003). At 2 mo post-treatment, all TBE parameters including barium column height, width and volume remaining at 1 and 5 min improved significantly in all three treatment groups (P = 0.01 to P < 0.001) except the column height at 1 min in PD group (P = 0.11) . At 2 mo post-treatment, there was significant improvement in basal LES pressure and LES-IRP in both LHM (40.5 mmHg vs 14.5 mmHg and 24 mmHg vs 7.1 mmHg respectively, P < 0.001) and POEM groups (38.7 mmHg vs 11.4 mmHg and 23.6 mm
Schulz, Robert; Koch, Philipp; Zimerman, Maximo; Wessel, Maximilian; Bönstrup, Marlene; Thomalla, Götz; Cheng, Bastian; Gerloff, Christian; Hummel, Friedhelm C
Corticocortical interactions between the primary motor cortex, the ventral premotor cortex and posterior parietal motor areas, such as the anterior and caudal intraparietal sulcus, are relevant for skilled voluntary hand function. It remains unclear to what extent these brain regions and their interactions also contribute to basic motor functions after stroke. We hypothesized that white matter integrity of the underlying parietofrontal motor pathways between these brain regions might relate to residual motor function after stroke. Twenty-five chronic stroke patients were recruited (aged 64 ± 8.8 years, range 46-75, 17 males, one left-handed) and evaluated 34 months after stroke (range 12-169 months) by means of grip force, pinch force and the Fugl-Meyer assessment of the upper extremity. Based on these measures, motor function was estimated applying a factor analysis with principal component extraction. Using diffusion tensor imaging and probabilistic tractography we reconstructed probable intrahemispheric trajectories between the primary motor cortex, the ventral premotor cortex and the anterior and caudal intraparietal sulcus in each patient. White matter integrity was estimated for each individual tract by means of fractional anisotropy. Generalized linear modelling was used to relate tract-related fractional anisotropy to the motor function. We found that the white matter integrity of the fibre tracts connecting the ventral premotor cortex and the primary motor cortex (P < 0.001) and the anterior intraparietal sulcus and the ventral premotor cortex (P < 0.01) positively correlated with motor function. The other tracts investigated did not show a similar structure-behaviour association. Providing first structural connectivity data for parietofrontal connections in chronic stroke patients, the present results indicate that both the ventral premotor cortex and the posterior parietal cortex might play a relevant role in generating basic residual motor output after
Heider, T R; Farrell, T M; Kircher, A P; Colliver, C C; Koruda, M J; Behrns, K E
Abnormal esophageal motility is a relative contraindication to complete (360-degree) fundoplication because of a purported risk of postoperative dysphagia. Partial fundoplication, however, may be associated with increased postoperative esophageal acid exposure. Our aim was to determine if complete fundoplication is associated with increased postoperative dysphagia in patients with abnormal esophageal motor function. Medical records of 140 patients (79 females; mean age 48 +/- 1.1 years) who underwent fundoplication for gastroesophageal reflux disease (GERD) were reviewed retrospectively to document demographic data, symptoms, and diagnostic test results. Of the 126 patients who underwent complete fundoplication, 25 met manometric criteria for abnormal esophageal motility (#30 mm Hg mean distal esophageal body pressure or #80% peristalsis), 68 had normal esophageal function, and 33 had incomplete manometric data and were therefore excluded from analysis. Of the 11 patients who underwent partial fundoplication, eight met criteria for abnormal esophageal motility, two had normal esophageal function, and one had incomplete data and was therefore excluded. After a median follow-up of 2 years (range 0.5 to 5 years), patients were asked to report heartburn, difficulty swallowing, and overall satisfaction using a standardized scoring scale. Complete responses were obtained in 72%. Sixty-five patients who underwent complete fundoplication and had manometric data available responded (46 normal manometry; 19 abnormal manometry). Outcomes were compared using the Mann-Whitney U test. After complete fundoplication, similar postoperative heartburn, swallowing, and overall satisfaction were reported by patients with normal and abnormal esophageal motility. Likewise, similar outcomes were reported after partial fundoplication. This retrospective study found equally low dysphagia rates regardless of baseline esophageal motility; therefore a randomized trial comparing complete versus
Mehrkanoon, Saeid; Boonstra, Tjeerd W; Breakspear, Michael; Hinder, Mark; Summers, Jeffery J
Interactions between the cerebellum and primary motor cortex are crucial for the acquisition of new motor skills. Recent neuroimaging studies indicate that learning motor skills is associated with subsequent modulation of resting-state functional connectivity in the cerebellar and cerebral cortices. The neuronal processes underlying the motor-learning-induced plasticity are not well understood. Here, we investigate changes in functional connectivity in source-reconstructed electroencephalography (EEG) following the performance of a single session of a dynamic force task in twenty young adults. Source activity was reconstructed in 112 regions of interest (ROIs) and the functional connectivity between all ROIs was estimated using the imaginary part of coherence. Significant changes in resting-state connectivity were assessed using partial least squares (PLS). We found that subjects adapted their motor performance during the training session and showed improved accuracy but with slower movement times. A number of connections were significantly upregulated after motor training, principally involving connections within the cerebellum and between the cerebellum and motor cortex. Increased connectivity was confined to specific frequency ranges in the mu- and beta-bands. Post hoc analysis of the phase spectra of these cerebellar and cortico-cerebellar connections revealed an increased phase lag between motor cortical and cerebellar activity following motor practice. These findings show a reorganization of intrinsic cortico-cerebellar connectivity related to motor adaptation and demonstrate the potential of EEG connectivity analysis in source space to reveal the neuronal processes that underpin neural plasticity.
Del Vecchio, S; Gargiulo, P A
In the present work, visual and motor functions have been explored in 26 chronic schizophrenic patients, and 7 acute schizophrenic patients, compared with 26 normal controls, by means of the Bender-Gestalt Test. Parameters under consideration were: Form distortion, rotation, integration, perseveration, use of space, subtle motricity, score (global parameter), and time employed. As regards distortion and rotation there have been highly significant differences between chronic patients and control group. Among acute patients, it was observed that perseveration was also highly significant. Conversely, integration and use of space did not differ significantly among the three groups involved. The global score, resulting from all the above mentioned parameters showed important differences between both patient groups on the one hand, and control group on the other hand. Taking into account that patients were being administered neuroleptic drugs, it can safely be said, however, that the Bender-Gestalt Test allows to recognize alteration in perceptual closure consistent with a loss of the objective structure of perceived phenomena, in both chronic and acute patients.
Matsumoto, Hideo; Kubota, Hisako; Higashida, Masaharu; Manabe, Noriaki; Haruma, Ken; Hirai, Toshihiro
Introduction Esophageal diverticulum, a relatively rare condition, has been considered to be associated with motor abnormalities such as conditions that cause a lack of coordination between the distal esophagus and lower esophageal sphincter. Presentation of case We herein report a case of esophageal epiphrenic diverticulum associated with diffuse esophageal spasm. A 73-year-old woman presented with dysphagia and regurgitation. Imaging examinations revealed a right-sided esophageal diverticulum located about 10 cm above the esophagogastric junction. High-resolution manometry revealed normal esophageal motility. However, 24-h pH monitoring revealed continuous acidity due to pooling of residue in the diverticulum. An esophageal epiphrenic diverticulum was diagnosed and resected thoracoscopically. Her dysphagia recurred 2 years later. High-resolution manometry revealed diffuse esophageal spasm. Discussion The diverticulum in the present case was considered to have been associated with diffuse esophageal spasm. The motility disorder was likely not identified at the first evaluation. Conclusion In this case, the patient’s symptoms spontaneously resolved without any treatment; however, longer-term follow-up is needed. PMID:26143577
unlikely system for spinal cord injury: namely crustacean motor networks such as the stomatogastric ganglion (STG)6. While the STG is an invertebrate...typically modify activity by regulating the properties or expression levels of subsets of ionic channels. In the stomatogastric system of crustaceans ...conductances preserves output in a computational model of a crustacean cardiac motor neuron. J Neurosci 30: 8637–8649, 2010. Baro DJ, Levini RM, Kim MT
... from your throat to your stomach. Early esophageal cancer usually does not cause symptoms. Later, you may ... You're at greater risk for getting esophageal cancer if you smoke, drink heavily, or have acid ...
Cancer - esophagus ... Esophageal cancer is not common in the United States. It occurs most often in men over 50 years old. There are two main types of esophageal cancer: squamous cell carcinoma and adenocarcinoma. These two types ...
Tieman, Beth L.; Palisano, Robert J.; Sutlive, Ann C.
The process of identification of children with delays or disorders in motor development includes developmental screening, examination, and reexamination. Throughout this process, various types of measures are used, including discriminative and evaluative measures. Discriminative and evaluative measures of motor development and function that are…
Executive function often refers to control behaviors such as "initiating," "sustaining," "inhibiting," and "switching." These mechanisms contribute to regulation of thinking and emotion but can be observed most clearly in the motor system. Neuropsychology has been influenced by "top-down" models of cognitive control that emerged from information-processing theories of cognition. In fact, neural models provide evidence that control processes are highly interactive within the cortico-striatal-cerebellar circuits. Cognition unfolds in response to motor-driven adaptation, and evidence exists for similar firing of brain cells and circuits during "imagined action" as in actual motor behavior. The motor system develops early and yet is not routinely assessed in neuropsychological evaluation of children with neurodevelopmental disorders. This article reviews some of the approaches to motor assessment that have sensitivity to neurodevelopmental disorders, and advocates for inclusion of motor assessment, particularly in evaluating control processes independent of culture, language, and other confounders.
This article presents the elements of the Oral Motor Intervention section of the Infant Care Path for Physical Therapy in the Neonatal Intensive Care Unit (NICU). The types of physical therapy interventions presented in this path are evidence based as well as infant driven and family focused. In the context of anticipated maturation of…
Di Stefano, M; Papathanasopoulos, A; Blondeau, K; Vos, R; Boecxstaens, V; Farré, R; Rommel, N; Tack, J
There are limited data concerning the effects of 5-HT(1A) receptor activation on esophageal motility. Sumatriptan, a 5-HT(1A) receptor agonist, was recently reported to enhance esophageal peristalsis after intravenous administration. Buspirone, an orally available 5-HT(1A) receptor agonist, was shown to modulate gastroduodenal motor function. Our aim was to evaluate the effect of buspirone on esophageal motility of healthy volunteers. On two separate visits, 20 healthy volunteers aged 21-29 years (nine women) underwent esophageal manometry before and 10, 30, and 60 minutes after the administration of buspirone 20-mg or placebo capsule, according to a double-blind crossover design. At each time point, we compared buspirone and placebo effects on: resting pressure of the lower esophageal sphincter (LES); residual pressure and duration of LES relaxation; amplitude, duration, and onset velocity of esophageal body contractions, during 10 swallows of 5 mL of water. Significant analysis of variance differences (P < 0.05) are presented as mean ± standard deviation. Buspirone significantly increased mean distal esophageal wave amplitude (151 vs. 87 mmHg, P < 0.05) and duration (6.1 vs. 4.2 seconds, P < 0.05). Similarly, buspirone significantly increased mean LES resting pressure (26 vs. 21 mmHg, P < 0.05) and mean residual LES pressure (7.9 vs. 2 mmHg, P < 0.05), whereas reduced mean LES relaxation duration (7.2 vs. 8.0 seconds, P < 0.05) and mean distal onset velocity (7.6 vs. 14.7 cm/second, P < 0.05). Buspirone enhances esophageal peristalsis and LES function in healthy volunteers. Further study is warranted on the effects of buspirone on esophageal function and symptoms in patients with ineffective esophageal motility.
Dinomais, Mickael; Chinier, Eva; Richard, Isabelle; Ricalens, Emmanuel; Aubé, Christophe; N'Guyen The Tich, Sylvie; Ter Minassian, Aram
Cerebral asymmetry is a common feature of human functions. However, there are discrepancies in the literature about functional hemispheric asymmetries in the supplementary motor area (SMA), specifically in the posterior part (SMA-proper). We used resting state functional connectivity MRI to investigate the left-right asymmetries of the functional networks associated with primary motor cortex (M1) and SMA-proper using a "seed"-based correlation analysis in 30 healthy right-handed subjects. We showed that left M1 was more connected with areas involved in the motor system than right M1, and that right SMA-proper had more functional connections than its left counterpart. Our results are in agreement with a leftward asymmetry for M1 connectivity, whereas there is a rightward asymmetry of the SMA-proper connectivity.
Wang, Chuanming; Chan, John S. Y.; Ren, Lijie; Yan, Jin H.
Due to a sedentary lifestyle, more and more people are becoming obese nowadays. In addition to health-related problems, obesity can also impair cognition and motor performance. Previous results have shown that obesity mainly affects cognition and motor behaviors through altering brain functions and musculoskeletal system, respectively. Many factors, such as insulin/leptin dysregulation and inflammation, mediate the effect of obesity and cognition and motor behaviors. Substantial evidence has suggested exercise to be an effective way to improve obesity and related cognitive and motor dysfunctions. This paper aims to discuss the association of obesity with cognition and motor behaviors and its underlying mechanisms. Following this, mechanisms of exercise to improve obesity-related dysfunctions are described. Finally, implications and future research direction are raised. PMID:26881095
Monti, R. J.; Roy, R. R.; Edgerton, V. R.
Motor units, defined as a motoneuron and all of its associated muscle fibers, are the basic functional units of skeletal muscle. Their activity represents the final output of the central nervous system, and their role in motor control has been widely studied. However, there has been relatively little work focused on the mechanical significance of recruiting variable numbers of motor units during different motor tasks. This review focuses on factors ranging from molecular to macroanatomical components that influence the mechanical output of a motor unit in the context of the whole muscle. These factors range from the mechanical properties of different muscle fiber types to the unique morphology of the muscle fibers constituting a motor unit of a given type and to the arrangement of those motor unit fibers in three dimensions within the muscle. We suggest that as a result of the integration of multiple levels of structural and physiological levels of organization, unique mechanical properties of motor units are likely to emerge. Copyright 2001 John Wiley & Sons, Inc.
Stray, Liv Larsen; Stray, Torstein; Iversen, Synnøve; Ruud, Anne; Ellertsen, Bjørn
Background A previous study showed that a high percentage of children diagnosed with Hyperkinetic Disorder (HKD) displayed a consistent pattern of motor function problems. The purpose of this study was to investigate the effect of methylphenidate (MPH) on such motor performance in children with HKD Methods 25 drug-naïve boys, aged 8–12 yr with a HKD-F90.0 diagnosis, were randomly assigned into two groups within a double blind cross-over design, and tested with a motor assessment instrument, during MPH and placebo conditions. Results The percentage of MFNU scores in the sample indicating 'severe motor problems' ranged from 44–84%, typically over 60%. Highly significant improvements in motor performance were observed with MPH compared to baseline ratings on all the 17 subtests of the MFNU 1–2 hr after administration of MPH. There were no significant placebo effects. The motor improvement was consistent with improvement of clinical symptoms. Conclusion The study confirmed our prior clinical observations showing that children with ADHD typically demonstrate marked improvements of motor functions after a single dose of 10 mg MPH. The most pronounced positive MPH response was seen in subtests measuring either neuromotor inhibition, or heightened muscular tone in the gross movement muscles involved in maintaining the alignment and balance of the body. Introduction of MPH generally led to improved balance and a generally more coordinated and controlled body movement. PMID:19439096
Carmel, Jason B; Martin, John H
The corticospinal system-with its direct spinal pathway, the corticospinal tract (CST) - is the primary system for controlling voluntary movement. Our approach to CST repair after injury in mature animals was informed by our finding that activity drives establishment of connections with spinal cord circuits during postnatal development. After incomplete injury in maturity, spared CST circuits sprout, and partially restore lost function. Our approach harnesses activity to augment this injury-dependent CST sprouting and to promote function. Lesion of the medullary pyramid unilaterally eliminates all CST axons from one hemisphere and allows examination of CST sprouting from the unaffected hemisphere. We discovered that 10 days of electrical stimulation of either the spared CST or motor cortex induces CST axon sprouting that partially reconstructs the lost CST. Stimulation also leads to sprouting of the cortical projection to the magnocellular red nucleus, where the rubrospinal tract originates. Coordinated outgrowth of the CST and cortical projections to the red nucleus could support partial re-establishment of motor systems connections to the denervated spinal motor circuits. Stimulation restores skilled motor function in our animal model. Lesioned animals have a persistent forelimb deficit contralateral to pyramidotomy in the horizontal ladder task. Rats that received motor cortex stimulation either after acute or chronic injury showed a significant functional improvement that brought error rate to pre-lesion control levels. Reversible inactivation of the stimulated motor cortex reinstated the impairment demonstrating the importance of the stimulated system to recovery. Motor cortex electrical stimulation is an effective approach to promote spouting of spared CST axons. By optimizing activity-dependent sprouting in animals, we could have an approach that can be translated to the human for evaluation with minimal delay.
McGregor, Heather R; Cashaback, Joshua G A; Gribble, Paul L
An influential idea in neuroscience is that the sensory-motor system is activated when observing the actions of others [1, 2]. This idea has recently been extended to motor learning, in which observation results in sensory-motor plasticity and behavioral changes in both motor and somatosensory domains [3-9]. However, it is unclear how the brain maps visual information onto motor circuits for learning. Here we test the idea that the somatosensory system, and specifically primary somatosensory cortex (S1), plays a role in motor learning by observing. In experiment 1, we applied stimulation to the median nerve to occupy the somatosensory system with unrelated inputs while participants observed a tutor learning to reach in a force field. Stimulation disrupted motor learning by observing in a limb-specific manner. Stimulation delivered to the right arm (the same arm used by the tutor) disrupted learning, whereas left arm stimulation did not. This is consistent with the idea that a somatosensory representation of the observed effector must be available during observation for learning to occur. In experiment 2, we assessed S1 cortical processing before and after observation by measuring somatosensory evoked potentials (SEPs) associated with median nerve stimulation. SEP amplitudes increased only for participants who observed learning. Moreover, SEPs increased more for participants who exhibited greater motor learning following observation. Taken together, these findings support the idea that motor learning by observing relies on functional plasticity in S1. We propose that visual signals about the movements of others are mapped onto motor circuits for learning via the somatosensory system.
... conditions that suppress or weaken your immune system Organisms (germs) that cause esophagitis include fungi, yeast, and viruses. Common organisms include: Candida albicans Cytomegalovirus (CMV) Herpes simplex virus ( ...
Shortsleeve, M.J.; Gauvin, G.P.; Gardner, R.C.; Greenberg, M.S.
Four patients with herpetic esophagitis were examined. In three of them, the presenting symptom was odynophagia. Early in the course of herpetic esophagitis, shallow round and oval ulcers were seen on barium esophagograms. Later, the ulcers filled with fibrinous exudate, forming nodular plaques that projected into the esophageal lumen. Although these findings are diagnostic of esophagitis, they are not specific for a herpes virus infection. The definitive diagnosis must be established by histologic examination, which demonstrates the cytopathic effect of the herpes virus infection within the squamous epithelium.
Lackner, J. R.; DiZio, P.
Microgravity provides unique, though experimentally challenging, opportunities to study motor control. A traditional research focus has been the effects of linear acceleration on vestibular responses to angular acceleration. Evidence is accumulating that the high-frequency vestibulo-ocular reflex (VOR) is not affected by transitions from a 1 g linear force field to microgravity (<1 g); however, it appears that the three-dimensional organization of the VOR is dependent on gravitoinertial force levels. Some of the observed effects of microgravity on head and arm movement control appear to depend on the previously undetected inputs of cervical and brachial proprioception, which change almost immediately in response to alterations in background force levels. Recent studies of post-flight disturbances of posture and locomotion are revealing sensorimotor mechanisms that adjust over periods ranging from hours to weeks.
Shen, Xiao-Yan; Du, Wei; Huang, Wei; Chen, Yi
Rebuilding the damaged motor function caused by spinal cord injury is one of the most serious challenges in clinical neuroscience. The function of the neural pathway under the damaged sites can be rebuilt using functional electrical stimulation technology. In this study, the locations of motor function sites in the lumbosacral spinal cord were determined with functional electrical stimulation technology. A three-dimensional map of the lumbosacral spinal cord comprising the relationship between the motor function sites and the corresponding muscle was drawn. Based on the individual experimental parameters and normalized coordinates of the motor function sites, the motor function sites that control a certain muscle were calculated. Phasing pulse sequences were delivered to the determined motor function sites in the spinal cord and hip extension, hip flexion, ankle plantarflexion, and ankle dorsiflexion movements were successfully achieved. The results show that the map of the spinal cord motor function sites was valid. This map can provide guidance for the selection of electrical stimulation sites during the rebuilding of motor function after spinal cord injury.
Shen, Xiao-yan; Du, Wei; Huang, Wei; Chen, Yi
Rebuilding the damaged motor function caused by spinal cord injury is one of the most serious challenges in clinical neuroscience. The function of the neural pathway under the damaged sites can be rebuilt using functional electrical stimulation technology. In this study, the locations of motor function sites in the lumbosacral spinal cord were determined with functional electrical stimulation technology. A three-dimensional map of the lumbosacral spinal cord comprising the relationship between the motor function sites and the corresponding muscle was drawn. Based on the individual experimental parameters and normalized coordinates of the motor function sites, the motor function sites that control a certain muscle were calculated. Phasing pulse sequences were delivered to the determined motor function sites in the spinal cord and hip extension, hip flexion, ankle plantarflexion, and ankle dorsiflexion movements were successfully achieved. The results show that the map of the spinal cord motor function sites was valid. This map can provide guidance for the selection of electrical stimulation sites during the rebuilding of motor function after spinal cord injury. PMID:27651782
Seijffers, Rhona; Zhang, Jiangwen; Matthews, Jonathan C; Chen, Adam; Tamrazian, Eric; Babaniyi, Olusegun; Selig, Martin; Hynynen, Meri; Woolf, Clifford J; Brown, Robert H
ALS is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons and atrophy of distal axon terminals in muscle, resulting in loss of motor function. Motor end plates denervated by axonal retraction of dying motor neurons are partially reinnervated by remaining viable motor neurons; however, this axonal sprouting is insufficient to compensate for motor neuron loss. Activating transcription factor 3 (ATF3) promotes neuronal survival and axonal growth. Here, we reveal that forced expression of ATF3 in motor neurons of transgenic SOD1(G93A) ALS mice delays neuromuscular junction denervation by inducing axonal sprouting and enhancing motor neuron viability. Maintenance of neuromuscular junction innervation during the course of the disease in ATF3/SOD1(G93A) mice is associated with a substantial delay in muscle atrophy and improved motor performance. Although disease onset and mortality are delayed, disease duration is not affected. This study shows that adaptive axonal growth-promoting mechanisms can substantially improve motor function in ALS and importantly, that augmenting viability of the motor neuron soma and maintaining functional neuromuscular junction connections are both essential elements in therapy for motor neuron disease in the SOD1(G93A) mice. Accordingly, effective protection of optimal motor neuron function requires restitution of multiple dysregulated cellular pathways.
[Purpose] The purpose of this study was to determine effects of Gross Motor Function Classification System and Manual Ability Classification System levels on performance-based motor skills of children with spastic cerebral palsy. [Subjects and Methods] Twenty-three children with cerebral palsy were included. The Assessment of Motor and Process Skills was used to evaluate performance-based motor skills in daily life. Gross motor function was assessed using Gross Motor Function Classification Systems, and manual function was measured using the Manual Ability Classification System. [Results] Motor skills in daily activities were significantly different on Gross Motor Function Classification System level and Manual Ability Classification System level. According to the results of multiple regression analysis, children categorized as Gross Motor Function Classification System level III scored lower in terms of performance based motor skills than Gross Motor Function Classification System level I children. Also, when analyzed with respect to Manual Ability Classification System level, level II was lower than level I, and level III was lower than level II in terms of performance based motor skills. [Conclusion] The results of this study indicate that performance-based motor skills differ among children categorized based on Gross Motor Function Classification System and Manual Ability Classification System levels of cerebral palsy. PMID:28265171
[Purpose] The purpose of this study was to determine effects of Gross Motor Function Classification System and Manual Ability Classification System levels on performance-based motor skills of children with spastic cerebral palsy. [Subjects and Methods] Twenty-three children with cerebral palsy were included. The Assessment of Motor and Process Skills was used to evaluate performance-based motor skills in daily life. Gross motor function was assessed using Gross Motor Function Classification Systems, and manual function was measured using the Manual Ability Classification System. [Results] Motor skills in daily activities were significantly different on Gross Motor Function Classification System level and Manual Ability Classification System level. According to the results of multiple regression analysis, children categorized as Gross Motor Function Classification System level III scored lower in terms of performance based motor skills than Gross Motor Function Classification System level I children. Also, when analyzed with respect to Manual Ability Classification System level, level II was lower than level I, and level III was lower than level II in terms of performance based motor skills. [Conclusion] The results of this study indicate that performance-based motor skills differ among children categorized based on Gross Motor Function Classification System and Manual Ability Classification System levels of cerebral palsy.
Vakil, Nimish; Affi, Aboud
Despite advances in our knowledge of esophageal cancer, 50% of patients present with incurable disease, and the overall survival after diagnosis is poor. The incidence of esophageal adenocarcinoma of the distal esophagus is rising at a rapid rate in developed countries. Recent advances in the epidemiology of esophageal cancer offer insights into preventive strategies in patients who are at risk. New developments in diagnosis may help detect the disease at an early stage. New diagnostic modalities permit more accurate staging procedures and allow appropriate selection of therapy. New studies provide more information on multimodality therapy for esophageal cancer, and new endoscopic techniques allow resection of small lesions without surgery. New stent designs provide better palliation by providing tumor ingrowth. These developments in the treatment of esophageal cancer are the focus of this review.
Park, Eun-Young; Kim, Won-Ho
Physical therapy intervention for children with cerebral palsy (CP) is focused on reducing neurological impairments, improving strength, and preventing the development of secondary impairments in order to improve functional outcomes. However, relationship between motor impairments and functional outcome has not been proved definitely. This study…
Bavelas, Janet Beavin; And Others
Proposes that motor mimicry functions as a nonverbal, analogic, relationship message about similarity between observer and other, and that this message is encoded according to Gestalt principles of form. Concludes that the primary function of motor mimicry must be communicative and that any relationship to vicarious processes is secondary. (RAE)
Klimkeit, Ester I; Mattingley, Jason B; Sheppard, Dianne M; Lee, Paul; Bradshaw, John L
Attention and executive functions were investigated in medicated and unmedicated children with ADHD combined type using a novel selective reaching task. This task involved responding as rapidly as possible to a target while at times having to ignore a distractor. Results indicated that unmedicated children with ADHD showed slow and inaccurate responding. Slow responding reflected problems at the stage of movement preparation but not movement execution. An attentional impairment, rather than a motor planning problem per se, appeared to underlie the slow movement preparation. Inaccurate responding reflected problems with response inhibition and selective attention, impulsivity, set-shifting, and difficulties in maintaining vigilance. Although medicated children with ADHD did not show slow movement preparation, they did show some response inaccuracy, resulting especially from impulsive responding. These findings suggest that ADHD is characterized by slow motor preparation (but not motor execution), and deficits in selective attention, vigilance, and executive functions. Preliminary results suggest that stimulant medication may resolve some of these motor, attentional and executive function deficits.
Meyer, G W; Castell, D O
Normal persons often note chest or back pain during rapid ingestion of cold liquids, commonly believed to result from cold-induced "spasm" of esophageal muscle. We studied the effects of swallowing cold liquids on esophageal function in five normal subjects, aged 20 to 44 years, by comparing their response to cold ice cream (-5 degrees C) and room temperature ice cream mix (20 degrees C). Decreased peristaltic amplitude was seen during cold ice cream ingestion, primarily in the midesophagus. When seven subjects rapidly ingested ice cream until chest pain was produced and maintained for at least 60 s, complete absence of motor activity in the distal esophagus occurred, with slow return to normal during the ensuing five minutes. Our studies indicate that ingestion of cold liquids significantly depresses peristaltic amplitudes and frequency of peristalsis in normal persons, and pain is associated with complete absence of motor activity in the body of the esophagus, rather than esophageal "spasm" as commonly believed.
Davidson, R M; Mohl, N D
The subject of pain is intimately related to that of mandibular function. It is now clear that certain types of temporomandibular disorders, particularly myofascial pain dysfunction, result, in part, from rhythmic muscle activity produced by parafunctional oral habits such as diurnal or nocturnal bruxism. Furthermore, in addition to phasic hyperactivity, evidence also suggests that masticatory muscles of patients with MPD are tonically hyperactive. The pain associated with such hyperactive musculature prompts many patients to seek professional help. This article provides an updated historical review of one important aspect of mandibular function and gives insight into the general "state of the art."
Yang, Yizeng; Katz, Jonathan P.
ABSTRACT The transcriptional regulator Krüppel-like factor 4 (KLF4) is decreased in human esophageal squamous cell cancer (ESCC), and Klf4 deletion in mice produces squamous cell dysplasia. Nonetheless the mechanisms of KLF4 downregulation in ESCC and the functions of KLF4 during ESCC development and progression are not well understood. Here, we sought to define the regulation of KLF4 and delineate the stage-specific effects of KLF4 in ESCC. We found that KLF4 expression was decreased in human ESCC and in 8 of 9 human ESCC cell lines. However, by genomic sequencing, we observed no KLF4 mutations or copy number changes in any of 52 human ESCC, suggesting other mechanisms for KLF4 silencing. In fact, KLF4 expression in human ESCC cell lines was increased by the DNA methylation inhibitor 5-azacytidine, suggesting an epigenetic mechanism for KLF4 silencing. Surprisingly, while KLF4 decreased in high-grade dysplasia and early stage tumors, KLF4 increased with advanced cancer stage, and KLF4 expression in ESCC was inversely correlated with survival. Interestingly, KLF4 promoted invasion of human ESCC cells, providing a functional link to the stage-specific expression of KLF4. Taken together, these findings suggest that KLF4 loss is necessary for esophageal tumorigenesis but that restored KLF4 expression in ESCC promotes tumor spread. Thus, the use of KLF4 as a diagnostic and therapeutic target in cancer requires careful consideration of context. PMID:26934576
Yang, Yizeng; Katz, Jonathan P
The transcriptional regulator Krüppel-like factor 4 (KLF4) is decreased in human esophageal squamous cell cancer (ESCC), and Klf4 deletion in mice produces squamous cell dysplasia. Nonetheless the mechanisms of KLF4 downregulation in ESCC and the functions of KLF4 during ESCC development and progression are not well understood. Here, we sought to define the regulation of KLF4 and delineate the stage-specific effects of KLF4 in ESCC. We found that KLF4 expression was decreased in human ESCC and in 8 of 9 human ESCC cell lines. However, by genomic sequencing, we observed no KLF4 mutations or copy number changes in any of 52 human ESCC, suggesting other mechanisms for KLF4 silencing. In fact, KLF4 expression in human ESCC cell lines was increased by the DNA methylation inhibitor 5-azacytidine, suggesting an epigenetic mechanism for KLF4 silencing. Surprisingly, while KLF4 decreased in high-grade dysplasia and early stage tumors, KLF4 increased with advanced cancer stage, and KLF4 expression in ESCC was inversely correlated with survival. Interestingly, KLF4 promoted invasion of human ESCC cells, providing a functional link to the stage-specific expression of KLF4. Taken together, these findings suggest that KLF4 loss is necessary for esophageal tumorigenesis but that restored KLF4 expression in ESCC promotes tumor spread. Thus, the use of KLF4 as a diagnostic and therapeutic target in cancer requires careful consideration of context.
Borg, Rebecca; Cauchi, Ruben J.
Membership of the survival motor neuron (SMN) complex extends to nine factors, including the SMN protein, the product of the spinal muscular atrophy (SMA) disease gene, Gemins 2–8 and Unrip. The best-characterised function of this macromolecular machine is the assembly of the Sm-class of uridine-rich small nuclear ribonucleoprotein (snRNP) particles and each SMN complex member has a key role during this process. So far, however, only little is known about the function of the individual Gemin components in vivo. Here, we make use of the Drosophila model organism to uncover loss-of-function phenotypes of Gemin2, Gemin3 and Gemin5, which together with SMN form the minimalistic fly SMN complex. We show that ectopic overexpression of the dead helicase Gem3ΔN mutant or knockdown of Gemin3 result in similar motor phenotypes, when restricted to muscle, and in combination cause lethality, hence suggesting that Gem3ΔN overexpression mimics a loss-of-function. Based on the localisation pattern of Gem3ΔN, we predict that the nucleus is the primary site of the antimorphic or dominant-negative mechanism of Gem3ΔN-mediated interference. Interestingly, phenotypes induced by human SMN overexpression in Drosophila exhibit similarities to those induced by overexpression of Gem3ΔN. Through enhanced knockdown we also uncover a requirement of Gemin2, Gemin3 and Gemin5 for viability and motor behaviour, including locomotion as well as flight, in muscle. Notably, in the case of Gemin3 and Gemin5, such function also depends on adequate levels of the respective protein in neurons. Overall, these findings lead us to speculate that absence of any one member is sufficient to arrest the SMN-Gemins complex function in a nucleocentric pathway, which is critical for motor function in vivo. PMID:24391840
To address the need for a standardized system to classify the gross motor function of children with cerebral palsy, the authors developed a five-level classification system analogous to the staging and grading systems used in medicine. Nominal group process and Delphi survey consensus methods were used to examine content validity and revise the…
Dimitriadi, Maria; Derdowski, Aaron; Kalloo, Geetika; Maginnis, Melissa S.; O’Hern, Patrick; Bliska, Bryn; Sorkaç, Altar; Nguyen, Ken C. Q.; Cook, Steven J.; Poulogiannis, George; Atwood, Walter J.; Hall, David H.; Hart, Anne C.
Spinal muscular atrophy (SMA) is caused by depletion of the ubiquitously expressed survival motor neuron (SMN) protein, with 1 in 40 Caucasians being heterozygous for a disease allele. SMN is critical for the assembly of numerous ribonucleoprotein complexes, yet it is still unclear how reduced SMN levels affect motor neuron function. Here, we examined the impact of SMN depletion in Caenorhabditis elegans and found that decreased function of the SMN ortholog SMN-1 perturbed endocytic pathways at motor neuron synapses and in other tissues. Diminished SMN-1 levels caused defects in C. elegans neuromuscular function, and smn-1 genetic interactions were consistent with an endocytic defect. Changes were observed in synaptic endocytic proteins when SMN-1 levels decreased. At the ultrastructural level, defects were observed in endosomal compartments, including significantly fewer docked synaptic vesicles. Finally, endocytosis-dependent infection by JC polyomavirus (JCPyV) was reduced in human cells with decreased SMN levels. Collectively, these results demonstrate for the first time, to our knowledge, that SMN depletion causes defects in endosomal trafficking that impair synaptic function, even in the absence of motor neuron cell death. PMID:27402754
Stewart, Jill Campbell; Dewanjee, Pritha; Tran, George; Quinlan, Erin Burke; Dodakian, Lucy; McKenzie, Alison; See, Jill; Cramer, Steven C
While the corpus callosum (CC) is important to normal sensorimotor function, its role in motor function after stroke is less well understood. This study examined the relationship between structural integrity of the motor and sensory sections of the CC, as reflected by fractional anisotropy (FA), and motor function in individuals with a range of motor impairment level due to stroke. Fifty-five individuals with chronic stroke (Fugl-Meyer motor score range 14 to 61) and 18 healthy controls underwent diffusion tensor imaging and a set of motor behavior tests. Mean FA from the motor and sensory regions of the CC and from corticospinal tract (CST) were extracted and relationships with behavioral measures evaluated. Across all participants, FA in both CC regions was significantly decreased after stroke (p < 0.001) and showed a significant, positive correlation with level of motor function. However, these relationships varied based on degree of motor impairment: in individuals with relatively less motor impairment (Fugl-Meyer motor score > 39), motor status correlated with FA in the CC but not the CST, while in individuals with relatively greater motor impairment (Fugl-Meyer motor score ≤ 39), motor status correlated with FA in the CST but not the CC. The role interhemispheric motor connections play in motor function after stroke may differ based on level of motor impairment. These findings emphasize the heterogeneity of stroke, and suggest that biomarkers and treatment approaches targeting separate subgroups may be warranted.
Stray, Liv Larsen; Stray, Torstein; Iversen, Synnøve; Ruud, Anne; Ellertsen, Bjørn; Tønnessen, Finn Egil
Background The paper presents the Motor Function Neurological Assessment (MFNU), as a tool for identifying typical motor function problems in children with Attention Deficit Hyperactivity Disorder (ADHD). The study investigated motor functions in boys diagnosed with Hyperkinetic Disorder (HKD, F.90.0). HKD corresponds to the ADHD-combined (ADHD-C) diagnosis in the DSM-IV. The paper addresses the ability of the instrument to discriminate between non-medicated boys with HKD and a control group consisting of normal non-referred boys without any clinical significant ADHD symptoms. Methods 25 drug-naïve boys, aged 8–12 years and recently diagnosed as HKD F90.0, were compared with 27 controls, all boys in the same age range, on 17 MFNU subtests, and with a 'Total score' parameter. Results On the individual subtests 80–96% (median 88%) of the ADHD group showed 'moderate' to 'severe' problems, compared to 0–44% (median 14.8%) within the control group. The percentage of 'severe problems' ranged from 44–84%, (median 64%) in the ADHD group, and 0–44% (median 0%) in the control group. The highly significant differences found between the groups on all subtests, and on the Total score scores, indicated that the MFNU had a high discriminative power when children with ADHD and normal controls were compared. The Total score parameter seemed to be a meaningful discriminator of a common underlying factor of the 17 subtests used in the study. Conclusion The study confirms our clinical findings that the MFNU measures a consistent pattern of motor function problems in children with HKD, and that these problems are rarely represented in individuals without ADHD. Further research is needed to investigate to what extent the MFNU taps motor problems that are truly specific to ADHD, in contrast to motor problems common to children with DCD or other clinical problems. PMID:19450246
Imlach, Wendy L; Beck, Erin S; Choi, Ben Jiwon; Lotti, Francesco; Pellizzoni, Livio; McCabe, Brian D
Spinal muscular atrophy (SMA) is a lethal human disease characterized by motor neuron dysfunction and muscle deterioration due to depletion of the ubiquitous survival motor neuron (SMN) protein. Drosophila SMN mutants have reduced muscle size and defective locomotion, motor rhythm, and motor neuron neurotransmission. Unexpectedly, restoration of SMN in either muscles or motor neurons did not alter these phenotypes. Instead, SMN must be expressed in proprioceptive neurons and interneurons in the motor circuit to nonautonomously correct defects in motor neurons and muscles. SMN depletion disrupts the motor system subsequent to circuit development and can be mimicked by the inhibition of motor network function. Furthermore, increasing motor circuit excitability by genetic or pharmacological inhibition of K(+) channels can correct SMN-dependent phenotypes. These results establish sensory-motor circuit dysfunction as the origin of motor system deficits in this SMA model and suggest that enhancement of motor neural network activity could ameliorate the disease.
... cancer is found, the better the chance of recovery; however, esophageal cancer is often found at an ... has decreased, the tubes will be removed. Recovery Recovery As with any surgery or operation, there are ...
Esophageal atresia (EA) is a congenital defect. This means it occurs before birth. There are several types. In most cases, the ... the lower esophagus and stomach. Most infants with EA have another defect called tracheoesophageal fistula (TEF). This ...
Dellon, Evan S.
Eosinophilic esophagitis (EoE) is a chronic immune-mediated condition where infiltration of eosinophils into the esophageal mucosa leads to symptoms of esophageal dysfunction. It has rapidly emerged as an important cause of upper GI morbidity in patients of all ages and is encountered in a substantial proportion of patients undergoing diagnostic upper endoscopy. This review discusses the clinical, endoscopic, and histologic features of EoE and presents the most recent guidelines for diagnosis of EoE. It describes selected diagnostic dilemmas including distinguishing EoE from gastroesophageal reflux disease and addressing the newly recognized clinical entity of proton pump inhibitor responsive esophageal eosinophilia. It also highlights evidence to support both pharmacologic and non-pharmacologic treatments, including topical corticosteroids, dietary elimination therapy, and endoscopic dilation. PMID:23452635
... is the sixth most common cause of cancer deaths worldwide. Incidence rates vary within different geographic locations. In some regions, higher rates of esophageal cancer cases may be attributed to tobacco and alcohol use or particular nutritional habits and ...
Culture - esophageal ... There, it is placed in a special dish (culture) and watched for the growth of bacteria, fungi, ... and Fordtran's Gastrointestinal and Liver Disease Pathophysiology/Diagnosis/Management . 10th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap ...
... its ability to move food toward the stomach ( achalasia ) A weak LES, which causes heartburn (GERD) Abnormal ... PA: Elsevier Saunders; 2010:chap 43. Read More Achalasia Esophageal spasm Gastroesophageal reflux disease Review Date 8/ ...
Luc, Guillaume; Durand, Marlène; Collet, Denis; Guillemot, Fabien; Bordenave, Laurence
Esophageal tissue engineering is still in an early state, and ideal methods have not been developed. Since the beginning of the 20th century, advances have been made in the materials that can be used to produce an esophageal substitute. Three approaches to scaffold-based tissue engineering have yielded good results. The first development concerned non-absorbable constructs based on silicone and collagen. The need to remove the silicone tube is the main disadvantage of this material. Polymeric absorbable scaffolds have been used since the 1990s. The main polymeric material used is poly (glycolic) acid combined with collagen. The problem of stenosis remains prevalent in most studies using an absorbable construct. Finally, decellularized scaffolds have been used since 2000. The promises of this new approach are unfulfilled. Indeed, stenosis occurs when the esophageal defect is circumferential regardless of the scaffold materials. Cell supplementation can decrease the rate of stenosis, but the type(s) of cells and their roles have not been defined. Finally, esophageal tissue engineering cannot provide a functional esophageal substitute, and further development is necessary prior to conducting human clinical studies.
Naro, Antonino; Bramanti, Alessia; Leo, Antonino; Manuli, Alfredo; Sciarrone, Francesca; Russo, Margherita; Bramanti, Placido; Calabrò, Rocco Salvatore
The cerebellum regulates several motor functions through two main mechanisms, the cerebellum-brain inhibition (CBI) and the motor surround inhibition (MSI). Although the exact cerebellar structures and functions involved in such processes are partially known, Purkinje cells (PC) and their surrounding interneuronal networks may play a pivotal role concerning CBI and MSI. Cerebellar transcranial alternating current stimulation (tACS) has been proven to shape specific cerebellar components in a feasible, safe, effective, and non-invasive manner. The aim of our study was to characterize the cerebellar structures and functions subtending CBI and MSI using a tACS approach. Fifteen healthy individuals underwent a cerebellar tACS protocol at 10, 50, and 300 Hz, or a sham-tACS over the right cerebellar hemisphere. We measured the tACS aftereffects on motor-evoked potential (MEP) amplitude, CBI induced by tACS (tiCBI) at different frequencies, MSI, and hand motor task performance. None of the participants had any side effect related to tACS. After 50-Hz tACS, we observed a clear tiCBI-50Hz weakening (about +30%, p < 0.001) paralleled by a MEP amplitude increase (about +30%, p = 0.001) and a reduction of the time required to complete some motor task (about -20%, p = 0.01), lasting up to 30 min. The 300-Hz tACS induced a selective, specific tiCBI-300Hz and tiCBI-50Hz modulation in surrounding muscles (about -15%, p = 0.01) and MSI potentiation (about +40%, p < 0.001). The 10-Hz tACS and the sham-tACS were ineffective (p > 0.6). Our preliminary data suggest that PC may represent the last mediator of tiCBI and that the surrounding interneuronal network may have an important role in updating MSI, tiCBI, and M1 excitability during tonic muscle contraction, by acting onto the PC. The knowledge of these neurophysiological issues offers new cues to design innovative, non-invasive neuromodulation protocols to shape cerebellar-cerebral functions.
Özçınar, Beyza; Peker, Kıvanç Derya; Demirel, Sertaç; Yanar, Fatih; Tuncer, Koray; İğci, Abdullah
Herein, a case of intramural esophageal dissection is reported and the literature is reviewed. Intramural esophageal dissection is a rare but well described condition that is characterized by a laceration between the esophageal mucosa and submucosa but without perforation. A female patient aged 86 years was hospitalized with a diagnosis of abdominal aortic aneurysm. After placement of an aortic stent, she was started on intravenous heparin. After the procedure, the patient had retching and vomiting due to sedative drugs. On the first day after the procedure, the patient experienced sudden-onset chest pain, hematemesis, back pain and odynophagia. A hematoma was detected in the thoracic esophagus, which was opened during endoscopy and began to bleed suddenly owing to air insufflation. A false lumen was visualized within the esophagus. There was no perforation. The patient was followed up conservatively and discharged from the hospital uneventfully. In conclusion, we propose that esophageal transection, a condition that is widely regarded as relatively benign in the literature, has the potential to lead to perforation. It would be expected that most cases of esophageal transection would be managed conservatively. PMID:28149126
Yuan, Y; Wang, K-N; Chen, L-Q
This review gives an overview of the esophageal anastomosis. The history, various techniques and substitution organs, their advantages and disadvantages, healing mechanism, complications, and actual trend of this essential part of esophageal surgery are described. The history of the esophageal anastomosis extending from the first anastomosis in 1901 to today has undergone more than one century. In the early days, the success rate of the anastomosis was extremely low. As the technology progressed, the anastomosis got significant achievement. Various anastomotic techniques are currently being used. However, controversies exist on the choice of anastomotic method concerning the success rate, postoperative complication and quality of life. How to choose the method, no one can give the best answer. We searched the manuscripts about the esophageal anastomoses in recent years and studied the controversy questions about the anastomosis. Performing an esophageal anastomosis is a technical matter, and suture healing is independent of the patient's biologic situation. Every anastomosis technique has its own merit, but the outcomes were different if it was performed by different surgeons, and we also found that the complication rate of the anastomosis was mainly associated with the surgeons. So the surgeons should learn from their previous experience and others to avoid technical errors.
Cairns, Kevin; Stein, Joel
We describe a patient with locked-in syndrome who had minimal volitional motor function and severe spasticity in all four extremities. The patient showed a significant improvement in volitional motor function following intrathecal baclofen pump therapy to control spasticity. This case study suggests that intrathecal baclofen pump therapy might improve motor function in select patients with locked-in syndrome.
Altermann, Caroline D. C.; Martins, Alexandre S.; Carpes, Felipe P.; Mello-Carpes, Pâmela B.
Background With aging, it is important to maintain cognitive and motor functions to ensure autonomy and quality of life. During the acquisition of motor skills, it is necessary for the elderly to understand the purpose of the proposed activities. Physical and mental practice, as well as demonstrations, are strategies used to learn movements. Objectives To investigate the influence of mental practice and the observation of movement on motor memory and to understand the relationship between cognitive function and motor performance in the execution of a sequence of digital movements in the elderly. Method This was a cross-sectional study conducted with 45 young and 45 aged subjects. The instruments used were Mini-Mental State Examination (MMSE), Manual Preference Inventory and a Digital Motor Task (composed of a training of a sequence of movements, an interval and a test phase). The subjects were divided into three subgroups: control, mental practice and observation of movement. Results The elderly depend more strongly on mental practice for the acquisition of a motor memory. In comparing the performances of people in different age groups, we found that in the elderly, there was a negative correlation between the MMSE score and the execution time as well as the number of errors in the motor task. Conclusions For the elderly, mental practice can advantage motor performance. Also, there is a significant relationship between cognitive function, learning and the execution of new motor skills. PMID:24839046
Miyazaki, Tatsuya; Sohda, Makoto; Sakai, Makoto; Tanaka, Naritaka; Suzuki, Shigemasa; Yokobori, Takehiko; Inose, Takanori; Nakajima, Masanobu; Fukuchi, Minoru; Kato, Hiroyuki; Kusano, Motoyasu; Kuwano, Hiroyuki
Esophageal motility disorders are classified primary and secondary, and primary esophageal motility disorders are classified esophageal achalasia and other diseases by manometry. An esophageal emptying disorder associated with insufficient relaxation of the lower esophageal sphincter (LES) and elimination of peristaltic waves on the esophageal body is the major abnormality of achalasia. Esophagogram, endoscopy, and manometry are used for diagnosis. As pharmacological therapy, administration of a calcium channel blocker or nitrate is useful. The pharmacological therapy is not recommended as long-term basic therapy but as a temporary treatment. At 1st, the balloon dilation method is chosen in treatment of achalasia Surgical treatment is indicated in the following cases: (1) Patients uneffected by balloon dilation, (2) Flask type with grade II to III dilation, and sigmoid type, (3) the gradual progression to the pathophysiological stage, (4) young patients, (5) complicated with esophageal cancer. Laparoscopic Heller-Dor procedure is the most popular surgical procedure, recently. It is somewhat difficult to perform surgical treatment for this functional disease. We should select the most suitable individualized treatment with efficient comprehension of the pathophysiological situation.
Gupte, Anand R; Draganov, Peter V
Eosinophilic esophagitis is increasingly recognized in adults. The diagnosis is based on the presence of both typical symptoms and pathologic findings on esophageal biopsy. Patients usually present with dysphagia, food impaction and/or reflux-like symptoms, and biopsy of the esophagus shows more than 15 eosinophils per high-power field. In addition, it is essential to exclude the presence of known causes of tissue eosinophilia such as gastroesophageal reflux disease, infections, malignancy, collagen vascular diseases, hypersensitivity, and inflammatory bowel disease. There are no standardized protocols for the therapy of eosinophilic esophagitis. A variety of therapeutic approaches including acid suppression, dietary modifications, topical corticosteroids and endoscopic dilation can be used alone or in combination. PMID:19115464
Mentis, George Z.; Blivis, Dvir; Liu, Wenfang; Drobac, Estelle; Crowder, Melissa E.; Kong, Lingling; Alvarez, Francisco J.; Sumner, Charlotte J.; O'Donovan, Michael J.
SUMMARY To define alterations of neuronal connectivity that occur during motor neuron degeneration, we characterized the function and structure of spinal circuitry in spinal muscular atrophy (SMA) model mice. SMA motor neurons show reduced proprioceptive reflexes that correlate with decreased number and function of synapses on motor neuron somata and proximal dendrites. These abnormalities occur at an early stage of disease in motor neurons innervating proximal hindlimb muscles and medial motor neurons innervating axial muscles, but only at end-stage disease in motor neurons innervating distal hindlimb muscles. Motor neuron loss follows afferent synapse loss with the same temporal and topographical pattern. Trichostatin A, which improves motor behavior and survival of SMA mice, partially restores spinal reflexes illustrating the reversibility of these synaptic defects. De-afferentation of motor neurons is an early event in SMA and may be a primary cause of motor dysfunction that is amenable to therapeutic intervention. PMID:21315257
Mentis, George Z; Blivis, Dvir; Liu, Wenfang; Drobac, Estelle; Crowder, Melissa E; Kong, Lingling; Alvarez, Francisco J; Sumner, Charlotte J; O'Donovan, Michael J
To define alterations of neuronal connectivity that occur during motor neuron degeneration, we characterized the function and structure of spinal circuitry in spinal muscular atrophy (SMA) model mice. SMA motor neurons show reduced proprioceptive reflexes that correlate with decreased number and function of synapses on motor neuron somata and proximal dendrites. These abnormalities occur at an early stage of disease in motor neurons innervating proximal hindlimb muscles and medial motor neurons innervating axial muscles, but only at end-stage disease in motor neurons innervating distal hindlimb muscles. Motor neuron loss follows afferent synapse loss with the same temporal and topographical pattern. Trichostatin A, which improves motor behavior and survival of SMA mice, partially restores spinal reflexes, illustrating the reversibility of these synaptic defects. Deafferentation of motor neurons is an early event in SMA and may be a primary cause of motor dysfunction that is amenable to therapeutic intervention.
Sisto, Fermino Fernandes; Dos Santos, Acácia Aparecida Angeli; Noronha, Ana Paula Porto
Differential Item Functioning (DIF) refers to items that do not function the same way for comparable members of different groups. The present study focuses on analyzing and classifying sex-related differential item functioning in the Bender Visual-Motor Gestalt Test. Subjects were 1,052 children attending public schools (513 boys, 539 girls, ages 6-10 years). The protocols were scored using the Bender Graduated Scoring System, which evaluates only the distortion criterion using the Rasch logistic response model. The scoring system fit the Rasch model, although two items were found to be biased by sex. When analyzing differential functioning of items for boys and girls separately, the number of differentially functioning items was equal.
Zhang, Lingli; Li, Peihong; Mao, Zhibang; Qi, Xiang; Zou, Jun; Yu, Zhusheng
Motor function changes in the unaffected hand of stroke patients with hemiplegia. These changes are often ignored by clinicians owing to the extent of motor disability of the affected hand. Finger tapping frequency and Lind-mark hand function score showed that the motor function of unaffected hands in stroke patients was poorer than that of a healthy control hand. After 2 weeks of rehabilitation treatment, motor function of the unaffected hand of stroke patients was obviously improved. Therefore, attention should also be paid to motor function in the unaffected hand of stroke patients with hemiplegia during rehabilitation. PMID:25221586
Perez, David L; Barsky, Arthur J; Daffner, Kirk; Silbersweig, David A
Although conversion disorder is closely connected to the origins of neurology and psychiatry, it remains poorly understood. In this article, the authors discuss neural and clinical parallels between lesional unawareness disorders and unilateral motor and somatosensory conversion disorder, emphasizing functional neuroimaging/disease correlates. Authors suggest that a functional-unawareness neurobiological framework, mediated by right hemisphere-lateralized, large-scale brain network dysfunction, may play a significant role in the neurobiology of conversion disorder. The perigenual anterior cingulate and the posterior parietal cortices are detailed as important in disease pathophysiology. Further investigations will refine the functional-unawareness concept, clarify the role of affective circuits, and delineate the process through which functional neurologic symptoms emerge.
Ferreira, Cláudia Lúcia Pimenta; Machado, Bárbara Cristina Zanandréa; Borges, Carina Giovana Pissinatti; Rodrigues Da Silva, Marco Antonio M; Sforza, Chiarella; De Felício, Cláudia Maria
Because temporomandibular disorders (TMDs) rehabilitation continues to be a challenge, a more comprehensive picture of the orofacial functions in patients with chronic pain is required. This study assessed the orofacial functions, including surface electromyography (EMG) of dynamic rhythmic activities, in patients with moderate-severe signs and symptoms of chronic TMD. It was hypothesized that orofacial motor control differs between patients with moderate-severe chronic TMD and healthy subjects. Seventy-six subjects (46 with TMD and 30 control) answered questionnaires of severity of TMD and chewing difficulties. Orofacial functions and EMG during chewing were assessed. Standardized EMG indices were obtained by quantitative analysis of the differential EMG signals of the paired masseter and temporal muscles, and used to describe muscular action during chewing. TMD patients showed significant greater difficulty in chewing; worse orofacial scores; longer time for free mastication; a less accurate recruitment of the muscles on the working and balancing sides, reduced symmetrical mastication index (SMI) and increased standardized activity during EMG test than healthy subjects. SMI, TMD severity and orofacial myofunctional scores were correlated (P<0.01). Impaired orofacial functions and increased activity of the muscles of balancing sides during unilateral chewing characterized the altered orofacial motor control in patients with moderate-severe chronic TMD. Implications for rehabilitation are discussed.
Woodbury, Michelle; Velozo, Craig A.; Thompson, Paul A.; Light, Kathye; Uswatte, Gitendra; Taub, Edward; Winstein, Carolee J.; Morris, David; Blanton, Sarah; Nichols-Larsen, Deborah S.; Wolf, Steven L.
Background Tools chosen to measure poststroke upper-extremity rehabilitation outcomes must match contemporary theoretical expectations of motor deficit and recovery because an assessment’s theoretical underpinning forms the conceptual basis for interpreting its score. Objective The purpose of this study was to investigate the theoretical framework of the Wolf Motor Function Test (WMFT) by (1) determining whether all items measured a single underlying trait and (2) examining the congruency between the hypothesized and the empirically determined item difficulty orders. Methods Confirmatory factor analysis (CFA) and Rasch analysis were applied to existing WMFT Functional Ability Rating Scale data from 189 participants in the EXCITE (Extremity Constraint-Induced Therapy Evaluation) trial. Fit of a 1-factor CFA model (all items) was compared with the fit of a 2-factor CFA model (factors defined according to item object-grasp requirements) with fit indices, model comparison test, and interfactor correlations. Results One item was missing sufficient data and therefore removed from analysis. CFA fit indices and the model-comparison test suggested that both models fit equally well. The 2-factor model yielded a strong interfactor correlation, and 13 of 14 items fit the Rasch model. The Rasch item difficulty order was consistent with the hypothesized item difficulty order. Conclusion The results suggest that WMFT items measure a single construct. Furthermore, the results depict an item difficulty hierarchy that may advance the theoretical discussion of the person ability versus task difficulty interaction during stroke recovery. PMID:20616302
Wuang, Y-P.; Su, C-Y.; Huang, M-H.
Background: Deficit in motor performance is common in children with intellectual disabilities (ID). A motor function measure with sound psychometric properties is indispensable for clinical and research use. The purpose of this study was to compare the psychometric properties of three commonly used clinical measures for assessing motor function in…
Rodriguez-Stanley, Sheila; Ahmed, Tanveer; Zubaidi, Sattar; Riley, Susan; Akbarali, Hamid I; Mellow, Mark H; Miner, Philip B
Chewed calcium carbonate (CaCO3) rapidly neutralizes esophageal acid and may prevent reflux, suggesting another mechanism of action independent of acid neutralization. Calcium is essential for muscle tone. Our aim was to determine if luminal calcium released from chewed antacids improved esophageal motor function in heartburn sufferers. Esophageal manometry and acid clearance (swallows and time to raise esophageal pH to 5 after a 15-ml 0.1 N HCl bolus) were performed in 18 heartburn sufferers before and after chewing two Tums EX (1500 mg CaCO3, 600 mg calcium). Subjects with hypertensive esophageal contractions or hypertensive lower esophageal sphincter pressure (LESP) were excluded. Subjects with normal to low LESP were included. Differences between parameters were determined by two-tailed paired t-tests, P < 0.05. Proximal esophageal contractile amplitude was significantly increased after CaCO3 (47.18 vs 52.97 mm Hg; P = 0.02), distal onset velocity was significantly decreased after CaCO3 (4.34 vs 3.71 cm/sec; P = 0.02), and acid clearance was significantly increased 30 min after CaCO3 (20.35 vs 11.7 swallows, [P < 0.005] and 12.19 vs 6.29 min [P < 0.007]). LESP was not altered after CaCO3 (22.70 vs 23.79 mm Hg; P = 0.551), however, LESP increased in 9 of 18 subjects. Depth of LES relaxation, medial and distal esophageal contractile amplitude, and duration of contractions were not altered by CaCO3. CaCO3 did not alter salivary secretion and pH in a subset of these subjects, and CaCO3 with secreted saliva did not neutralize a 15-ml acid bolus. The Ca2+ released after chewing of CaCO3 antacids may be partially responsible for the reduction of heartburn by significantly improving initiation of peristalsis and acid clearance.
Intercellular interactions in the nervous system are mediated by two types of dedicated structural arrangements: electrical and chemical synapses. Several characteristics distinguish these two mechanisms of communication, such as speed, reliability and the fact that electrical synapses are, potentially, bidirectional. Given these properties, electrical synapses can subserve, in addition to synchrony, three main interrelated network functions: signal amplification, noise reduction and/or coincidence detection. Specific network motifs in sensory and motor systems of invertebrates and vertebrates illustrate how signal transmission through electrical junctions contributes to a complex processing of information.
Roossien, Douglas H.; Miller, Kyle E.; Gallo, Gianluca
Dyneins are a small class of molecular motors that bind to microtubules and walk toward their minus ends. They are essential for the transport and distribution of organelles, signaling complexes and cytoskeletal elements. In addition dyneins generate forces on microtubule arrays that power the beating of cilia and flagella, cell division, migration and growth cone motility. Classical approaches to the study of dynein function in axons involve the depletion of dynein, expression of mutant/truncated forms of the motor, or interference with accessory subunits. By necessity, these approaches require prolonged time periods for the expression or manipulation of cellular dynein levels. With the discovery of the ciliobrevins, a class of cell permeable small molecule inhibitors of dynein, it is now possible to acutely disrupt dynein both globally and locally. In this review, we briefly summarize recent work using ciliobrevins to inhibit dynein and discuss the insights ciliobrevins have provided about dynein function in various cell types with a focus on neurons. We temper this with a discussion of the need for studies that will elucidate the mechanism of action of ciliobrevin and as well as the need for experiments to further analyze the specificity of ciliobreviens for dynein. Although much remains to be learned about ciliobrevins, these small molecules are proving themselves to be valuable novel tools to assess the cellular functions of dynein. PMID:26217180
Michel, Eva; Molitor, Sabine; Schneider, Wolfgang
Cognitive and motor coordination skills of children with and without motor coordination impairments were examined with a one-year follow-up investigation. Initially, children were between 4 and 6 years old. Age-appropriate tests of executive functions (updating, switching, inhibition, interference control), motor coordination (the Movement Assessment Battery for Children-2) and fitness (the Körperkoordinations-Test für Kinder) were administered in two consecutive years. Several background variables (age, socioeconomic status, medical support, clinical interventions, leisure activities) and potential moderators (nonverbal intelligence, reaction time, visual perception) were controlled. The matched sample consisted of 48 control children and 48 children with motor coordination impairments. The children's executive functions dramatically improved during the one-year period. With regard to motor coordination performance, half of the impaired children caught up to the control children's level ("remission group"), while the remaining half showed no improvement ("persisting group"). Compared to the persisting group, the children in the remission group showed markedly better interference control at both measurement points. The correlation between executive functions and motor coordination is significant in the persisting group, but not in the remission group. The results of the study are discussed in the light of the role of executive functions, especially inhibition processes, for the automatization of motor coordination tasks.
Baldassarre, Antonello; Ramsey, Lenny; Rengachary, Jennifer; Zinn, Kristi; Siegel, Joshua S; Metcalf, Nicholas V; Strube, Michael J; Snyder, Abraham Z; Corbetta, Maurizio; Shulman, Gordon L
Strokes often cause multiple behavioural deficits that are correlated at the population level. Here, we show that motor and attention deficits are selectively associated with abnormal patterns of resting state functional connectivity in the dorsal attention and motor networks. We measured attention and motor deficits in 44 right hemisphere-damaged patients with a first-time stroke at 1-2 weeks post-onset. The motor battery included tests that evaluated deficits in both upper and lower extremities. The attention battery assessed both spatial and non-spatial attention deficits. Summary measures for motor and attention deficits were identified through principal component analyses on the raw behavioural scores. Functional connectivity in structurally normal cortex was estimated based on the temporal correlation of blood oxygenation level-dependent signals measured at rest with functional magnetic resonance imaging. Any correlation between motor and attention deficits and between functional connectivity in the dorsal attention network and motor networks that might spuriously affect the relationship between each deficit and functional connectivity was statistically removed. We report a double dissociation between abnormal functional connectivity patterns and attention and motor deficits, respectively. Attention deficits were significantly more correlated with abnormal interhemispheric functional connectivity within the dorsal attention network than motor networks, while motor deficits were significantly more correlated with abnormal interhemispheric functional connectivity patterns within the motor networks than dorsal attention network. These findings indicate that functional connectivity patterns in structurally normal cortex following a stroke link abnormal physiology in brain networks to the corresponding behavioural deficits.
Herpetic esophagitis is a herpes simplex infection causing inflammation and ulcers of the esophagus. Symptoms include difficulty swallowing and pain (dysphagia). Herpetic esophagitis can be effectively ...
AMINI, Malek; ALIABADI, Faranak; ALIZADE, Mehdi; KALANI, Majid; QORBANI, Mostafa
Objective Nowadays, the evaluation of all aspects of infant development is important. However, in practice, some of these assessments, especially those requiring more manipulation on high-risk infants, may impose additional stress on them. Therefore, sometimes it is essential to utilize the results of a developmental assessment for the prediction of some other aspects of development. This study evaluated the relationship between the scores of the behavioral tests and the motor function test. Materials & Methods This cross-sectional study and was undertaken in the Neonatal Intensive Care Center and Clinic of Shahid Akbar Abadi Hospital, Tehran, Iran. A group of 50 infants with low birth weights was selected based on the easy non-contingency method and the inclusion criteria, and served as the participants. In order to assess the motor function and the behavioral performance, the motor function test (a test of infant motor performance (TIMP)) and the neonatal behavioral assessment scale (neonatal behavioral assessment scale (NBAS)) were used respectively. TIMP has both stimulation and observation sections. The items include habituation, social interaction, motor system, state organization, state regulation, autonomic system, smile, supplementary items, and the reflex. Results No significant association was found between the items of the habituation of behavioral testing and the observation of the movement test. There was no statistically significant relationship between the habituation and stimulation sections as well as between the system autonomous of the behavioral test and the observation section of the motor test (P>0.05). The relationship between other variables was statistically significant (P<0.05). Conclusion The scores of some behavioral performance items could be a good predictor of the scores of the motor function items for low birth weight infants in the neonatal period. PMID:27843466
Chase, T N; Mouradian, M M; Engber, T M
Motor response complications eventually appear in most patients with advanced Parkinson's disease being treated with levodopa. The interval between onset of parkinsonism and emergence of these adverse events appears independent of the dose or the duration of therapy. Current evidence suggests that "wearing-off" fluctuations largely reflect the loss of normally functioning dopaminergic terminals, although postsynaptic alterations contribute somewhat to the underlying decline in the duration of levodopa's antiparkinsonian action. "On-off" fluctuations and peak-dose dyskinesias, on the other hand, appear to arise mainly as a consequence of postjunctional alterations that follow exposure to nonphysiologic intrasynaptic dopamine fluctuations in patients who have lost the buffering afforded by dopaminergic terminals. Studies in rats with 6-hydroxydopamine lesions indicate that striking functional alterations occur in striatal dopaminoceptive systems as a result of dopaminergic denervation and that levodopa replacement, particularly when given intermittently, fails to normalize these changes. To the extent that similar alterations contribute to the appearance of motor complications, the successful symptomatic therapy of Parkinson's disease may require continuous dopaminergic stimulation, as well as direct pharmacologic targeting of striatal dopaminoceptive systems.
Barbeau, H; McCrea, D A; O'Donovan, M J; Rossignol, S; Grill, W M; Lemay, M A
Motivated by the challenge of improving neuroprosthetic devices, the authors review current knowledge relating to harnessing the potential of spinal neural circuits, such as reflexes and pattern generators. If such spinal interneuronal circuits could be activated, they could provide the coordinated control of many muscles that is so complex to implement with a device that aims to address each participating muscle individually. The authors' goal is to identify candidate spinal circuits and areas of research that might open opportunities to effect control of human limbs through electrical activation of such circuits. David McCrea's discussion of the ways in which hindlimb reflexes in the cat modify motor activity may help in developing optimal strategies for functional neuromuscular stimulation (FNS), by using knowledge of how reflex actions can adapt to different conditions. Michael O'Donovan's discussion of the development of rhythmogenic networks in the chick embryo may provide clues to methods of generating rhythmic activity in the adult spinal cord. Serge Rossignol examines the spinal pattern generator for locomotion in cats, its trigger mechanisms, modulation and adaptation, and suggests how this knowledge can help guide therapeutic approaches in humans. Hugues Barbeau applies the work of Rossignol and others to locomotor training in human subjects who have suffered spinal cord injury (SCI) with incomplete motor function loss (IMFL). Michel Lemay and Warren Grill discuss some of the technical challenges that must be addressed by engineers to implement a neuroprosthesis using electrical stimulation of the spinal cord, particularly the control issues that would have to be resolved.
Yue, Dongli; Fan, Qingxia; Chen, Xinfeng; Li, Feng; Wang, Liping; Huang, Lan; Dong, Wenjie; Chen, Xiaoqi; Zhang, Zhen; Liu, Jinyan; Wang, Fei; Wang, Meng; Zhang, Bin [The Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan; The Department of Hematology and others
Hepatocyte growth factor activator inhibitor type 2 (SPINT2), a Kunitz-type serine proteinase inhibitor, has been identified as a putative tumor suppressor gene silenced by promoter methylation. We aimed to investigate whether SPINT2 might act as an esophageal squamous cell carcinoma (ESCC) tumor suppressor gene. Four ESCC cell lines, Fifty-two ESCC tissues and twenty-nine neighboring non-cancerous tissues were included in this study. The expression of SPINT2 was monitored by real time PCR. Bisulfite genomic sequencing and methylation-specific PCR were used to analyze methylation status. The effect of SPINT2 on cell proliferation and apoptosis in EC109 and EC9706 cells was observed by CCK-8 assay and flow cytometric analysis. We found that silencing of SPINT2 was associated with promoter methylation in ESCC cell lines. The densely methylated SPINT2 promoter region was confirmed by bisulfite genomic sequencing. Ectopic expression of SPINT2 inhibited cell proliferation through inducing cell apoptosis in vitro. Furthermore, methylation-specific PCR analysis revealed that SPINT2 promoter methylation was prominent in carcinoma tissues (52.08%) compared with neighboring non-cancerous tissues (22.58%). Kaplan–Meier analysis showed that patients with SPINT2 hypermethylation had shorter survival time. The tumor suppressor gene of SPINT2 is commonly silenced by promoter hypermethylation in human ESCC and SPINT2 hypermethylation is correlated with poor overall survival, implicating SPINT2 is an underlying prognostic marker for human ESCC. - Highlights: • We firstly found SPINT2 gene may be transcriptionally repressed by promoter hypermethylation in ESCC cells. • SPINT2 overexpressing cells induced proliferation inhibition through promoting apoptosis. • mRNA expression of SPINT2 was significantly higher in ESCC tissues than in neighboring non-cancerous tissues. • Promoter hypermethylation of SPINT2 is significantly linked to TNM stage and poor overall survival.
Tsuzuku, T; Kaga, K
The relation between the results of vestibular function tests and gross motor development was examined in 4 children with inner ear anomalies. CT scans demonstrated the absence of lateral semicircular canals in both ears in all 4 cases. None responded to caloric stimulation using 40 ml of icewater. In contrast, the damped rotation test elicited per-rotatory nystagmus in all cases. Per-rotatory nystagmus was provoked in only two cases by the Bárány rotation test. Development of gross motor function, especially independent walking, was more delayed in the two children in whom the Bárány rotation test failed to elicit per-rotatory nystagmus.
Guillet, J.; Wynchank, S.; Basse-Cathalinat, B.; Christophe, E.; Ducassou, D.; Blanquet, P.
Esophageal transit of a small volume of watery liquid has been observed scintigraphically in 200 studies performed on patients aged between 6 days and 16 years. Qualitative information concerning esophageal morphology and function in the various phases of deglutition, and scintigraphic features of achalasia, stenosis, and other pathologies are described. Measured esophageal transit time and its normal variation, its relevance to the diagnosis of esophagitis, and the monitoring of treatment are discussed. This technique observing distinct deglutitions has proven a useful diagnostic tool. Its advantages and limitations are discussed in comparison with other methods.
Riehl, Megan E; Keefer, Laurie
Hypnotherapy is an evidence based intervention for the treatment of functional bowel disorders, particularly irritable bowel syndrome. While similar in pathophysiology, less is known about the utility of hypnotherapy in the upper gastrointestinal tract. Esophageal disorders, most of which are functional in nature, cause painful and uncomfortable symptoms that impact patient quality of life and are difficult to treat from a medical perspective. After a thorough medical workup and a failed trial of proton pump inhibitor therapy, options for treatment are significantly limited. While the pathophysiology is likely multifactorial, two critical factors are believed to drive esophageal symptoms--visceral hypersensitivity and symptom hypervigilance. The goal of esophageal directed hypnotherapy is to promote a deep state of relaxation with focused attention allowing the patient to learn to modulate physiological sensations and symptoms that are not easily addressed with conventional medical intervention. Currently, the use of hypnosis is suitable for dysphagia, globus, functional chest pain/non-cardiac chest pain, dyspepsia, and functional heartburn. In this article the authors will provide a rationale for the use of hypnosis in these disorders, presenting the science whenever available, describing their approach with these patients, and sharing a case study representing a successful outcome.
Bonzano, Laura; Palmaro, Eleonora; Teodorescu, Roxana; Fleysher, Lazar; Inglese, Matilde; Bove, Marco
Neuroimaging studies support the involvement of the cerebello-cortical and striato-cortical motor loops in motor sequence learning. Here, we investigated whether the gain of motor sequence learning could depend on a-priori resting-state functional connectivity (rsFC) between motor areas and structures belonging to these circuits. Fourteen healthy subjects underwent a resting-state functional magnetic resonance imaging session. Afterward, they were asked to reproduce a verbally-learned sequence of finger opposition movements as fast and as accurately as possible. All subjects increased their movement rate with practice, by reducing the touch duration and/or intertapping interval. The rsFC analysis showed that, at rest, the left and right primary motor cortex (M1) and left and right supplementary motor area (SMA) were mainly connected with other motor areas. The covariate analysis taking into account the different kinematic parameters indicated that the subjects achieving greater movement rate increase were those showing stronger rsFC of the left M1 and SMA with the right lobule VIII of the cerebellum. Notably, the subjects with greater intertapping interval reduction showed stronger rsFC of the left M1 and SMA with the association nuclei of the thalamus. Conversely, the regression analysis with the right M1 and SMA seeds showed only a few significant clusters for the different covariates not located in the cerebellum and thalamus. No common clusters were found between the right M1 and SMA. All of these findings indicated important functional connections at rest of those neural circuits responsible for motor learning improvement, involving the motor areas related to the hemisphere directly controlling the finger movements, the thalamus and cerebellum.
Sanz Mengibar, Jose Manuel; Santonja-Medina, Fernando; Sanchez-de-Muniain, Paloma; Canteras-Jordana, Manuel
Gross Motor Function Classification System has discriminative purposes but does not assess short-term therapy goals. Locomotion Stages (LS) classify postural body functions and independent activity components. Assessing the relation between Gross Motor Function Classification System level and Locomotion Stages will make us understand if clinical assessment can explain and predict motor environmental performance in cerebral palsy. A total of 462 children were assessed with both scales. High reliability and strong negative correlation (-0.908) for Gross Motor Function Classification System and Locomotion Stages at any age was found. Sensitivity was 83%, and specificity and positive predictive value were 100% within the same age range. Regression analysis showed detailed probabilities for the realization of the Gross Motor Function Classification System depending on the Locomotion Stages and the age group. Postural body function measure with Locomotion Stages is reliable, sensitive, and specific for gross motor function and able to predict environmental performance.
Combs, Hannah L; Jones, Theresa A; Kozlowski, Dorothy A; Adkins, DeAnna L
Cortical reorganization subsequent to post-stroke motor rehabilitative training (RT) has been extensively examined in animal models and humans. However, similar studies focused on the effects of motor training after traumatic brain injury (TBI) are lacking. We previously reported that after a moderate/severe TBI in adult male rats, functional improvements in forelimb use were accomplished only with a combination of skilled forelimb reach training and aerobic exercise, with or without nonimpaired forelimb constraint. Thus, the current study was designed to examine the relationship between functional motor cortical map reorganization after experimental TBI and the behavioral improvements resulting from this combinatorial rehabilitative regime. Adult male rats were trained to proficiency on a skilled reaching task, received a unilateral controlled cortical impact (CCI) over the forelimb area of the caudal motor cortex (CMC). Three days post-CCI, animals began RT (n = 13) or no rehabilitative training (NoRT) control procedures (n = 13). The RT group participated in daily skilled reach training, voluntary aerobic exercise, and nonimpaired forelimb constraint. This RT regimen significantly improved impaired forelimb reaching success and normalized reaching strategies, consistent with previous findings. RT also enlarged the area of motor cortical wrist representation, derived by intracortical microstimulation, compared to NoRT. These findings indicate that sufficient RT can greatly improve motor function and improve the functional integrity of remaining motor cortex after a moderate/severe CCI. When compared with findings from stroke models, these findings also suggest that more intense RT may be needed to improve motor function and remodel the injured cortex after TBI.
Nogueira, Solange F.; Figueiredo, Elyonara M.; Gonçalves, Rejane V.; Mancini, Marisa C.
Background: In children, reaching emerges around four months of age, which is followed by rapid changes in hand function and concomitant changes in gross motor function, including the acquisition of independent sitting. Although there is a close functional relationship between these domains, to date they have been investigated separately. Objective: To investigate the longitudinal profile of changes and the relationship between the development of hand function (i.e. reaching for and manipulating an object) and gross motor function in 13 normally developing children born at term who were evaluated every 15 days from 4 to 8 months of age. Method: The number of reaches and the period (i.e. time) of manipulation to an object were extracted from video synchronized with the Qualisys(r) movement analysis system. Gross motor function was measured using the Alberta Infant Motor Scale. ANOVA for repeated measures was used to test the effect of age on the number of reaches, the time of manipulation and gross motor function. Hierarchical regression models were used to test the associations of reaching and manipulation with gross motor function. Results: Results revealed a significant increase in the number of reaches (p<0.001), the time of manipulation (p<0.001) and gross motor function (p<0.001) over time, as well as associations between reaching and gross motor function (R2=0.84; p<0.001) and manipulation and gross motor function (R2=0.13; p=0.02) from 4 to 6 months of age. Associations from 6 to 8 months of age were not significant. Conclusion: The relationship between hand function and gross motor function was not constant, and the age span from 4 to 6 months was a critical period of interdependency of hand function and gross motor function development. PMID:25714437
[Purpose] This study attempted to investigate the effect of physical therapy frequency based on neurodevelopmental therapy on gross motor function in children with cerebral palsy. [Subjects and Methods] The study sample included 161 children with cerebral palsy who attended a convalescent or rehabilitation center for disabled individuals or a special school for children with physical disabilities in South Korea. Gross Motor Function Measure data were collected according to physical therapy frequency based on neurodevelopmental therapy for a period of 1 year. [Results] The correlation between physical therapy frequency and Gross Motor Function Measure scores for crawling and kneeling, standing, walking, running and jumping, and rolling, and the Gross Motor Function Measure total score was significant. The differences in gross motor function according to physical therapy frequency were significant for crawling, kneeling, standing, and Gross Motor Function Measure total score. The differences in gross motor function according to frequency of physical therapy were significant for standing in Gross Motor Function Classification System Level V. [Conclusion] Intensive physical therapy was more effective for improving gross motor function in children with cerebral palsy. In particular, crawling and kneeling, and standing ability showed greater increases with intensive physical therapy. PMID:27390440
[Purpose] This study attempted to investigate the effect of physical therapy frequency based on neurodevelopmental therapy on gross motor function in children with cerebral palsy. [Subjects and Methods] The study sample included 161 children with cerebral palsy who attended a convalescent or rehabilitation center for disabled individuals or a special school for children with physical disabilities in South Korea. Gross Motor Function Measure data were collected according to physical therapy frequency based on neurodevelopmental therapy for a period of 1 year. [Results] The correlation between physical therapy frequency and Gross Motor Function Measure scores for crawling and kneeling, standing, walking, running and jumping, and rolling, and the Gross Motor Function Measure total score was significant. The differences in gross motor function according to physical therapy frequency were significant for crawling, kneeling, standing, and Gross Motor Function Measure total score. The differences in gross motor function according to frequency of physical therapy were significant for standing in Gross Motor Function Classification System Level V. [Conclusion] Intensive physical therapy was more effective for improving gross motor function in children with cerebral palsy. In particular, crawling and kneeling, and standing ability showed greater increases with intensive physical therapy.
Eosinophilic esophagitis (EoE) is a newly recognized disease and is an emerging entity throughout developing and developed countries, including the United States. Therefore, understanding the causes, natural history, diagnosis, and management is important for future therapeutic interventions. The pathogenesis of EoE is still not clear, but a growing body of evidence has established that this condition represents a T-cell-mediated immune response involving several proinflammatory mediators and chemoattractants known to regulate eosinophilic accumulation in the esophagus, such as IL-4, IL-5, IL-3 and eotaxin-1, -2, and -3. Determining the mechanism or mechanisms through which human esophageal-derived factors ultimately induce the functional abnormalities observed, and to which antigens patients who have EoE are sensitized that lead to the manifestation of symptoms, is of significant interest.
Park, Eun Sook; Rha, Dong-Wook; Shin, Jung Soon; Kim, Soohyeon
Purpose The purpose of our study was to investigate the effects of hippotherapy on gross motor function and functional performance in children with spastic cerebral palsy (CP). Materials and Methods We recruited 34 children (M:F=15:19, age: 3-12 years) with spastic CP who underwent hippotherapy for 45 minutes twice a week for 8 weeks. Twenty-one children with spastic CP were recruited for control group. The distribution of gross motor function classification system level and mean age were not significantly different between the two groups. Outcome measures, including the Gross Motor Function Measure (GMFM)-66, GMFM-88 and the Pediatric Evaluation of Disability Inventory: Functional Skills Scale (PEDI-FSS), were assessed before therapy and after the 8-weeks intervention as outcome measures. Results There were no significant differences between intervention and control groups in mean baseline total scores of GMFM-66, GMFM-88 or PEDI-FSS. After the 8-weeks intervention, mean GMFM-66 and GMFM-88 scores were significantly improved in both groups. However, the hippotherapy group had significantly greater improvement in dimension E and GMFM-66 total score than the control group. The total PEDI-FSS score and the sub-scores of its 3 domains were significantly improved in the hippotherapy group, but not in the control group. Conclusion The results of our study demonstrate the beneficial effects of hippotherapy on gross motor function and functional performance in children with CP compared to control group. The significant improvement in PEDI-FSS scores suggests that hippotherapy may be useful to maximize the functional performance of children with CP. PMID:25323914
Lai, Chih-Jou; Liu, Wen-Yu; Yang, Tsui-Fen; Chen, Chia-Ling; Wu, Ching-Yi; Chan, Rai-Chi
This study investigates the effects of pediatric aquatic therapy on motor function, enjoyment, activities of daily living, and health-related quality of life for children with spastic cerebral palsy of various motor severities. Children with spastic cerebral palsy were assigned to a pediatric aquatic therapy group (n = 11; mean age = 85.0 ± 33.1 months; male : female = 4 : 7) or a control group (n = 13; mean age = 87.6 ± 34.0 months; male : female = 9 : 4). The statistic results indicate that the pediatric aquatic therapy group had greater average 66-item Gross Motor Function Measure following intervention than the control group (η(2) = 0.308, P = .007), even for children with Gross Motor Function Classification System level IV (5.0 vs 1.3). The pediatric aquatic therapy group had higher Physical Activity Enjoyment Scale scores than the control group at post-treatment (P = .015). These findings demonstrate that pediatric aquatic therapy can be an effective and alternative therapy for children with cerebral palsy even with poor Gross Motor Function Classification System level.
Lang, Ivan M; Medda, Bidyut K; Shaker, Reza
We studied the digestive and respiratory tract motor responses in 10 chronically instrumented dogs during eructation activated after feeding. Muscles were recorded from the cervical area, thorax, and abdomen. The striated muscles were recorded using EMG and the smooth muscles using strain gauges. We found eructation in three distinct functional phases that were composed of different sets of motor responses: gas escape, barrier elimination, and gas transport. The gas escape phase, activated by gastric distension, consists of relaxation of the lower esophageal sphincter and diaphragmatic hiatus and contraction of the longitudinal muscle of the thoracic esophagus and rectus abdominis. All these motor events promote gas escape from the stomach. The barrier elimination phase, probably activated by rapid gas distension of the thoracic esophagus, consists of relaxation of the pharyngeal constrictors and excitation of dorsal and ventral upper esophageal sphincter distracting muscles, as well as rapid contraction of the diaphragmatic dome fibers. These motor events allow esophagopharyngeal air movement by promoting retrograde airflow and opening of the upper esophageal sphincter. The transport phase, possibly activated secondary to diaphragmatic contraction, consists of a retrograde contraction of the striated muscle esophagus that transports the air from the thoracic esophagus to the pharynx. We hypothesize that the esophageal reverse peristalsis is mediated by elementary reflexes, rather than a coordinated peristaltic response like secondary peristalsis. The phases of eructation can be activated independently of one another or in a different manner to participate in physiological events other than eructation that cause gastroesophageal or esophagogastric reflux.
DiBella, Linda M.; Gorbatyuk, Oksana; Sakato, Miho; Wakabayashi, Ken-ichi; Patel-King, Ramila S.; Pazour, Gregory J.; Witman, George B.; King, Stephen M.
Tctex1 and Tctex2 were originally described as potential distorters/sterility factors in the non-Mendelian transmission of t-haplotypes in mice. These proteins have since been identified as subunits of cytoplasmic and/or axonemal dyneins. Within the Chlamydomonas flagellum, Tctex1 is a subunit of inner arm I1. We have now identified a second Tctex1-related protein (here termed LC9) in Chlamydomonas. LC9 copurifies with outer arm dynein in sucrose density gradients and is missing only in those strains completely lacking this motor. Zero-length cross-linking of purified outer arm dynein indicates that LC9 interacts directly with both the IC1 and IC2 intermediate chains. Immunoblot analysis revealed that LC2, LC6, and LC9 are missing in an IC2 mutant strain (oda6-r88) that can assemble outer arms but exhibits significantly reduced flagellar beat frequency. This defect is unlikely to be due to lack of LC6, because an LC6 null mutant (oda13) exhibits only a minor swimming abnormality. Using an LC2 null mutant (oda12-1), we find that although some outer arm dynein components assemble in the absence of LC2, they are nonfunctional. In contrast, dyneins from oda6-r88, which also lack LC2, retain some activity. Furthermore, we observed a synthetic assembly defect in an oda6-r88 oda12-1 double mutant. These data suggest that LC2, LC6, and LC9 have different roles in outer arm assembly and are required for wild-type motor function in the Chlamydomonas flagellum. PMID:16195342
Saito, Nen; Kaneko, Kunihiko
Protein motors, such as kinesins and dyneins, bind to a microtubule and travel along it in a specific direction. Previously, it was thought that the directionality for a given motor was constant in the absence of an external force. However, the directionality of the kinesin-5 Cin8 was recently found to change as the number of motors that bind to the same microtubule is increased. Here, we introduce a simple mechanical model of a microtubule-sliding assay in which multiple motors interact with the filament. We show that, due to the collective phenomenon, the directionality of the motor changes (e.g., from minus- to plus- end directionality), depending on the number of motors. This is induced by a large diffusive component in the directional walk and by the subsequent frustrated motor configuration, in which multiple motors pull the filament in opposite directions, similar to a game of tug-of-war. A possible role of the dual-directional motors for the mitotic spindle formation is also discussed. Our framework provides a general mechanism to embed two conflicting tasks into a single molecular machine, which works context-dependently.
Saito, Nen; Kaneko, Kunihiko
Protein motors, such as kinesins and dyneins, bind to a microtubule and travel along it in a specific direction. Previously, it was thought that the directionality for a given motor was constant in the absence of an external force. However, the directionality of the kinesin-5 Cin8 was recently found to change as the number of motors that bind to the same microtubule is increased. Here, we introduce a simple mechanical model of a microtubule-sliding assay in which multiple motors interact with the filament. We show that, due to the collective phenomenon, the directionality of the motor changes (e.g., from minus- to plus- end directionality), depending on the number of motors. This is induced by a large diffusive component in the directional walk and by the subsequent frustrated motor configuration, in which multiple motors pull the filament in opposite directions, similar to a game of tug-of-war. A possible role of the dual-directional motors for the mitotic spindle formation is also discussed. Our framework provides a general mechanism to embed two conflicting tasks into a single molecular machine, which works context-dependently. PMID:28281683
Smith, Barbara K.; Renno, Markus S.; Green, Meghan M.; Sexton, Terry M.; Lawson, Lee Ann; Martin, Anatole D.; Corti, Manuela; Byrne, Barry J.
Introduction Individuals with X-linked myotubular myopathy (XLMTM) and other centronuclear myopathies (CNMs) frequently have profound respiratory insufficiency that requires support early in life. Still, few quantitative data exist to characterize respiratory motor function in CNM. Methods We evaluated the reliance upon mechanical ventilation (MV), ventilatory kinematics, unassisted tidal volumes, and maximal respiratory pressures in 14 individuals with CNMs, including 10 boys with XLMTM. Results Thirteen participants required full-time, invasive MV. Maximal inspiratory pressures were higher in subjects who breathed unsupported at least 1 hour per day than 24-hour MV users [33.7 (11.9–42.3) vs 8.4 (6.0–10.9) cm H2O, P<0.05]. Years of MV dependence significantly correlated with MEP (r=−0.715, P<0.01). Discussion Respiratory function in CNMs may be related to deconditioning from prolonged MV and/or differences in residual respiratory muscle strength. Results from this study may assist in evaluating severe respiratory insufficiency in neuromuscular clinical care and research. PMID:26351754
Narayana, Shalini; Laird, Angela R; Tandon, Nitin; Franklin, Crystal; Lancaster, Jack L; Fox, Peter T
Neuro-imaging methods for detecting functional and structural inter-regional connectivity are in a rapid phase of development. While reports of regional connectivity patterns based on individual methods are becoming common, studies comparing the results of two or more connectivity-mapping methods remain rare. In this study, we applied transcranial magnetic stimulation during PET imaging (TMS/PET), a stimulation-based method, and meta-analytic connectivity modeling (MACM), a task-based method to map the connectivity patterns of the supplementary motor area (SMA). Further, we drew upon the behavioral domain meta-data of the BrainMap® database to characterize the behavioral domain specificity of two maps. Both MACM and TMS/PET detected multi-synaptic connectivity patterns, with the MACM-detected connections being more extensive. Both MACM and TMS/PET detected connections belonging to multiple behavioral domains, including action, cognition and perception. Finally, we show that the two connectivity-mapping methods are complementary in that, the MACM informed on the functional nature of SMA connections, while TMS/PET identified brain areas electrophysiologically connected with the SMA. Thus, we demonstrate that integrating multimodal database and imaging techniques can derive comprehensive connectivity maps of brain areas.
Whinnery, Stacie B.; Whinnery, Keith W.; Eddins, Daisy
This article addresses the challenges educators face when attempting to find a balance between both functional and academic skill instruction for students with severe, multiple disabilities including motor impairments. The authors describe a strategy that employs embedded instruction of early numeracy and functional motor skills during physical…
Nicotinic acetylcholine receptors (nAChR) are ligand-gated cation channels found throughout the body, and serve to mediate diverse physiological functions. Muscle-type nAChR located in the motor endplate region of muscle fibers play an integral role in muscle contraction and thus motor function. The...
London, Gábor; Chen, Kuang-Yen; Carroll, Gregory T; Feringa, Ben L
We report the synthesis of altitudinal molecular motors that contain functional groups in their rotor part. In an approach to achieve dynamic control over the properties of solid surfaces, a hydrophobic perfluorobutyl chain and a relatively hydrophilic cyano group were introduced to the rotor part of the motors. Molecular motors were attached to quartz surfaces by using interfacial 1,3-dipolar cycloadditions. To test the effect of the functional groups on the rotary motion, photochemical and thermal isomerization studies of the motors were performed both in solution and when attached to the surface. We found that the substituents have no significant effect on the thermal and photochemical processes, and the functionalized motors preserved their rotary function both in solution and on a quartz surface. Preliminary results on the influence of the functional groups on surface wettability are also described.
Sosnoff, Jacob J; Broglio, Steven P; Ferrara, Michael S
Mild traumatic brain injury (mTBI) causes deficits in motor and cognitive function. There is a dearth of research examining the association between these deficits. The purpose of this investigation was to examine the effect of mTBI on the association between cognitive and motor function. Thirty-six individuals completed a neurocognitive test battery and postural control assessment at baseline and were retested 24-h post mTBI. Reaction time and accuracy to various cognitive tasks was assessed. Postural control was indexed with the somatosenory organization test. This test allows for the decomposition of postural control resulting from the integration of visual, somatosensory and vestibular information. The association between cognitive and motor function was assessed with correlational analyses. Overall, it was found that mTBI resulted in increased simple and choice reaction time as well as deficits in verbal and visual memory. mTBI was also found to reduce overall postural control, especially when visual information was utilized. Prior to injury there was no association between cognitive and motor function-indicating minimal association between cognitive and motor function. After injury there were significant positive correlations between cognitive and motor function. The findings suggest that transient neural insults resulting from mTBI lead to increased cognitive-motor association. It is speculated that a shared neural process, such as visuospatial attention is damaged resulting in similar deficits in cognitive and motor function.
Nielsen, Glenn; Stone, Jon; Matthews, Audrey; Brown, Melanie; Sparkes, Chris; Farmer, Ross; Masterton, Lindsay; Duncan, Linsey; Winters, Alisa; Daniell, Laura; Lumsden, Carrie; Carson, Alan; David, Anthony S; Edwards, Mark
Background Patients with functional motor disorder (FMD) including weakness and paralysis are commonly referred to physiotherapists. There is growing evidence that physiotherapy is an effective treatment, but the existing literature has limited explanations of what physiotherapy should consist of and there are insufficient data to produce evidence-based guidelines. We aim to address this issue by presenting recommendations for physiotherapy treatment. Methods A meeting was held between physiotherapists, neurologists and neuropsychiatrists, all with extensive experience in treating FMD. A set of consensus recommendations were produced based on existing evidence and experience. Results We recommend that physiotherapy treatment is based on a biopsychosocial aetiological framework. Treatment should address illness beliefs, self-directed attention and abnormal habitual movement patterns through a process of education, movement retraining and self-management strategies within a positive and non-judgemental context. We provide specific examples of these strategies for different symptoms. Conclusions Physiotherapy has a key role in the multidisciplinary management of patients with FMD. There appear to be specific physiotherapy techniques which are useful in FMD and which are amenable to and require prospective evaluation. The processes involved in referral, treatment and discharge from physiotherapy should be considered carefully as a part of a treatment package. PMID:25433033
Wu, Pae C.; Knaack, Gretchen; Weber, Douglas J.
The rapid and exponential advances in micro- and nanotechnologies over the last decade have enabled devices that communicate directly with the nervous system to measure and influence neural activity. Many of the earliest implementations focused on restoration of sensory and motor function, but as knowledge of physiology advances and technology continues to improve in accuracy, precision, and safety, new modes of engaging with the autonomic system herald an era of health restoration that may augment or replace many conventional pharmacotherapies. DARPA's Biological Technologies Office is continuing to advance neurotechnology by investing in neural interface technologies that are effective, reliable, and safe for long-term use in humans. DARPA's Hand Proprioception and Touch Interfaces (HAPTIX) program is creating a fully implantable system that interfaces with peripheral nerves in amputees to enable natural control and sensation for prosthetic limbs. Beyond standard electrode implementations, the Electrical Prescriptions (ElectRx) program is investing in innovative approaches to minimally or non-invasively interface with the peripheral nervous system using novel magnetic, optogenetic, and ultrasound-based technologies. These new mechanisms of interrogating and stimulating the peripheral nervous system are driving towards unparalleled spatiotemporal resolution, specificity and targeting, and noninvasiveness to enable chronic, human-use applications in closed-loop neuromodulation for the treatment of disease.
Richter, Joel E
Tissue remodeling with scaring is common in adult EoE patients with long standing disease. This is the major factor contributing to their complaints of solid food dysphagia and recurrent food impactions. The best tests to define the degree of remodeling are barium esophagram, high resolution manometry and endoscopy. Many physicians are fearful to dilate EoE patients because of concerns about mucosal tears and perforations. However, multiple recent case series attest to the safety of esophageal dilation and its efficacy with many patients having symptom relief for an average of two years. This chapter will review the sordid history of esophageal dilation in EoE patients and outline how to perform this procedure safely. The key is graduated dilation over one to several sessions to a diameter of 15-18 mm. Postprocedural pain is to be expected and mucosal tears are a sign of successful dilation, not complications. In some healthy adults, occasional dilation may be preferred to regular use of medications or restricted diets. This approach is now supported by recent EoE consensus statements and societal guidelines.
Draper, Catherine E.; Achmat, Masturah; Forbes, Jared; Lambert, Estelle V.
The aims of the studies were to assess the impact of the Little Champs programme for motor development on (1) the gross motor skills, and (2) cognitive function of children in the programme. In study 1, 118 children from one Early Childhood Development Centre (ECDC) were tested using the Test of Gross Motor Development-2, and in study 2, 83…
Jensson, David; Weninger, Wolfgang J.; Schmid, Melanie; Meng, Stefan; Tzou, Chieh-Han John
Background: Injuries of the marginal mandibular nerve (MMN) of the facial nerve result in paralysis of the lower lip muscle depressors and an asymmetrical smile. Nerve reconstruction, when possible, is the method of choice; however, in cases of long nerve gaps or delayed nerve reconstruction, conventional nerve repairs may be difficult to perform or may provide suboptimal outcomes. Herein, we investigate the anatomical technical feasibility of transfer of the platysma motor nerve (PMN) to the MMN for restoration of lower lip function, and we present a clinical case where this nerve transfer was successfully performed. Methods: Ten adult fresh cadavers were dissected. Measurements included the number of MMN and PMN branches, the maximal length of dissection of the PMN from the parotid, and the distance from the anterior border of the parotid to the facial artery. The PMN reach for direct coaptation to the MMN at the level of the crossing with the facial artery was assessed. We performed histomorphometric analysis of the MMN and PMN branches. Results: The anatomy of the MMN and PMN was consistent in all dissections, with an average number of subbranches of 1.5 for the MMN and 1.2 for the PMN. The average maximal length of dissection of the PMN was 46.5 mm, and in every case, tension-free coaptation with the MMN was possible. Histomorphometric analysis demonstrated that the MMN contained an average of 3,866 myelinated fiber counts per millimeter, and the PMN contained 5,025. After a 3-year follow-up of the clinical case, complete recovery of MMN function was observed, without the need of central relearning and without functional or aesthetic impairment resulting from denervation of the platysma muscle. Conclusions: PMN to MMN transfer is an anatomically feasible procedure for reconstruction of isolated MMN injuries. In our patient, by direct nerve coaptation, a faster and full recovery of lower lip muscle depressors was achieved without the need of central
Ramírez Degollado, J; Martínez Aguilar, A; Peniche Bojórquez, J
Esophageal moniliasis is found rarely. It has been described mainly in chronically ill patients, who receive antibiotics and corticoesteroids. Early diagnosis and treatment betters their prognosis. Nine patients, 5 males and 4 females were studies in Hospital General del Centro Medico Nacional in Mexico City. Their agesranged from 26 to 77 years, with a mean of 49 years. All patients were chronically ill and 7 of them were treated in the intensive care unit. Three had disphagia, 3 retrosternal pain, and 2 gastrointestinal hemorrhage. Eight patients had high W.B.C., 3 irregular filling defects on X ray studies, and on endoscopy, all showed a pseudomembranous white yellowish exudate, underneath it the mucosa was inflamed, irregular and bled scantily. In 5 out of 9 patients biopsy and a smear confirmed the diagnosis. Eight patients treated with nystatin were cured. This disorder must be suspected in patients with disphagia and retrosternal pain; esophagoscopy is the prefered procedure to establish this diagnosis.
McGregor, Heather R.
Motor learning occurs not only through direct first-hand experience but also through observation (Mattar AA, Gribble PL. Neuron 46: 153–160, 2005). When observing the actions of others, we activate many of the same brain regions involved in performing those actions ourselves (Malfait N, Valyear KF, Culham JC, Anton JL, Brown LE, Gribble PL. J Cogn Neurosci 22: 1493–1503, 2010). Links between neural systems for vision and action have been reported in neurophysiological (Strafella AP, Paus T. Neuroreport 11: 2289–2292, 2000; Watkins KE, Strafella AP, Paus T. Neuropsychologia 41: 989–994, 2003), brain imaging (Buccino G, Binkofski F, Fink GR, Fadiga L, Fogassi L, Gallese V, Seitz RJ, Zilles K, Rizzolatti G, Freund HJ. Eur J Neurosci 13: 400–404, 2001; Iacoboni M, Woods RP, Brass M, Bekkering H, Mazziotta JC, Rizzolatti G. Science 286: 2526–2528, 1999), and eye tracking (Flanagan JR, Johansson RS. Nature 424: 769–771, 2003) studies. Here we used a force field learning paradigm coupled with resting-state fMRI to investigate the brain areas involved in motor learning by observing. We examined changes in resting-state functional connectivity (FC) after an observational learning task and found a network consisting of V5/MT, cerebellum, and primary motor and somatosensory cortices in which changes in FC were correlated with the amount of motor learning achieved through observation, as assessed behaviorally after resting-state fMRI scans. The observed FC changes in this network are not due to visual attention to motion or observation of movement errors but rather are specifically linked to motor learning. These results support the idea that brain networks linking action observation and motor control also facilitate motor learning. PMID:25995349
Memisevic, Haris; Sinanovic, Osman
The goal of this study was to assess the relationship between visual-motor integration and executive functions, and in particular, the extent to which executive functions can predict visual-motor integration skills in children with intellectual disability. The sample consisted of 90 children (54 boys, 36 girls; M age = 11.3 yr., SD = 2.7, range 7-15) with intellectual disabilities of various etiologies. The measure of executive functions were 8 subscales of the Behavioral Rating Inventory of Executive Function (BRIEF) consisting of Inhibition, Shifting, Emotional Control, Initiating, Working memory, Planning, Organization of material, and Monitoring. Visual-motor integration was measured with the Acadia test of visual-motor integration (VMI). Regression analysis revealed that BRIEF subscales explained 38% of the variance in VMI scores. Of all the BRIEF subscales, only two were statistically significant predictors of visual-motor integration: Working memory and Monitoring. Possible implications of this finding are further elaborated.
Bernardo, Janine; Friedman, Harriet; Minich, Nori; Taylor, H Gerry; Wilson-Costello, Deanne; Hack, Maureen
BACKGROUND: Rates of neurological impairment among extremely low birth weight children (ELBW [<1 kg]) have decreased since 2000; however, their functioning is unexamined. OBJECTIVE: To compare motor and cognitive functioning of ELBW children with neurological impairment, including cerebral palsy and severe hypotonia/hypertonia, between two periods: 1990 to 1999 (n=83) and 2000 to 2005 (n=34). METHODS: Measures of function at 20 months corrected age included the Mental and Psychomotor Developmental Indexes of the Bayley Scales of Infant Development and the Gross Motor Functional Classification System as primary outcomes and individual motor function items as secondary outcomes. RESULTS: Analysis failed to reveal significant differences for the primary outcomes, although during 2000 to 2005, sitting significantly improved in children with neurological impairment (P=0.003). CONCLUSION: Decreases in rates of neurological impairment among ELBW children have been accompanied by a suggestion of improved motor function, although cognitive function has not changed. PMID:26435676
Stavropoulos, Stavros N; Friedel, David; Modayil, Rani; Parkman, Henry P
Achalasia is a rare esophageal motility disorder that is usually idiopathic in origin. It is characterized by dysphagia, and patients often have chest pain, regurgitation, weight loss, and an abnormal barium radiograph showing esophageal dilation with narrowing at the gastroesophageal junction. Abnormal or absent esophageal peristalsis and impaired relaxation of the lower esophageal sphincter (LES) are typically seen on esophageal manometry. The advent of high resolution manometry (HRM) has allowed more precise diagnosis of achalasia, subtype designation, and differentiation from other esophageal motor disorders with an initial seminal publication in 2008 followed by further refinements of what has been termed the Chicago classification. Potential treatments include drugs, endoscopic botulinum toxin injection, balloon dilation, traditional surgery (usually laparoscopic Heller myotomy; LHM), and a novel, less invasive, natural orifice transluminal endoscopic surgery (NOTES) approach to Heller myotomy termed peroral endoscopic myotomy (POEM). The first human POEM was performed in 2008, with the first publication appearing in 2010 and evidence now rapidly accumulating showing POEM to be comparable to traditional surgery in terms of clinical success and radiologic and manometric post-therapy outcomes. This review discusses the diagnosis and management of achalasia with particular emphasis on the recent developments of HRM and POEM, which arguably represent the most important advances in the field since the advent of laparoscopic Heller myotomy in the 1990s.
Allievi, Alessandro G; Arichi, Tomoki; Tusor, Nora; Kimpton, Jessica; Arulkumaran, Sophie; Counsell, Serena J; Edwards, A David; Burdet, Etienne
Preterm birth engenders an increased risk of conditions like cerebral palsy and therefore this time may be crucial for the brain's developing sensori-motor system. However, little is known about how cortical sensori-motor function matures at this time, whether development is influenced by experience, and about its role in spontaneous motor behavior. We aimed to systematically characterize spatial and temporal maturation of sensori-motor functional brain activity across this period using functional MRI and a custom-made robotic stimulation device. We studied 57 infants aged from 30 + 2 to 43 + 2 weeks postmenstrual age. Following both induced and spontaneous right wrist movements, we saw consistent positive blood oxygen level-dependent functional responses in the contralateral (left) primary somatosensory and motor cortices. In addition, we saw a maturational trend toward faster, higher amplitude, and more spatially dispersed functional responses; and increasing integration of the ipsilateral hemisphere and sensori-motor associative areas. We also found that interhemispheric functional connectivity was significantly related to ex-utero exposure, suggesting the influence of experience-dependent mechanisms. At term equivalent age, we saw a decrease in both response amplitude and interhemispheric functional connectivity, and an increase in spatial specificity, culminating in the establishment of a sensori-motor functional response similar to that seen in adults.
Allievi, Alessandro G.; Arichi, Tomoki; Tusor, Nora; Kimpton, Jessica; Arulkumaran, Sophie; Counsell, Serena J.; Edwards, A. David; Burdet, Etienne
Preterm birth engenders an increased risk of conditions like cerebral palsy and therefore this time may be crucial for the brain's developing sensori-motor system. However, little is known about how cortical sensori-motor function matures at this time, whether development is influenced by experience, and about its role in spontaneous motor behavior. We aimed to systematically characterize spatial and temporal maturation of sensori-motor functional brain activity across this period using functional MRI and a custom-made robotic stimulation device. We studied 57 infants aged from 30 + 2 to 43 + 2 weeks postmenstrual age. Following both induced and spontaneous right wrist movements, we saw consistent positive blood oxygen level–dependent functional responses in the contralateral (left) primary somatosensory and motor cortices. In addition, we saw a maturational trend toward faster, higher amplitude, and more spatially dispersed functional responses; and increasing integration of the ipsilateral hemisphere and sensori-motor associative areas. We also found that interhemispheric functional connectivity was significantly related to ex-utero exposure, suggesting the influence of experience-dependent mechanisms. At term equivalent age, we saw a decrease in both response amplitude and interhemispheric functional connectivity, and an increase in spatial specificity, culminating in the establishment of a sensori-motor functional response similar to that seen in adults. PMID:26491066
Wei, Ran; Dong, Wei; Shen, Hongchang; Ni, Yang; Zhang, Tiehong; Wang, Yibing; Du, Jiajun
Pulmonary function tests had prospective implications for postoperative pneumonia, which occurred frequently after esophagectomy. Understanding factors that were associated with pulmonary infection may help in patient selection and postoperative management. We performed a retrospective review of 2 independent cohorts including 216 patients who underwent esophagectomy between November 2011 and May 2014, aiming at identifying predictors of primary pneumonia. Univariate analysis was used to identify potential covariates for the development of primary pneumonia. Adjustments for multiple comparisons were made using False Discovery Rate (FDR) (Holm-Bonferroni method). Multivariable logistic regression analysis was used to identify independent predictors and construct a regression model based on a training cohort (n = 166) and then the regression model was validated using an independent cohort (n = 50). It showed that low PEF (hazard ratio 0.97, P = 0.009) was independent risk factors for the development of primary pneumonia in multivariate analyses and had a predictive effect for primary pneumonia (AUC = 0.691 and 0.851 for training and validation data set, respectively). Therefore, PEF has clinical value in predicting postoperative pneumonia after esophagectomy and it may serve as an indicator of preoperative lung function training.
Vitenzon, A S; Mironov, E M; Petrushanskaya, K A
The main functions of a method of functional electrical stimulation of muscles (FES) are described: diagnostic, prognostic, and therapeutic. The main indication for using the FES method is a deficiency of muscle function, which may be organic (due to lesions to neuromuscular structures) or functional (associated with relaxation of the muscular apparatus). The five most significant functions of the FES method were established: 1) identification of correctable movements and stimulable muscles; 2) identification of the amplitude and time program for stimulation; 3) stimulation regimes for pathological gaits; 4) stimulation parameters; 5) positioning of skin electrodes on the human body. Using the example of two severe central nervous system pathologies (spinal cord lesions in the lumbosacral area and hemiparesis of cerebral origin), the positive effects of FES on the process of motor rehabilitation of this category of patients were demonstrated.
Ramanathan, Dhakshin; Conner, James M.; H. Tuszynski, Mark
To investigate functional mechanisms underlying cortical motor plasticity in the intact and injured brain, we used “behaviorally relevant,” long-duration intracortical microstimulation. We now report the existence of complex, multijoint movements revealed with a 500-msec duration intracortical stimulation in rat motor cortex. A consistent topographic distribution of these complex motor patterns is present across the motor cortex in naïve rats. We further document the plasticity of these complex movement patterns after focal cortical injury, with a significant expansion of specific complex movement representations in response to rehabilitative training after injury. Notably, the degree of functional recovery attained after cortical injury and rehabilitation correlates significantly with a specific feature of map reorganization, the ability to reexpress movement patterns disrupted by the initial injury. This evidence suggests the existence of complex movement representations in the rat motor cortex that exhibit plasticity after injury and rehabilitation, serving as a relevant predictor of functional recovery. PMID:16837575
Son, Sung Wook; Kim, Seok-Hyung; Moon, Eun-Yi; Kim, Dong-Hoon; Pyo, Suhkneung; Um, Sung Hee
Vacuolar H+-ATPase (V-ATPase), a hetero-multimeric ATP-driven proton pump has recently emerged as a critical regulator of mTOR-induced amino acid sensing for cell growth. Although dysregulated activity of cell growth regulators is often associated with cancer, the prognostic significance and metabolic roles of V-ATPase in esophageal cancer progression remain unclear. Here, we show that high levels of V-ATPase subunit V1E1 (V-ATPase V1E1) were significantly associated with shortened disease-free survival in patients with esophageal squamous cell carcinoma (ESCC). Multivariate analysis identified the V-ATPase V1E1 as an independent adverse prognostic factor (hazard ratio;1.748, P = 0.018). In addition, depletion of V-ATPase V1E1 resulted in reduced cell motility, decreased glucose uptake, diminished levels of lactate, and decreased ATP production, as well as inhibition of glycolytic enzyme expression in TE8 esophageal cancer cells. Consistent with these results, the Cancer Genome Atlas (TCGA) data and Gene Set Enrichment Analysis (GSEA) showed a high frequency of copy number alterations of the V-ATPase V1E1 gene, and identified a correlation between levels of V-ATPase V1E1 mRNA and Pyruvate Kinase M2 (PKM2) in ESCC. High expression levels of both V-ATPase V1E1 and phosphorylated PKM2 (p-PKM2), a key player in cancer metabolism, were associated with poorer prognosis in ESCC. Collectively, our findings suggest that expression of the V-ATPase V1E1 has prognostic significance in ESCC, and is closely linked to migration, invasion, and aerobic glycolysis in esophageal cancer cells.
Kim, Dong-Hoon; Pyo, Suhkneung; Um, Sung Hee
Vacuolar H+-ATPase (V-ATPase), a hetero-multimeric ATP-driven proton pump has recently emerged as a critical regulator of mTOR-induced amino acid sensing for cell growth. Although dysregulated activity of cell growth regulators is often associated with cancer, the prognostic significance and metabolic roles of V-ATPase in esophageal cancer progression remain unclear. Here, we show that high levels of V-ATPase subunit V1E1 (V-ATPase V1E1) were significantly associated with shortened disease-free survival in patients with esophageal squamous cell carcinoma (ESCC). Multivariate analysis identified the V-ATPase V1E1 as an independent adverse prognostic factor (hazard ratio;1.748, P = 0.018). In addition, depletion of V-ATPase V1E1 resulted in reduced cell motility, decreased glucose uptake, diminished levels of lactate, and decreased ATP production, as well as inhibition of glycolytic enzyme expression in TE8 esophageal cancer cells. Consistent with these results, the Cancer Genome Atlas (TCGA) data and Gene Set Enrichment Analysis (GSEA) showed a high frequency of copy number alterations of the V-ATPase V1E1 gene, and identified a correlation between levels of V-ATPase V1E1 mRNA and Pyruvate Kinase M2 (PKM2) in ESCC. High expression levels of both V-ATPase V1E1 and phosphorylated PKM2 (p-PKM2), a key player in cancer metabolism, were associated with poorer prognosis in ESCC. Collectively, our findings suggest that expression of the V-ATPase V1E1 has prognostic significance in ESCC, and is closely linked to migration, invasion, and aerobic glycolysis in esophageal cancer cells. PMID:27384996
Subramanian, Leena; Morris, Monica Busse; Brosnan, Meadhbh; Turner, Duncan L.; Morris, Huw R.; Linden, David E. J.
Objective: Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback (NF) uses feedback of the patient’s own brain activity to self-regulate brain networks which in turn could lead to a change in behavior and clinical symptoms. The objective was to determine the effect of NF and motor training (MOT) alone on motor and non-motor functions in Parkinson’s Disease (PD) in a 10-week small Phase I randomized controlled trial. Methods: Thirty patients with Parkinson’s disease (PD; Hoehn and Yahr I-III) and no significant comorbidity took part in the trial with random allocation to two groups. Group 1 (NF: 15 patients) received rt-fMRI-NF with MOT. Group 2 (MOT: 15 patients) received MOT alone. The primary outcome measure was the Movement Disorder Society—Unified PD Rating Scale-Motor scale (MDS-UPDRS-MS), administered pre- and post-intervention “off-medication”. The secondary outcome measures were the “on-medication” MDS-UPDRS, the PD Questionnaire-39, and quantitative motor assessments after 4 and 10 weeks. Results: Patients in the NF group were able to upregulate activity in the supplementary motor area (SMA) by using motor imagery. They improved by an average of 4.5 points on the MDS-UPDRS-MS in the “off-medication” state (95% confidence interval: −2.5 to −6.6), whereas the MOT group improved only by 1.9 points (95% confidence interval +3.2 to −6.8). The improvement in the intervention group meets the minimal clinically important difference which is also on par with other non-invasive therapies such as repetitive Transcranial Magnetic Stimulation (rTMS). However, the improvement did not differ significantly between the groups. No adverse events were reported in either group. Interpretation: This Phase I study suggests that NF combined with MOT is safe and improves motor symptoms immediately after treatment, but larger trials are needed to explore its superiority over active control conditions. PMID:27375451
De Bellis, Francesco; Ferrara, Antonia; Errico, Domenico; Panico, Francesco; Sagliano, Laura; Conson, Massimiliano; Trojano, Luigi
Recent evidence shows that activation of motor information can favor identification of related tools, thus suggesting a strict link between motor and conceptual knowledge in cognitive representation of tools. However, the involvement of motor information in further semantic processing has not been elucidated. In three experiments, we aimed to ascertain whether motor information provided by observation of actions could affect processing of conceptual knowledge about tools. In Experiment 1, healthy participants judged whether pairs of tools evoking different functional handgrips had the same function. In Experiment 2 participants judged whether tools were paired with appropriate recipients. Finally, in Experiment 3 we again required functional judgments as in Experiment 1, but also included in the set of stimuli pairs of objects having different function and similar functional handgrips. In all experiments, pictures displaying either functional grasping (aimed to use tools) or structural grasping (just aimed to move tools independently from their use) were presented before each stimulus pair. The results demonstrated that, in comparison with structural grasping, observing functional grasping facilitates judgments about tools' function when objects did not imply the same functional manipulation (Experiment 1), whereas worsened such judgments when objects shared functional grasp (Experiment 3). Instead, action observation did not affect judgments concerning tool-recipient associations (Experiment 2). Our findings support a task-dependent influence of motor information on high-order conceptual tasks and provide further insights into how motor and conceptual processing about tools can interact.
Kim, Myoung Sook; Huang, Yiping; Lee, Juna; Zhong, Xiaoli; Jiang, Wei-Wen; Ratovitski, Edward A; Sidransky, David
Cigarette-smoking increases the risk of developing various types of human cancers including esophageal cancers. To test the effects of chronic cigarette smoke exposure directly on esophageal epithelium, cellular resistance to mainstream extract (MSE), or sidestream smoke extract (SSE) was developed in chronically exposed nonmalignant Het-1A cells. Anchorage-independent growth, in vitro invasion capacity and proliferation of the resistant cells increased compared with the unexposed, sensitive cells. An epithelial marker E-cadherin was down-regulated and mesenchymal markers N-cadherin and vimentin were up-regulated in the resistant cells. Het-1A cells resistant to MSE or SSE consumed more glucose, and produced more lactate than the sensitive cells. The increased anchorage-independent cell growth of the resistant cells was suppressed by a glycolysis inhibitor, 2-deoxy-D-glucose, indicating that these cells are highly dependent on the glycolytic pathway for survival. Decreased mitochondrial membrane potential and ATP production in the resistant cells indicate the presence of mitochondrial dysfunction induced by chronic exposure of cigarette smoke extract. Increased expression of nuclear genes in the glycolytic pathway and decreased levels of mitochondrial genes in the resistant cells support the notion that cigarette smoking significantly contributes to the transformation of nonmalignant esophageal epithelial cells into a tumorigenic phenotype.
Li, Yaqing; Li, Xiaoran; Kan, Quancheng; Zhang, Mingzhi; Li, Xiaoli; Xu, Ruiping; Wang, Junsheng; Yu, Dandan; Goscinski, Mariusz Adam; Wen, Jian-Guo; Nesland, Jahn M.; Suo, Zhenhe
Aerobic glycolysis is one of the emerging hallmarks of cancer cells. In this study, we investigated the relationship between blocking mitochondrial pyruvate carrier (MPC) with MPC blocker UK5099 and the metabolic alteration as well as aggressive features of esophageal squamous carcinoma. It was found that blocking pyruvate transportation into mitochondria attenuated mitochondrial oxidative phosphorylation (OXPHOS) and triggered aerobic glycolysis, a feature of Warburg effect. In addition, the HIF-1α expression and ROS production were also activated upon UK5099 application. It was further revealed that the UK5099-treated cells became significantly more resistant to chemotherapy and radiotherapy, and the UK5099-treated tumor cells also exhibited stronger invasive capacity compared to the parental cells. In contrast to esophageal squamous epithelium cells, decreased MPC protein expression was observed in a series of 157 human squamous cell carcinomas, and low/negative MPC1 expression predicted an unfavorable clinical outcome. All these results together revealed the potential connection of altered MPC expression/activity with the Warburg metabolic reprogramming and tumor aggressiveness in cell lines and clinical samples. Collectively, our findings highlighted a therapeutic strategy targeting Warburg reprogramming of human esophageal squamous cell carcinomas. PMID:27911865
Rigoli, Daniela; Piek, Jan P.; Kane, Robert; Oosterlaan, Jaap
Aim: Research suggests important links between motor coordination and executive functions. The current study examined whether motor coordination predicts working memory, inhibition, and switching performance, extending previous research by accounting for attention-deficit-hyperactivity disorder (ADHD) symptomatology and other confounding factors,…
Vuijk, P. J.; Hartman, E.; Scherder, E.; Visscher, C.
Background: There is a relatively small body of research on the motor performance of children with mild intellectual disabilities (MID) and borderline intellectual functioning (BIF). Adequate levels of motor skills may contribute to lifelong enjoyment of physical activity, participation in sports and healthy lifestyles. The present study compares…
Cameron, Claire E.; Brock, Laura L.; Murrah, William M.; Bell, Lindsay H.; Worzalla, Samantha L.; Grissmer, David; Morrison, Frederick J.
This study examined the contribution of executive function (EF) and multiple aspects of fine motor skills to achievement on 6 standardized assessments in a sample of middle-socioeconomic status kindergarteners. Three- and 4-year-olds' (n = 213) fine and gross motor skills were assessed in a home visit before kindergarten, EF was measured at fall…
Johnson-Frey, Scott H.
A key factor influencing reorganization of function in damaged neural networks of the adult brain is stimulation. How to stimulate motor areas of patients with paralyses is a formidable challenge. One possibility is to use internal movement simulations, or motor imagery, as an alternative to conventional therapeutic interventions that require…
Hartman, E.; Houwen, S.; Scherder, E.; Visscher, C.
Background: It has been suggested that children with intellectual disabilities (ID) have motor problems and higher-order cognitive deficits. The aim of this study was to examine the motor skills and executive functions in school-age children with borderline and mild ID. The second aim was to investigate the relationship between the two performance…
Schott, N.; Holfelder, B.
Background: Previous studies suggest that children with Down's syndrome (DS), a genetically based neurodevelopmental disorder, demonstrate motor problems and cognitive deficits. The first aim of this study was to examine motor skills and executive functions (EFs) in school-age children with DS. The second aim was to investigate the relationship…
Caproni, Stefano; Muti, Marco; Principi, Massimo; Ottaviano, Pierfausto; Frondizi, Domenico; Capocchi, Giuseppe; Floridi, Piero; Rossi, Aroldo; Calabresi, Paolo; Tambasco, Nicola
Motor impairment is the most relevant clinical feature in Parkinson's disease (PD). Functional imaging studies on motor impairment in PD have revealed changes in the cortical motor circuits, with particular involvement of the fronto-striatal network. The aim of this study was to assess brain activations during the performance of three different motor exercises, characterized by progressive complexity, using a functional fMRI multiple block paradigm, in PD patients and matched control subjects. Unlike from single-task comparisons, multi-task comparisons between similar exercises allowed to analyse brain areas involved in motor complexity planning and execution. Our results showed that in the single-task comparisons the involvement of primary and secondary motor areas was observed, consistent with previous findings based on similar paradigms. Most notably, in the multi-task comparisons a greater activation of supplementary motor area and posterior parietal cortex in PD patients, compared with controls, was observed. Furthermore, PD patients, compared with controls, had a lower activation of the basal ganglia and limbic structures, presumably leading to the impairment in the higher levels of motor control, including complexity planning and execution. The findings suggest that in PD patients occur both compensatory mechanisms and loss of efficiency and provide further insight into the pathophysiological role of distinct cortical and subcortical areas in motor dysfunction. PMID:23825570
Caproni, Stefano; Muti, Marco; Principi, Massimo; Ottaviano, Pierfausto; Frondizi, Domenico; Capocchi, Giuseppe; Floridi, Piero; Rossi, Aroldo; Calabresi, Paolo; Tambasco, Nicola
Motor impairment is the most relevant clinical feature in Parkinson's disease (PD). Functional imaging studies on motor impairment in PD have revealed changes in the cortical motor circuits, with particular involvement of the fronto-striatal network. The aim of this study was to assess brain activations during the performance of three different motor exercises, characterized by progressive complexity, using a functional fMRI multiple block paradigm, in PD patients and matched control subjects. Unlike from single-task comparisons, multi-task comparisons between similar exercises allowed to analyse brain areas involved in motor complexity planning and execution. Our results showed that in the single-task comparisons the involvement of primary and secondary motor areas was observed, consistent with previous findings based on similar paradigms. Most notably, in the multi-task comparisons a greater activation of supplementary motor area and posterior parietal cortex in PD patients, compared with controls, was observed. Furthermore, PD patients, compared with controls, had a lower activation of the basal ganglia and limbic structures, presumably leading to the impairment in the higher levels of motor control, including complexity planning and execution. The findings suggest that in PD patients occur both compensatory mechanisms and loss of efficiency and provide further insight into the pathophysiological role of distinct cortical and subcortical areas in motor dysfunction.
AWARD NUMBER: W81XWH-14-1-0189 TITLE: Muscle-Derived GDNF: A Gene Therapeutic Approach for Preserving Motor Neuron Function in ALS PRINCIPAL...NUMBER W81XWH-14-1-0189 Muscle-Derived GDNF: A Gene Therapeutic Approach for Preserving Motor Neuron Function in ALS 5b. GRANT NUMBER 5c. PROGRAM...production in muscles. Hypothesis: Intramuscular AAV5-GDNF injection will ameliorate motor neuron function in the SOD1G93A rat model of ALS. Objectives
Kobylecka, Małgorzata; Olesińska, Marzena
Systemic sclerosis is a rare connective tissue disease, distinctive features of which are fibrosis and microangiopathy. The esophagus is one of the most commonly involved internal organs. Most patients experience dysphagia, difficulties in swallowing and gastro-esophageal reflux. However, in up to one third of cases, the initial onset of esophageal disease may be clinically silent. There are several diagnostic modalities available for assessing both morphological and functional abnormalities of the esophagus. If structural abnormalities are suspected, endoscopy is the method of choice. Functional evaluation is best achieved with manometry. Both endoscopy and manometry are invasive techniques, with low patient acceptance. Barium-contrast study is well tolerated, but qualitative assessment of functional abnormalities is imprecise. Esophageal scintigraphy is an easy, non-invasive, sensitive and specific diagnostic modality. It can detect esophageal dysfunction even in asymptomatic patients. In patients already diagnosed with systemic sclerosis, scintigraphy is useful in evaluating severity and progression of the disease. PMID:27994270
Chojnowski, Marek; Kobylecka, Małgorzata; Olesińska, Marzena
Systemic sclerosis is a rare connective tissue disease, distinctive features of which are fibrosis and microangiopathy. The esophagus is one of the most commonly involved internal organs. Most patients experience dysphagia, difficulties in swallowing and gastro-esophageal reflux. However, in up to one third of cases, the initial onset of esophageal disease may be clinically silent. There are several diagnostic modalities available for assessing both morphological and functional abnormalities of the esophagus. If structural abnormalities are suspected, endoscopy is the method of choice. Functional evaluation is best achieved with manometry. Both endoscopy and manometry are invasive techniques, with low patient acceptance. Barium-contrast study is well tolerated, but qualitative assessment of functional abnormalities is imprecise. Esophageal scintigraphy is an easy, non-invasive, sensitive and specific diagnostic modality. It can detect esophageal dysfunction even in asymptomatic patients. In patients already diagnosed with systemic sclerosis, scintigraphy is useful in evaluating severity and progression of the disease.
Volz, L J; Rehme, A K; Michely, J; Nettekoven, C; Eickhoff, S B; Fink, G R; Grefkes, C
Neural plasticity is a major factor driving cortical reorganization after stroke. We here tested whether repetitively enhancing motor cortex plasticity by means of intermittent theta-burst stimulation (iTBS) prior to physiotherapy might promote recovery of function early after stroke. Functional magnetic resonance imaging (fMRI) was used to elucidate underlying neural mechanisms. Twenty-six hospitalized, first-ever stroke patients (time since stroke: 1-16 days) with hand motor deficits were enrolled in a sham-controlled design and pseudo-randomized into 2 groups. iTBS was administered prior to physiotherapy on 5 consecutive days either over ipsilesional primary motor cortex (M1-stimulation group) or parieto-occipital vertex (control-stimulation group). Hand motor function, cortical excitability, and resting-state fMRI were assessed 1 day prior to the first stimulation and 1 day after the last stimulation. Recovery of grip strength was significantly stronger in the M1-stimulation compared to the control-stimulation group. Higher levels of motor network connectivity were associated with better motor outcome. Consistently, control-stimulated patients featured a decrease in intra- and interhemispheric connectivity of the motor network, which was absent in the M1-stimulation group. Hence, adding iTBS to prime physiotherapy in recovering stroke patients seems to interfere with motor network degradation, possibly reflecting alleviation of post-stroke diaschisis.
Scholey, Jonathan M
Kinesin-2 was first purified as a heterotrimeric, anterograde, microtubule-based motor consisting of two distinct kinesin-related subunits and a novel associated protein (KAP) that is currently best known for its role in intraflagellar transport and ciliogenesis. Subsequent work, however, has revealed diversity in the oligomeric state of different kinesin-2 motors owing to the combinatorial heterodimerization of its subunits and the coexistence of both heterotrimeric and homodimeric kinesin-2 motors in some cells. Although the functional significance of the homo- versus heteromeric organization of kinesin-2 motor subunits and the role of KAP remain uncertain, functional studies suggest that cooperation between different types of kinesin-2 motors or between kinesin-2 and a member of a different motor family can generate diverse patterns of anterograde intracellular transport. Moreover, despite being restricted to ciliated eukaryotes, kinesin-2 motors are now known to drive diverse transport events outside cilia. Here, I review the organization, assembly, phylogeny, biological functions, and motility mechanism of this diverse family of intracellular transport motors.
Curado, Marco; Fritsch, Brita; Reis, Janine
Non-invasive electrical brain stimulation (NEBS) is used to modulate brain function and behavior, both for research and clinical purposes. In particular, NEBS can be applied transcranially either as direct current stimulation (tDCS) or alternating current stimulation (tACS). These stimulation types exert time-, dose- and in the case of tDCS polarity-specific effects on motor function and skill learning in healthy subjects. Lately, tDCS has been used to augment the therapy of motor disabilities in patients with stroke or movement disorders. This article provides a step-by-step protocol for targeting the primary motor cortex with tDCS and transcranial random noise stimulation (tRNS), a specific form of tACS using an electrical current applied randomly within a pre-defined frequency range. The setup of two different stimulation montages is explained. In both montages the emitting electrode (the anode for tDCS) is placed on the primary motor cortex of interest. For unilateral motor cortex stimulation the receiving electrode is placed on the contralateral forehead while for bilateral motor cortex stimulation the receiving electrode is placed on the opposite primary motor cortex. The advantages and disadvantages of each montage for the modulation of cortical excitability and motor function including learning are discussed, as well as safety, tolerability and blinding aspects.
Woolley, Daniel G.
Cross-education (CE) is the process whereby training with one limb leads to subsequent improvement in performance by the opposite untrained limb. We used multimodal neuroimaging in humans to investigate the mediating neural mechanisms by relating quantitative estimates of functional and structural cortical connectivity to individual levels of interlimb transfer. Resting-state (rs)-fMRI and diffusion weighted imaging (DWI) scans were undertaken before unilateral ballistic wrist flexion training. The rs-fMRI sequence was repeated immediately afterward. The increase in performance of the untrained limb was 83.6% of that observed for the trained limb and significantly greater than that of a control group who undertook no training. Functional connectivity in the resting motor network between right and left supplementary motor areas (SMA) was elevated after training. These changes were not, however, correlated with individual levels of transfer. Analysis of the DWI data using constrained spherical deconvolution-based tractography indicated that fractional anisotropy and apparent fiber density in tracts connecting bilateral SMA were negatively correlated with and predictive of transfer. The findings suggest that interhemispheric interactions between bilateral SMA play an instrumental role in CE and that the structural integrity of the connecting white matter pathways influences the level of transfer. SIGNIFICANCE STATEMENT Strength or skill training with one limb also brings about improvements in the performance of the opposite, untrained limb. This phenomenon, termed cross-education (CE), has obvious potential for the rehabilitation of functional capacity that has been lost through brain insult or musculoskeletal injury. The neural mechanisms that give rise to CE are, however, poorly understood. We used a combination of neuroimaging methods to investigate the pathways in the human brain that mediate CE. We determined that the supplementary motor area (SMA) plays an
Krammer, Matthias Johannes; Wolf, Stefan; Schul, David Baruch; Gerstner, Werner; Lumenta, Christianto Bernardo
Intraoperative motor evoked potential (MEP) monitoring in patients with spinal and cranial lesions is thought to be a valuable tool for prevention of postoperative motor deficits. Aim of this study was to investigate its diagnostic value in a spinal and a cranial patient group. Ninety-six patients, 31 with spinal and 65 with intracranial lesions, were studied. Transcranial stimulation was performed with a high-frequency electrical train stimulation using two subdermal needle electrodes. MEPs were recorded from the pathology-related muscles. Decreasing amplitudes of 50% or more, increasing stimulus intensities of 20% or more or increased latencies were taken as warning criteria. MEP recording was possible in 90% of the spinal and 98% of the cranial group. With two further exclusions, 28 patients of the spinal and 62 of the cranial group were analyzed. We saw a temporary maximum amplitude reduction of 50% or more and an increase in stimulation intensity of 20% or more in 8 spinal and 29 cranial patients. Five of the spinal and nine of the cranial patients deteriorated in motor function postoperatively. One patient with normal MEP monitoring showed a temporary motor weakness postoperatively. Latencies were normal in all patients. Given both warning criteria, intraoperative MEP changes had a sensitivity of 83%/ 100% and a specificity of 86%/ 62% (spinal/ cranial group). The positive predictive value of MEP changes for postoperative motor function deterioration was 63%/ 31%, and the negative predictive value was 95%/ 100%. Transcranial electrical monitoring of MEP is a practicable and safe method. However, there are many events, which can cause amplitude changes of MEP independent from surgical manipulations. Although sensitivity is high for both groups, this results in a moderate specificity for the cranial group and a low positive predictive value for both groups.
Aged rats show impaired performance on motor and cognitive tasks that require the use of spatial learning and memory. In previous studies, we have shown the beneficial effects of various berry fruits (blueberries, strawberries, and blackberries) in reversing age-related deficits in behavioral and ne...
Böhm, Birgitta; Lundequist, Aiko; Smedler, Ann-Charlotte
Visual-motor development and executive functions were investigated with the Bender Test at age 5½ years in 175 children born preterm and 125 full-term controls, within the longitudinal Stockholm Neonatal Project. Assessment also included WPPSI-R and NEPSY neuropsychological battery for ages 4-7 (Korkman, 1990). Bender protocols were scored according to Brannigan & Decker (2003), Koppitz (1963) and a complementary neuropsychological scoring system (ABC), aimed at executive functions and developed for this study. Bender results by all three scoring systems were strongly related to overall cognitive level (Performance IQ), in both groups. The preterm group displayed inferior visual-motor skills compared to controls also when controlling for IQ. The largest group differences were found on the ABC scoring, which shared unique variance with NEPSY tests of executive function. Multiple regression analyses showed that hyperactive behavior and inattention increased the risk for visual-motor deficits in children born preterm, whereas no added risk was seen among hyperactive term children. Gender differences favoring girls were strongest within the preterm group, presumably reflecting the specific vulnerability of preterm boys. The results indicate that preterm children develop a different neurobehavioral organization from children born at term, and that the Bender test with a neuropsychological scoring is a useful tool in developmental screening around school start.
Hamada, Junichi; Shoda, Katsutoshi; Masuda, Kiyoshi; Fujita, Yuji; Naruto, Takuya; Kohmoto, Tomohiro; Miyakami, Yuko; Watanabe, Miki; Kudo, Yasusei; Fujiwara, Hitoshi; Ichikawa, Daisuke; Otsuji, Eigo; Imoto, Issei
T-cell intracellular antigen-1 (TIA1) is an RNA-binding protein involved in many regulatory aspects of mRNA metabolism. Here, we report previously unknown tumor-promoting activity of TIA1, which seems to be associated with its isoform-specific molecular distribution and regulation of a set of cancer-related transcripts, in esophageal squamous cell carcinoma (ESCC). Immunohistochemical overexpression of TIA1 ectopically localized in the cytoplasm of tumor cells was an independent prognosticator for worse overall survival in a cohort of 143 ESCC patients. Knockdown of TIA1 inhibited proliferation of ESCC cells. By exogenously introducing each of two major isoforms, TIA1a and TIA1b, only TIA1a, which was localized to both the nucleus and cytoplasm, promoted anchorage-dependent and anchorage-independent ESCC cell proliferation. Ribonucleoprotein immunoprecipitation, followed by microarray analysis or massive-parallel sequencing, identified a set of TIA1-binding mRNAs, including SKP2 and CCNA2. TIA1 increased SKP2 and CCNA2 protein levels through the suppression of mRNA decay and translational induction, respectively. Our findings uncover a novel oncogenic function of TIA1 in esophageal tumorigenesis, and implicate its use as a marker for prognostic evaluation and as a therapeutic target in ESCC.
Kuppan, Purushothaman; Sethuraman, Swaminathan; Krishnan, Uma Maheswari
Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and PHBV-gelatin were electrospun to obtain defect-free nanofibers by optimizing various process and solution parameters. Tensile strength, Young's modulus, and wettability of PHBV-gelatin nanofibrous scaffold were determined and compared with PHBV nanofibrous scaffold. Our results demonstrate that PHBV-gelatin nanofibers exhibited higher tensile strength and Young's modulus than the PHBV nanofibers. Human esophageal epithelial cells (HEEpiC) were cultured on PHBV and PHBV-gelatin nanofiber showed better cell proliferation in PHBV nanofibrous scaffold than the PHBV-gelatin scaffold after 7 days of culture. HEEpiC cultured on PHBV and PHBV-gelatin nanofibrous scaffold exhibited characteristic epithelial cobblestone morphology after 3 days of culture. Further, the HEEpiC extracellular matrix (ECM) proteins (collagen type IV and laminin) and phenotypic marker proteins (cytokeratin-4 and 14) expressions were significantly higher in PHBV-gelatin nanofibrous scaffold than the PHBV nanofiber scaffold. However, the long-term stability and functional state of the cells on the PHBV scaffold give it an edge over the blend scaffolds. Thus, PHBV-based nanofibrous scaffolds could be explored further as ECM substitutes for the regeneration of esophageal tissue.
Fujita, Yuji; Naruto, Takuya; Kohmoto, Tomohiro; Miyakami, Yuko; Watanabe, Miki; Kudo, Yasusei; Fujiwara, Hitoshi; Ichikawa, Daisuke; Otsuji, Eigo; Imoto, Issei
T-cell intracellular antigen-1 (TIA1) is an RNA-binding protein involved in many regulatory aspects of mRNA metabolism. Here, we report previously unknown tumor-promoting activity of TIA1, which seems to be associated with its isoform-specific molecular distribution and regulation of a set of cancer-related transcripts, in esophageal squamous cell carcinoma (ESCC). Immunohistochemical overexpression of TIA1 ectopically localized in the cytoplasm of tumor cells was an independent prognosticator for worse overall survival in a cohort of 143 ESCC patients. Knockdown of TIA1 inhibited proliferation of ESCC cells. By exogenously introducing each of two major isoforms, TIA1a and TIA1b, only TIA1a, which was localized to both the nucleus and cytoplasm, promoted anchorage-dependent and anchorage-independent ESCC cell proliferation. Ribonucleoprotein immunoprecipitation, followed by microarray analysis or massive-parallel sequencing, identified a set of TIA1-binding mRNAs, including SKP2 and CCNA2. TIA1 increased SKP2 and CCNA2 protein levels through the suppression of mRNA decay and translational induction, respectively. Our findings uncover a novel oncogenic function of TIA1 in esophageal tumorigenesis, and implicate its use as a marker for prognostic evaluation and as a therapeutic target in ESCC. PMID:26958940
Bryson, J Barney; Machado, Carolina Barcellos; Crossley, Martin; Stevenson, Danielle; Bros-Facer, Virginie; Burrone, Juan; Greensmith, Linda; Lieberam, Ivo
Damage to the central nervous system caused by traumatic injury or neurological disorders can lead to permanent loss of voluntary motor function and muscle paralysis. Here, we describe an approach that circumvents central motor circuit pathology to restore specific skeletal muscle function. We generated murine embryonic stem cell-derived motor neurons that express the light-sensitive ion channel channelrhodopsin-2, which we then engrafted into partially denervated branches of the sciatic nerve of adult mice. These engrafted motor neurons not only reinnervated lower hind-limb muscles but also enabled their function to be restored in a controllable manner using optogenetic stimulation. This synthesis of regenerative medicine and optogenetics may be a successful strategy to restore muscle function after traumatic injury or disease.
Shin, Sung Yul; Kim, Jung Yoon; Lee, Sanghyeop; Lee, Junwon; Kim, Seung-Jong; Kim, ChangHwan
The purpose of this paper is to propose a new assessment method for evaluating motor function of the patients who are suffering from physical weakness after stroke, incomplete spinal cord injury (iSCI) or other diseases. In this work, we use a robotic device to obtain the information of interaction occur between patient and robot, and use it as a measure for assessing the patients. The Intentional Movement Performance Ability (IMPA) is defined by the root mean square of the interactive torque, while the subject performs given periodic movement with the robot. IMPA is proposed to quantitatively determine the level of subject's impaired motor function. The method is indirectly tested by asking the healthy subjects to lift a barbell to disturb their motor function. The experimental result shows that the IMPA has a potential for providing a proper information of the subject's motor function level.
BACKGROUND: Manganese (Mn) inhalation has been associated with neuropsychological and neurological sequelae in exposed workers. Few environmental epidemiologic studies have examined the potentialy neurotoxic effects of Mn exposure in ambient air on motor function and han...
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
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.
Park, Eun-Young; Kim, Won-Ho
[Purpose] This study aimed to investigate the prevalence of secondary impairments in adults with cerebral palsy. [Subjects and Methods] The study sample included 52 adults with cerebral palsy who attended a convalescent or rehabilitation center for disabled individuals or a special school for physical disabilities in South Korea. [Results] The univariate analysis showed that the Gross Motor Functional Classification System level was a significant predictor of spondylopathies, general pain, arthropathies, and motor ability loss. The prevalence of these impairments at Gross Motor Functional Classification System level I and II was low compared with the prevalence found at Gross Motor Functional Classification System level III–V. The prevalence of secondary impairments among adults with cerebral palsy at Gross Motor Functional Classification System level III–V was high: loss of motor ability, 42.3%; spondylopathies, 38.4%; general pain, 32.7%; and arthropathies, 28.8%. [Conclusion] In this study, adults with severe cerebral palsy showed a high prevalence of motor ability loss, spondylopathies, arthropathies, and pain. It is necessary to develop intervention programs to prevent secondary impairments in adults with cerebral palsy. PMID:28265154
Wang, Zhuo; Guo, Yumei; Myers, Kalisa G.; Heintz, Ryan; Peng, Yu-Hao; Maarek, Jean-Michel I.; Holschneider, Daniel P.
Few studies have examined changes in functional connectivity after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise on the resting-state functional connectivity (rsFC) of motor circuits of rats subjected to bilateral 6-hydroxydopamine lesion of the dorsal striatum. Our results showed substantial similarity between lesion-induced changes in rsFC in the rats and alterations in rsFC reported in Parkinson’s disease subjects, including disconnection of the dorsolateral striatum. Exercise in lesioned rats resulted in: (a) normalization of many of the lesion-induced alterations in rsFC, including reintegration of the dorsolateral striatum into the motor network; (b) emergence of the ventrolateral striatum as a new broadly connected network hub; (c) increased rsFC among the motor cortex, motor thalamus, basal ganglia, and cerebellum. Our results showed for the first time that long-term exercise training partially reversed lesion-induced alterations in rsFC of the motor circuits, and in addition enhanced functional connectivity in specific motor pathways in the Parkinsonian rats, which could underlie recovery in motor functions observed in these rats. PMID:25219465
Wang, Zhuo; Guo, Yumei; Myers, Kalisa G; Heintz, Ryan; Peng, Yu-Hao; Maarek, Jean-Michel I; Holschneider, Daniel P
Few studies have examined changes in functional connectivity after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise on the resting-state functional connectivity (rsFC) of motor circuits of rats subjected to bilateral 6-hydroxydopamine lesion of the dorsal striatum. Our results showed substantial similarity between lesion-induced changes in rsFC in the rats and alterations in rsFC reported in Parkinson's disease subjects, including disconnection of the dorsolateral striatum. Exercise in lesioned rats resulted in: (1) normalization of many of the lesion-induced alterations in rsFC, including reintegration of the dorsolateral striatum into the motor network; (2) emergence of the ventrolateral striatum as a new broadly connected network hub; and (3) increased rsFC among the motor cortex, motor thalamus, basal ganglia, and cerebellum. Our results showed for the first time that long-term exercise training partially reversed lesion-induced alterations in rsFC of the motor circuits, and in addition enhanced functional connectivity in specific motor pathways in the parkinsonian rats, which could underlie recovery in motor functions observed in these animals.
Park, Eun-Young; Kim, Won-Ho
[Purpose] This study aimed to investigate the prevalence of secondary impairments in adults with cerebral palsy. [Subjects and Methods] The study sample included 52 adults with cerebral palsy who attended a convalescent or rehabilitation center for disabled individuals or a special school for physical disabilities in South Korea. [Results] The univariate analysis showed that the Gross Motor Functional Classification System level was a significant predictor of spondylopathies, general pain, arthropathies, and motor ability loss. The prevalence of these impairments at Gross Motor Functional Classification System level I and II was low compared with the prevalence found at Gross Motor Functional Classification System level III-V. The prevalence of secondary impairments among adults with cerebral palsy at Gross Motor Functional Classification System level III-V was high: loss of motor ability, 42.3%; spondylopathies, 38.4%; general pain, 32.7%; and arthropathies, 28.8%. [Conclusion] In this study, adults with severe cerebral palsy showed a high prevalence of motor ability loss, spondylopathies, arthropathies, and pain. It is necessary to develop intervention programs to prevent secondary impairments in adults with cerebral palsy.
SYSTEM FUNCTION DURING ViSUAL-MOTOR PERFORMANCE ___________________________ 12 PERSONAL AUTHOR(S) IIB traP.DGJ cumr Ph.D., T.W. Dushenko. Ph.D. and J.C...monitoring as a means of identifying central nervous system correlates of performance and C-force effects during military flight operations. Four studies...CLASSIFICATION OP -HIS PAGE All other edrtiont are obsl.Oete. Neasuremtent and Modification of Sansorimotor System Function During Visual-Motor Performance
Pathologies that involve the structure and/or function of the esophagus can be life-threatening. The esophagus is a complex organ comprising nonredundant tissue that does not have the ability to regenerate. Currently available interventions for esophageal pathology have limited success and are typically associated with significant morbidity. Hence, there is currently an unmet clinical need for effective methods of esophageal repair. The present article presents a review of esophageal disease along with the anatomic and functional consequences of each pathologic process, the shortcomings associated with currently available therapies, and the latest advancements in the field of regenerative medicine with respect to strategies for esophageal repair from benchtop to bedside. PMID:25813694
Jang, Sung Ho; Kwon, Yong Hyun; Lee, Mi Young; Lee, Dong Yeop; Hong, Ji Heon
Difference of neural connectivity for motor function had been studied by observation of neural activity within gray matter and nucleus using functional neuroimaging techniques. Diffusion tensor imaging (DTI) by a probabilistic tracking is useful for exploration of structural connectivity in the brain. We attempted to investigate difference of neural connectivity for motor function of the affected hand in chronic hemiparetic patients with intracerebral hemorrhage (ICH). Forty-four patients with ICH and 31 normal control subjects were recruited. Diffusion tensor imaging was acquired using a sensitivity-encoding head coil at 1.5 T. Motor function was evaluated using the motricity index (MI) for hand and Modified Brunnstrom Classification (MBC). The presence or absence of a connection was confirmed between the precentral knob of the affected hemisphere and seven areas. Compared with healthy subjects, the patient group showed lower connectivity to the contralesional primary motor cortex, ipsilesional basal ganglia, ipsilesional thalamus, contralesional cerebellum, and ipsilesional medullary pyramid in the affected hemisphere (p<0.05). Connections to the ipsilesional basal ganglia, ipsilesional thalamus, and ipsilesional medullary pyramid showed positive correlation with MI and MBC (p<0.05). We found difference of neural connectivity for motor function between chronic hemiparetic patients with ICH and control subjects. Our results suggest that the motor function of the stroke patient is related to neural connectivity between the ipsilesional M1 and the ipsilesional medullary pyramid, ipsilesional basal ganglia, and ipsilesional thalamus.
Wang, Li; Xing, Jie; Cheng, Rui; Shao, Ying; Li, Peng; Zhu, Shengtao; Zhang, Shutian
Esophageal cancer is one of the most common malignant cancers worldwide. The molecular mechanism of esophageal squamous cell carcinoma (ESCC) is still poorly understood. ESE3 is a member of the Ets transcription family, which is only expressed in epithelial tissues and acts as a tumor suppressor gene in prostate cancer. Our study aim was to confirm whether ESE3 is involved in the carcinogenesis of ESCC. Immunohistochemical analysis revealed that ESE3 was mainly located in cell nuclei of normal tissues and the cytoplasm in ESCC tissues. Immunofluorescence and western blot analyses of the normal esophageal cell line HEEpiC and ESCC cell lines EC9706 TE-1, KYSE150, and KYSE410 confirmed these results. pEGFP-ESE3 and pcDNA3.1-V5/HisA-ESE3 plasmids were constructed for overexpression of ESE3 in EC9706 and KYSE150 cells. The stably transfected cells showed restoration of the nuclear localization of ESE3. EC9706 cells with re-localization of ESE3 to the nucleus showed inhibition of proliferation, colony formation, migration, and invasion. To explore the possible mechanism of the differences in localization of ESE3 in normal esophageal cells and ESCC cells, ESCC cell lines were treated with the nuclear export inhibitor leptomycin B, transcription inhibitor actinomycin D, PKC inhibitor sphinganine, P38 MAPK inhibitor SB202190, and CK II inhibitor TBCA. These reagents were chosen according to the well-known mechanisms of protein translocation. However, the localization of ESE3 was unchanged after these treatments. The sequence of ESE3 cDNA in ESCC cells was identical to the standard sequence of ESE3 in the NCBI Genebank database, indicating that there was no mutation in the coding region of ESE3 in ESCC. Taken together, our study suggests that ESE3 plays an important role in the carcinogenesis of ESCC through changes in subcellular localization and may act as a tumor suppressor gene in ESCC, although the mechanisms require further study.
Souza, Rhonda F
Reflux esophagitis causes Barrett's metaplasia, an abnormal esophageal mucosa predisposed to adenocarcinoma. Medical therapy for reflux esophagitis focuses on decreasing gastric acid production with proton pump inhibitors. We have reported that reflux esophagitis in a rat model develops from a cytokine-mediated inflammatory injury, not from a caustic chemical (acid) injury. In this model, refluxed acid and bile stimulate the release of inflammatory cytokines from esophageal squamous cells, recruiting lymphocytes first to the submucosa and later to the luminal surface. Emerging studies on acute reflux esophagitis in humans support this new concept, suggesting that reflux-induced cytokine release may be a future target for medical therapies. Sometimes, reflux esophagitis heals with Barrett's metaplasia, a process facilitated by reflux-related nitric oxide (NO) production and Sonic Hedgehog (Hh) secretion by squamous cells. We have shown that NO reduces expression of genes that promote a squamous cell phenotype, while Hh signaling induces genes that mediate the development of the columnar cell phenotypes of Barrett's metaplasia. Agents targeting esophageal NO production or Hh signaling conceivably could prevent the development of Barrett's esophagus. Persistent reflux promotes cancer in Barrett's metaplasia. We have reported that acid and bile salts induce DNA damage in Barrett's cells. Bile salts also cause NF-x03BA;B activation in Barrett's cells, enabling them to resist apoptosis in the setting of DNA damage and likely contributing to carcinogenesis. Oral treatment with ursodeoxycholic acid prevents the esophageal DNA damage and NF-x03BA;B activation induced by toxic bile acids. Altering bile acid composition might be another approach to cancer prevention.
Sukal-Moulton, Theresa; de Campos, Ana Carolina; Stanley, Christopher J.; Damiano, Diane L.
There are several advantages that functional near-infrared spectroscopy (fNIRS) presents in the study of the neural control of human movement. It is relatively flexible with respect to participant positioning and allows for some head movements during tasks. Additionally, it is inexpensive, light weight, and portable, with very few contraindications to its use. This presents a unique opportunity to study functional brain activity during motor tasks in individuals who are typically developing, as well as those with movement disorders, such as cerebral palsy. An additional consideration when studying movement disorders, however, is the quality of actual movements performed and the potential for additional, unintended movements. Therefore, concurrent monitoring of both blood flow changes in the brain and actual movements of the body during testing is required for appropriate interpretation of fNIRS results. Here, we show a protocol for the combination of fNIRS with muscle and kinematic monitoring during motor tasks. We explore gait, a unilateral multi-joint movement (cycling), and two unilateral single-joint movements (isolated ankle dorsiflexion, and isolated hand squeezing). The techniques presented can be useful in studying both typical and atypical motor control, and can be modified to investigate a broad range of tasks and scientific questions. PMID:25548919
Buijink, Arthur W G; van der Stouwe, A M Madelein; Broersma, Marja; Sharifi, Sarvi; Groot, Paul F C; Speelman, Johannes D; Maurits, Natasha M; van Rootselaar, Anne-Fleur
Although involvement of the cerebello-thalamo-cortical network has often been suggested in essential tremor, the source of oscillatory activity remains largely unknown. To elucidate mechanisms of tremor generation, it is of crucial importance to study the dynamics within the cerebello-thalamo-cortical network. Using a combination of electromyography and functional magnetic resonance imaging, it is possible to record the peripheral manifestation of tremor simultaneously with brain activity related to tremor generation. Our first aim was to study the intrinsic activity of regions within the cerebello-thalamo-cortical network using dynamic causal modelling to estimate effective connectivity driven by the concurrently recorded tremor signal. Our second aim was to objectify how the functional integrity of the cerebello-thalamo-cortical network is affected in essential tremor. We investigated the functional connectivity between cerebellar and cortical motor regions showing activations during a motor task. Twenty-two essential tremor patients and 22 healthy controls were analysed. For the effective connectivity analysis, a network of tremor-signal related regions was constructed, consisting of the left primary motor cortex, premotor cortex, supplementary motor area, left thalamus, and right cerebellar motor regions lobule V and lobule VIII. A measure of variation in tremor severity over time, derived from the electromyogram, was included as modulatory input on intrinsic connections and on the extrinsic cerebello-thalamic connections, giving a total of 128 models. Bayesian model selection and random effects Bayesian model averaging were used. Separate seed-based functional connectivity analyses for the left primary motor cortex, left supplementary motor area and right cerebellar lobules IV, V, VI and VIII were performed. We report two novel findings that support an important role for the cerebellar system in the pathophysiology of essential tremor. First, in the effective
Mallela, Arka N; Peck, Kyung K; Petrovich-Brennan, Nicole M; Zhang, Zhigang; Lou, William; Holodny, Andrei I
To examine the functional connectivity of the primary and supplementary motor areas (SMA) in glioma patients using resting-state functional MRI (rfMRI). To correlate rfMRI data with tumor characteristics and clinical information to characterize functional reorganization of resting-state networks (RSN) and the limitations of this method. This study was IRB approved and in compliance with Health Insurance Portability and Accountability Act. Informed consent was waived in this retrospective study. We analyzed rfMRI in 24 glioma patients and 12 age- and sex-matched controls. We compared global activation, interhemispheric connectivity, and functional connectivity in the hand motor RSNs using hemispheric voxel counts, pairwise Pearson correlation, and pairwise total spectral coherence. We explored the relationship between tumor grade, volume, location, and the patient's clinical status to functional connectivity. Global network activation and interhemispheric connectivity were reduced in gliomas (p < 0.05). Functional connectivity between the bilateral motor cortices and the SMA was reduced in gliomas (p < 0.01). High-grade gliomas had lower functional connectivity than low-grade gliomas (p < 0.05). Tumor volume and distance to ipsilateral motor cortex demonstrated no association with functional connectivity loss. Functional connectivity loss is associated with motor deficits in low-grade gliomas, but not in high-grade gliomas. Global reduction in resting-state connectivity in areas distal to tumor suggests that radiological tumor boundaries underestimate areas affected by glioma. Association between motor deficits and rfMRI suggests that rfMRI may accurately reflect functional changes in low-grade gliomas. Lack of association between rfMRI and clinical motor deficits implies decreased sensitivity of rfMRI in high-grade gliomas, possibly due to neurovascular uncoupling.
O'Donovan, M J
The field of developmental neurobiology is entering a very exciting phase, in which the application of new techniques promises to lead to major advances in our understanding of basic developmental processes. There is a need to apply much of this new knowledge to problems of spinal cord and muscle development, about which little is known at present. An understanding of the development of muscle fiber types and the spinal circuitry controlling locomotion would have a major impact on fundamental problems in motor control and exercise physiology. Significant progress is likely to be made in these areas in the next few years, but only if researchers interested in motor control and related areas take an interest in development. Among the most immediate problems that need to be addressed are: the lineage analysis of spinal neurons; identification of the factors controlling neuron differentiation; identification of the molecular basis for directed axon growth; and analysis of the factors controlling network assembly in the spinal cord. In muscle development, an understanding of how fiber type proportions are generated would have great significance for disciplines related to motor performance. The interaction and exchange of ideas between developmental biologists and exercise scientists promises to accelerate understanding and progress in both fields of endeavor.
Objective: Exposure to elevated levels of manganese (Mn) may be associated with tremor, motor and executive dysfunction (EF), clinically resembling Parkinson’s disease (PD). PD research has identified tremor-dominant (TD) and non-tremor dominant (NTD) profiles. NTD PD presents with bradykinesia, rigidity, and postural sway, and is associated with EF impairment with lower quality of life (QoL). Presence and impact of tremor, motor, and executive dysfunction profiles on health-related QoL and life satisfaction were examined in air-Mn exposed residents of two Ohio, USA towns. Participants and Methods: From two Ohio towns exposed to air-Mn, 186 residents (76 males) aged 30-75 years were administered measures of EF (Animal Naming, ACT, Rey-O Copy, Stroop Color-Word, and Trails B), motor and tremor symptoms (UPDRS), QoL (BRFSS), life satisfaction (SWLS), and positive symptom distress (SCL-90-R). Air-Mn exposure in the two towns was modeled with 10 years of air-monitoring data. Cluster analyses detected the presence of symptom profiles by grouping together residents with similar scores on these measures. Results: Overall, mean air-Mn concentration for the two towns was 0.53 µg/m3 (SD=.92). Two-step cluster analyses identified TD and NTD symptom profiles. Residents in the NTD group lacked EF impairment; EF impairment represented a separate profile. An unimpaired group also emerged. The NTD and EF impairment groups were qualitatively similar, with relatively lo
Plotnikova, S I; Sviderskiĭ, V L; Gorelkin, V S
The work considers the structural-functional relations existing in the motor neuropil of thoracic ganglia of dragonflies - the animals able to perform very complex and fast maneuvers in the flight. The motor neuropil in dragonflies is shown to be more differentiated than in the lees mobile insects, while motor nuclei in neuropil are more clearly outlined and closer to each other. There are revealed dendrites of motoneurons of pedal muscles (the middle nucleus), which are running into the anterior and posterior nuclei that contain dendrites of motoneurons of wing muscles. A possible role of such approaching is discussed for close functional interaction of wing and foot muscles, which is necessary to dragonflies during flight at their catching of large insects with aid of legs. Peculiarities are considered in structural organization of motoneurons of wing muscles dragonflies and locusts, which indicate the greater functional possibilities peculiar to motoneurons of the dragonflies motor apparatus.
Burunat, Iballa; Brattico, Elvira; Puoliväli, Tuomas; Ristaniemi, Tapani; Sams, Mikko; Toiviainen, Petri
Musical training leads to sensory and motor neuroplastic changes in the human brain. Motivated by findings on enlarged corpus callosum in musicians and asymmetric somatomotor representation in string players, we investigated the relationship between musical training, callosal anatomy, and interhemispheric functional symmetry during music listening. Functional symmetry was increased in musicians compared to nonmusicians, and in keyboardists compared to string players. This increased functional symmetry was prominent in visual and motor brain networks. Callosal size did not significantly differ between groups except for the posterior callosum in musicians compared to nonmusicians. We conclude that the distinctive postural and kinematic symmetry in instrument playing cross-modally shapes information processing in sensory-motor cortical areas during music listening. This cross-modal plasticity suggests that motor training affects music perception. PMID:26422790
van Leeuwen, Thomas; Gan, Jefri; Kistemaker, Jos C M; Pizzolato, Stefano F; Chang, Mu-Chieh; Feringa, Ben L
Molecular switches, rotors, and motors play an important role in the development of nano-machines and devices, as well as responsive and adaptive functional materials. For unidirectional rotors based on chiral overcrowded alkenes, their stereochemical homogeneity is of crucial importance. Herein, a method to obtain new and functionalizable overcrowded alkenes in enantiopure form is presented. The procedure involves a short synthesis of three steps and a solvent-switchable chiral resolution by using a readily available resolving agent. X-ray crystallography revealed the mode of binding of the motor with the resolving agent, as well as the absolute configuration of the motor. (1) H NMR and UV/Vis spectroscopy techniques were used to determine the dynamic behavior of this molecular motor. This method provides rapid access to ample amounts of enantiopure molecular motors, which will greatly facilitate the further development of responsive molecular systems based on chiral overcrowded alkenes.
Cubo, Esther; López Peña, María Jesús; Diez-Feijo Varela, Elio; Pérez Gil, Olga; Garcia Gutierrez, Pablo; Araus González, Elena; Prieto Tedejo, Rosa; Mariscal Pérez, Natividad; Armesto, Diana
Visual symptoms are common among the nonmotor symptoms in Parkinson’s disease. The aims of this study were to assess the diagnostic accuracy and relationship of retinal morphologic and functional changes with motor and non-motor symptoms disturbances in Parkinson’s disease. Thirty patients with Parkinson’s disease, with a median Hoehn-Yahr stage of 2 (1-4), were compared to 30 age- and gender-matched controls. Retinal thinning and function were measured using optical coherence tomography (OCT), visual evoked potentials (VEP), and pattern electroretinography. Motor impairment and motor laterality were measured using the Short Parkinson’s Evaluation Scale/Scales for Outcomes in Parkinson’s disease, and non-motor symptoms severity using the nonmotor symptoms questionnaire. Only pattern electroretinography, P50 and N95 amplitudes, were lower in patients with Parkinson’s disease, compared to controls (p = 0.01, respectively). Age, disease duration, levodopa dose, motor, and non-motor impairment were not significantly associated with retinal thinning and functional changes. The patients vs. controls area under the curve of OCT, VEP, and pattern electroretinography receiver-operating-characteristic curves were<0.50. In conclusion, morphologic and functional retina changes are not significantly correlated with motor and non-motor symptoms impairment severity, and do not discriminate between Parkinson’s disease and controls.
Scheerens, Charlotte; Tack, Jan; Rommel, Nathalie
Ineffective esophageal motility (IEM) is the most frequently encountered esophageal motility disorder. Patients may present with a variety of symptoms, such as dysphagia, heartburn, odynophagia, and regurgitation. Over the past years, the landscape of esophageal motility testing has been revolutionized; however, our current treatment options for IEM still remain limited. Previous studies have suggested that buspirone, a serotonin receptor agonist, enhances esophageal peristalsis and lower esophageal sphincter (LES) function. Recent work provides the first evidence that buspirone may influence LES resting pressure in patients with systemic sclerosis. Future research should evaluate whether the beneficial effects of buspirone also apply to the broad clinical entity of esophageal dysphagia patients with IEM.
Suzuki, Toshiaki; Bunno, Yoshibumi; Onigata, Chieko; Tani, Makiko; Uragami, Sayuri; Yoshida, Sohei
the median nerve at the wrist in subjects during two motor imagery conditions: holding and not holding the sensor of a pinch meter between the thumb and index finger. Our aim was to determine whether mental simulation without the muscle contraction associated with motion can increase the excitability of spinal neural function in patients with Parkinson's disease (PD). F-waves of the left thenar muscles were examined in 10 patients with PD under resting, holding and motor imagery conditions. For the holding condition, the subjects held the sensor of the pinch meter between their thumb and index finger. For the motor imagery conditions, the subjects were asked to imagine a 50% maximal voluntary isometric contraction holding and not holding the sensor of the pinch meter between their thumb and index finger (motor imagery "with"/"without sensor"). Persistence during motor imagery under the "with sensor" condition increased significantly compared with persistence during resting (n=10, z=2.2509, p=0.0244, Wilcoxon test). The F/M amplitude ratio during motor imagery under the "with sensor" condition increased significantly compared with that during resting (n=10, z=2.1915, p=0.0284, Wilcoxon test). Excitability of spinal neural function during motor imagery in Parkinson's disease Motor imagery under the "with the sensor" condition increased excitability of the spinal neural output to the thenar muscles. Because excitability of the spinal neural output to the thenar muscles during motor imagery "with the sensor" was significantly higher than that during resting, we suggest that movement preparation for a motor imagery task is important in patients with PD.
Nam, Ki Seok
[Purpose] This observational study provides a retrospective description of changes in motor function of a 10 year old child who suffered from motor weakness caused by Moyamoya disease (MMD) over an approximately 3 year follow-up observation period. [Methods] The child was diagnosed as MMD due to multifocal encephalomalacia in both frontal and parietal cortices. After the ischemic attack, the child received physical therapy the based on stroke rehabilitation, including muscle strengthening exercises, training of functional activity/ADL, and neurodevelopmental treatment. [Results] The child's MRI showed areas of ischemic infarction in both the frontal and parietal lobes. Steno-occlusive findings for both the anterior cerebral artery and middle cerebral artery were observed on cerebral angiography. Regarding changes of motor function during the three-year follow-up, significant improvements, in the Motricity index, Modified Brunnstrom Classification, manual function test, and functional ambulatory category were observed. [Conclusion] The basic motor function and functional abilities of the child showed improvement with conservative treatment over approximately three years. The functional motor ability of children with MMD may be similar to the recovery progression of pediatric stroke patients, if there is no re-occurrence of ischemia.
Casartelli, Luca; Molteni, Massimo; Ronconi, Luca
Difficulties in the social domain and motor anomalies have been widely investigated in Autism Spectrum Disorder (ASD). However, they have been generally considered as independent, and therefore tackled separately. Recent advances in neuroscience have hypothesized that the cortical motor system can play a role not only as a controller of elementary physical features of movement, but also in a complex domain as social cognition. Here, going beyond previous studies on ASD that described difficulties in the motor and in the social domain separately, we focus on the impact of motor mechanisms anomalies on social functioning. We consider behavioral, electrophysiological and neuroimaging findings supporting the idea that motor cognition is a critical "intermediate phenotype" for ASD. Motor cognition anomalies in ASD affect the processes of extraction, codification and subsequent translation of "external" social information into the motor system. Intriguingly, this alternative "motor" approach to the social domain difficulties in ASD may be promising to bridge the gap between recent experimental findings and clinical practice, potentially leading to refined preventive approaches and successful treatments.
Bender, Stephan; Rellum, Thomas; Freitag, Christine; Resch, Franz; Rietschel, Marcella; Treutlein, Jens; Jennen-Steinmetz, Christine; Brandeis, Daniel; Banaschewski, Tobias; Laucht, Manfred
Background Dopamine plays an important role in orienting, response anticipation and movement evaluation. Thus, we examined the influence of functional variants related to dopamine inactivation in the dopamine transporter (DAT1) and catechol-O-methyltransferase genes (COMT) on the time-course of motor processing in a contingent negative variation (CNV) task. Methods 64-channel EEG recordings were obtained from 195 healthy adolescents of a community-based sample during a continuous performance task (A-X version). Early and late CNV as well as motor postimperative negative variation were assessed. Adolescents were genotyped for the COMT Val158Met and two DAT1 polymorphisms (variable number tandem repeats in the 3′-untranslated region and in intron 8). Results The results revealed a significant interaction between COMT and DAT1, indicating that COMT exerted stronger effects on lateralized motor post-processing (centro-parietal motor postimperative negative variation) in homozygous carriers of a DAT1 haplotype increasing DAT1 expression. Source analysis showed that the time interval 500–1000 ms after the motor response was specifically affected in contrast to preceding movement anticipation and programming stages, which were not altered. Conclusions Motor slow negative waves allow the genomic imaging of dopamine inactivation effects on cortical motor post-processing during response evaluation. This is the first report to point towards epistatic effects in the motor system during response evaluation, i.e. during the post-processing of an already executed movement rather than during movement programming. PMID:22649558
Küker, W; Friese, S; Riethmüller, J; Krägeloh-Mann, I
Congenital bilateral perisylvian syndrome (CBPS) is a syndrome of cortical malformation characterized by faciopharyngoglossomasticatory diplegia. We report on two cases of CBPS with associated esophageal malformations and a poor mental and motor development. The association of CBPS and esophageal malformations may indicate a subgroup of patients with a very early prenatal injury, characterised by a bad prognosis due to severe cortical disorganization. However, it can not be excluded that the association of CBPS and esophageal malformation is purely coincidental.
Harel, Yael; Zuk, Luba; Guindy, Michal; Nakar, Orly; Lotan, Dafna; Fattal-Valevski, Aviva
We investigated the long-term implications of infantile thiamine (vitamin B1) deficiency on motor function in preschoolers who had been fed during the first 2 years of life with a faulty milk substitute. In this retrospective cohort study, 39 children aged 5-6 years who had been exposed to a thiamine-deficient formula during infancy were compared with 30 age-matched healthy children with unremarkable infant nutritional history. The motor function of the participants was evaluated with The Movement Assessment Battery for Children (M-ABC) and the Zuk Assessment. Both evaluation tools revealed statistically significant differences between the exposed and unexposed groups for gross and fine motor development (p < .001, ball skills p = .01) and grapho-motor development (p = .004). The differences were especially noteworthy on M-ABC testing for balance control functioning (p < .001, OR 5.4; 95% CI 3.4-7.4) and fine motor skills (p < .001, OR 3.2; 95% CI 1.8-4.6). In the exposed group, both assessments concurred on the high rate of children exhibiting motor function difficulties in comparison to unexposed group (M-ABC: 56% vs. 10%, Zuk Assessment: 59% vs. 3%, p < .001). Thiamine deficiency in infancy has long-term implications on gross and fine motor function and balance skills in childhood, thiamine having a crucial role in normal motor development. The study emphasizes the importance of proper infant feeding and regulatory control of breast milk substitutes.
Lotz, Leslie; Loxton, Helene; Naidoo, Anthony V
Visual-motor integration functioning has been identified as playing an integral role in different aspects of a child's development. Sensory-motor development is not only foundational to the physical maturation process, but is also imperative for progress with formal learning activities. Deficits in visual-motor integration have been identified as precursors of later learning disabilities and other neurological conditions. The primary aim of this study was to determine the status of visual-motor integration functioning of a group of learners from a disadvantaged peri-urban South African community. Visual-motor integration functioning was assessed using the Developmental Test of Visual-Motor Integration (VMI) and the Goodenough-Harris Drawing Test (GHD). Three hundred and thirty-nine learners in grades 1-4 were assessed and results for the group relative to gender, chronological age and socioeconomic status are reported. For the group, the mean test age fell 16 months below the mean chronological age on the VMI. The mean GHD score for the group was about a half a standard deviation below the GHD's test norm. At school entry level, visual-motor integration was more than one standard deviation below the mean. Compared to female learners, male learners achieved significantly higher scores on the test age score of the VMI (mean difference = 8.69 months), and the intelligence coefficient score of the GHD (mean difference = 4.68). Scores on both measures increased as a function of socioeconomic status. The VMI and GHD scores were significantly correlated (r = 0.45; P < 0.01) suggesting that visual-motor integration is integral to intellectual functioning.
Corti, Emily J; Johnson, Andrew R; Riddle, Hayley; Gasson, Natalie; Kane, Robert; Loftus, Andrea M
The present study examined the relationship between executive function (EF) and fine motor control in young and older healthy adults. Participants completed 3 measures of executive function; a spatial working memory (SWM) task, the Stockings of Cambridge task (planning), and the Intra-Dimensional Extra-Dimensional Set-Shift task (set-shifting). Fine motor control was assessed using 3 subtests of the Purdue Pegboard (unimanual, bimanual, sequencing). For the younger adults, there were no significant correlations between measures of EF and fine motor control. For the older adults, all EFs significantly correlated with all measures of fine motor control. Three separate regressions examined whether planning, SWM and set-shifting independently predicted unimanual, bimanual, and sequencing scores for the older adults. Planning was the primary predictor of performance on all three Purdue subtests. A multiple-groups mediation model examined whether planning predicted fine motor control scores independent of participants' age, suggesting that preservation of planning ability may support fine motor control in older adults. Planning remained a significant predictor of unimanual performance in the older age group, but not bimanual or sequencing performance. The findings are discussed in terms of compensation theory, whereby planning is a key compensatory resource for fine motor control in older adults.
Ross, Christopher A.; Pantelyat, Alex; Kogan, Jane; Brandt, Jason
The clinical syndrome of Huntington’s disease is notable for a triad of motor, cognitive and emotional features. All HD patients eventually become occupationally disabled; however the factors that render HD patients unable to maintain employment have not been extensively studied. This review begins by discussing the clinical triad of HD, highlighting the distinction in the motor disorder between involuntary movements such as chorea, and voluntary movement impairment, with the latter contributing more to functional disability. Cognitive disorder clearly contributes to disability, though the relative contribution compared to motor is difficult to unravel, especially since many of the tests used to asses “cognition” have a strong motor component. The role of emotional changes in disability needs more study. The literature on contributions to functional disability, driving impairment and nursing home placement is reviewed. Relevant experience is presented from the longstanding JHU HD observational study on motor vs cognitive onset, and on cognitive and motor features at the time when individuals discontinued working. Finally, we briefly review government policies in several countries on disability determination. We interpret the data from our own studies and from the literature to indicate that there is usually a close relationship between cognitive and motor dysfunction, and that it is critical to take both into consideration in determining disability. PMID:25216368
Buchman, Aron S.; Wilson, Robert S.; Leurgans, Sue E.; Bennett, David A.; Barnes, Lisa L.
Objective We tested whether declining motor function accelerates with age in older African Americans. Methods Eleven motor performances were assessed annually in 513 older African Americans. Results During follow-up of 5 years, linear mixed-effect models showed that motor function declined by about 0.03 units/yr (Estimate, −0.026, p<0.001); about 4% more rapidly for each additional year of age at baseline. A proportional hazard model showed that both baseline motor function level and its rate of change were independent predictors of death and incident disability (all p’s <0.001). These models showed that the additional annual amount of motor decline in 85 year old persons at baseline versus 65 year old persons was associated with a 1.5-fold higher rate of death and a 3-fold higher rate of developing Katz disability. Conclusions The rate of declining motor function accelerates with increasing age and its rate of decline predicts adverse health outcomes in older African Americans. PMID:26209439
Moore, Tara L; Killiany, Ronald J; Pessina, Monica A; Moss, Mark B; Rosene, Douglas L
In the elderly, intact motor functions of the upper extremity are critical for the completion of activities of daily living. Many studies have provided insight into age-related changes in motor function. However, the precise nature and extent of motor impairments of the upper extremity remains unclear. In the current study we have modified two tasks to assess hand/digit function in both young and aged rhesus monkeys. We tested monkeys from 9 to 26 years of age on these tasks to determine the level of fine motor performance across the adult age range. Compared to young monkeys (9-12 years of age), aged monkeys (15-26 years of age) were mildly impaired on fine motor control of the digits. These findings are consistent with previous studies that have found age-related impairment in fine motor function. However, the magnitude and extent of impairment in the current study does differ from previous findings and is likely due to methodological differences in the degree of task complexity.
Hummel, Friedhelm C; Heise, Kirstin; Celnik, Pablo; Floel, Agnes; Gerloff, Christian; Cohen, Leonardo G
Healthy ageing is accompanied by limitations in performance of activities of daily living and personal independence. Recent reports demonstrated improvements in motor function induced by noninvasive anodal direct current stimulation (tDCS) of the primary motor cortex (M1) in young healthy adults. Here we tested the hypothesis that a single session of anodal tDCS over left M1 could facilitate performance of right upper extremity tasks required for activities of daily living (Jebsen-Taylor hand function test, JTT) in older subjects relative to Sham in a double-blind cross-over study design. We found (a) significant improvement in JTT function with tDCS relative to Sham that outlasted the stimulation period by at least 30 min, (b) that the older the subjects the more prominent this improvement appeared and (c) that consistent with previous results in younger subjects, these effects were not accompanied by any overt undesired side effect. We conclude that anodal tDCS applied over M1 can facilitate performance of skilled hand functions required for activities of daily living in older subjects.
Murdocca, Michela; Malgieri, Arianna; Luchetti, Andrea; Saieva, Luciano; Dobrowolny, Gabriella; de Leonibus, Elvira; Filareto, Antonio; Quitadamo, Maria Chiara; Novelli, Giuseppe; Musarò, Antonio; Sangiuolo, Federica
Spinal muscular atrophy (SMA) is an inherited neurodegenerative disorder and the first genetic cause of death in childhood. SMA is caused by low levels of survival motor neuron (SMN) protein that induce selective loss of α-motor neurons (MNs) in the spinal cord, resulting in progressive muscle atrophy and consequent respiratory failure. To date, no effective treatment is available to counteract the course of the disease. Among the different therapeutic strategies with potential clinical applications, the evaluation of trophic and/or protective agents able to antagonize MNs degeneration represents an attractive opportunity to develop valid therapies. Here we investigated the effects of IPLEX (recombinant human insulinlike growth factor 1 [rhIGF-1] complexed with recombinant human IGF-1 binding protein 3 [rhIGFBP-3]) on a severe mouse model of SMA. Interestingly, molecular and biochemical analyses of IGF-1 carried out in SMA mice before drug administration revealed marked reductions of IGF-1 circulating levels and hepatic mRNA expression. In this study, we found that perinatal administration of IPLEX, even if does not influence survival and body weight of mice, results in reduced degeneration of MNs, increased muscle fiber size and in amelioration of motor functions in SMA mice. Additionally, we show that phenotypic changes observed are not SMN-dependent, since no significant SMN modification was addressed in treated mice. Collectively, our data indicate IPLEX as a good therapeutic candidate to hinder the progression of the neurodegenerative process in SMA.
Kim, Seong-Gi; Ashe, James; Hendrich, Kristy; Ellermann, Jutta M.; Merkle, Hellmut; Ugurbil, Kamil; Georgopoulos, Apostolos P.
A hemispheric asymmetry in the functional activation of the human motor cortex during contralateral (C) and ipsilateral (I) finger movements, especially in right-handed subjects, was documented with nuclear magnetic resonance imaging at high field strength (4 tesla). Whereas the right motor cortex was activated mostly during contralateral finger movements in both right-handed (C/I mean area of activation = 36.8) and left-handed (C/I = 29.9) subjects, the left motor cortex was activated substantially during ipsilateral movements in left-handed subjects (C/I = 5.4) and even more so in right-handed subjects (C/I = 1.3).
Aleksandrović, Marko; Radovanović, Dragan; Okičić, Tomislav; Madić, Dejan; Georgiev, Georgi
The purpose of this study was to assess the influence of functional abilities on specificmotor skills. A total number of 92 male water polo players (age 12±0.5 years, body height 156.96±22.3 cm, body weight 51.02±33.18 kg) with at least two years’ experience, were enrolled in the study. The investigation protocol consisted of standardized anthropometric measurements, estimation of maximum oxygen uptake, determination of the lung function values, specific swim tests and swim tests with a ball. The factor analysis was used for the estimation of the structure of specific motor skills. The influence of functional abilities on specific motor skills was estimated by regression analysis. Out of 15 correlations in total between the variables of space of functional abilities of water polo players, 6 were significant at the level of 95% (between the variables of aerobic power and lung function) and all of the correlations (15) between the variables of specific motor skills in water polo players were significant at the 99% level. Only one principal component, the General factor of specific motor skills in water polo (GFSWP) was obtained by way of factorization of the tests of specific motor skills, so the GFSWP represents the latent space of specific motor skills as a criterion. The regression analysis showed that functional abilities (as group predictors) (p= 0.00) and forced expiratory volume in 1 second (as a separate variable) have a significant influence on GFSWP (the criterion). The results of the study pointed out the impact of functional abilities on specific motor skills of selected young water polo players. This may be important for the selection and effective coaching in the early period of training and can affect the development of more appropriate and specific training programmes for optimal physical fitness preparation in young water polo players. PMID:23486729
Aleksandrović, Marko; Radovanović, Dragan; Okičić, Tomislav; Madić, Dejan; Georgiev, Georgi
The purpose of this study was to assess the influence of functional abilities on specificmotor skills. A total number of 92 male water polo players (age 12±0.5 years, body height 156.96±22.3 cm, body weight 51.02±33.18 kg) with at least two years' experience, were enrolled in the study. The investigation protocol consisted of standardized anthropometric measurements, estimation of maximum oxygen uptake, determination of the lung function values, specific swim tests and swim tests with a ball. The factor analysis was used for the estimation of the structure of specific motor skills. The influence of functional abilities on specific motor skills was estimated by regression analysis. Out of 15 correlations in total between the variables of space of functional abilities of water polo players, 6 were significant at the level of 95% (between the variables of aerobic power and lung function) and all of the correlations (15) between the variables of specific motor skills in water polo players were significant at the 99% level. Only one principal component, the General factor of specific motor skills in water polo (GFSWP) was obtained by way of factorization of the tests of specific motor skills, so the GFSWP represents the latent space of specific motor skills as a criterion. The regression analysis showed that functional abilities (as group predictors) (p= 0.00) and forced expiratory volume in 1 second (as a separate variable) have a significant influence on GFSWP (the criterion). The results of the study pointed out the impact of functional abilities on specific motor skills of selected young water polo players. This may be important for the selection and effective coaching in the early period of training and can affect the development of more appropriate and specific training programmes for optimal physical fitness preparation in young water polo players.
in esophageal tissue (arrowheads) in WT than IL21R-/- mice (A) is quantified morphometrically in (B). Quantitative PCR (C) for esophageal...microscopy and morphometric analysis was used to measure IL21 receptor expression in patient esophageal biopsies. RESULTS: A number of genetic variants...most highly associated variants in the locus. Immunofluorescent microscopy and morphometric analysis demonstrate a marked increase in IL21 receptor
Dawsey, Sanford M.; Fagundes, Renato B.; Jacobson, Brian C.; Kresty, Laura A.; Mallery, Susan R.; Paski, Shirley; van den Brandt, Piet A.
The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on macronutrients, dietary patterns, and risk of adenocarcinoma in Barrett’s esophagus; micronutrients, trace elements, and risk of Barrett’s esophagus and esophageal adenocarcinoma; the role of mate consumption in the development of squamous cell carcinoma; the relationship between energy excess and development of esophageal adenocarcinoma; and the nutritional management of the esophageal cancer patient. PMID:25266021
Kim, Namhee; Park, Chungoo; Jeong, Yongsu; Song, Mi-Ryoung
Functional diversification of motor neurons has occurred in order to selectively control the movements of different body parts including head, trunk and limbs. Here we report that transcription of Isl1, a major gene necessary for motor neuron identity, is controlled by two enhancers, CREST1 (E1) and CREST2 (E2) that allow selective gene expression of Isl1 in motor neurons. Introduction of GFP reporters into the chick neural tube revealed that E1 is active in hindbrain motor neurons and spinal cord motor neurons, whereas E2 is active in the lateral motor column (LMC) of the spinal cord, which controls the limb muscles. Genome-wide ChIP-Seq analysis combined with reporter assays showed that Phox2 and the Isl1-Lhx3 complex bind to E1 and drive hindbrain and spinal cord-specific expression of Isl1, respectively. Interestingly, Lhx3 alone was sufficient to activate E1, and this may contribute to the initiation of Isl1 expression when progenitors have just developed into motor neurons. E2 was induced by onecut 1 (OC-1) factor that permits Isl1 expression in LMCm neurons. Interestingly, the core region of E1 has been conserved in evolution, even in the lamprey, a jawless vertebrate with primitive motor neurons. All E1 sequences from lamprey to mouse responded equally well to Phox2a and the Isl1-Lhx3 complex. Conversely, E2, the enhancer for limb-innervating motor neurons, was only found in tetrapod animals. This suggests that evolutionarily-conserved enhancers permit the diversification of motor neurons. PMID:26447474
Hanks, J.B.; Fisher, S.R.; Meyers, W.C.; Christian, K.C.; Postlethwait, R.W.; Jones, R.S.
Total laryngectomy for cancer can result in dysphagia and altered esophageal motility. Manometric changes in the upper esophageal sphincter (UES), and in proximal and distal esophageal function have been reported. However, most studies have failed to take into account radiation therapy and appropriate controls. We selected ten male patients (54.3 +/- 1.9 yr) for longitudinal manometric evaluation prior to laryngectomy then at two weeks and again six months later. No patient received preoperative radiation therapy, had a previous history of esophageal surgery, or developed a postoperative wound infection or fistula. Seven of ten patients had positive nodes and received 6,000-6,600 rads postoperative radiation therapy. Preoperatively 4 of 10 patients complained of dysphagia which did not significantly change following surgery and radiation. Two of three patients who did not complain of dysphagia preoperatively and received radiation postoperatively developed dysphagia. No patient without dysphagia preoperatively who received no radiation therapy developed symptoms. Our studies show that laryngectomy causes alterations in the UES resting and peak pressures but not in the proximal or distal esophagus, or the lower esophageal sphincter. These data also imply radiation therapy may be associated with progressive alterations in motility and symptomatology. Further study regarding the effects of radiation on esophageal motility and function are urged.
Agulova, L P; Bol'shakova, N P; Andreevskikh, A V; Suchkova, N G; Kravchenko, L B; Moskvitina, N S
Motor asymmetry of paws was studied in three species of mouse rodents (Apodemus agrarius, Clethrionomys glareolus, Clethrionomys rutilus) from natural populations. The prevalence of right-hand asymmetry was revealed in both males and females of all studied species. The spatial and temporal variability of asymmetry structures was shown. The increased number of left-handed rodents was observed in unfavorable habitats. A possible adaptive role of the functional motor asymmetry exemplified by small rodents is discussed.
Lee, Kyoung Bo; Lim, Seong Hoon; Kim, Young Dong; Yang, Byung Il; Kim, Kyung Hoon; Lee, Kang Sung; Kim, Eun Ja; Hwang, Byong Yong
[Purpose] The aim of this study was to identify the contributions of balance to gait and motor function in chronic stroke. [Subjects and Methods] Twenty-three outpatients participated in a cross-sectional assessment. Gait ability was assessed using the functional ambulation category, self-paced 10-m walking speed, and fastest 10-m walking speed. Standing balance and trunk control measures included the Berg Balance Scale and the Trunk Impairment Scale. Univariate and multivariate regression analyses were performed. [Results] Balance was the best predictor of the FAC, self-paced walking speed, and fastest walking speed, accounting for 57% to 61% of the variances. Additionally, the total score of TIS was the only predictor of the motor function of the lower limbs and the dynamic balance of TIS was a predictor of the motor function of the upper limbs, accounting for 41% and 29% of the variance, respectively. [Conclusion] This study demonstrated the relative contribution of standing balance and trunk balance to gait ability and motor function. They show that balance has a high power of explanation of gait ability and that trunk balance is a determinant of motor function rather than gait ability. PMID:27390395
Lee, Kyoung Bo; Lim, Seong Hoon; Kim, Young Dong; Yang, Byung Il; Kim, Kyung Hoon; Lee, Kang Sung; Kim, Eun Ja; Hwang, Byong Yong
[Purpose] The aim of this study was to identify the contributions of balance to gait and motor function in chronic stroke. [Subjects and Methods] Twenty-three outpatients participated in a cross-sectional assessment. Gait ability was assessed using the functional ambulation category, self-paced 10-m walking speed, and fastest 10-m walking speed. Standing balance and trunk control measures included the Berg Balance Scale and the Trunk Impairment Scale. Univariate and multivariate regression analyses were performed. [Results] Balance was the best predictor of the FAC, self-paced walking speed, and fastest walking speed, accounting for 57% to 61% of the variances. Additionally, the total score of TIS was the only predictor of the motor function of the lower limbs and the dynamic balance of TIS was a predictor of the motor function of the upper limbs, accounting for 41% and 29% of the variance, respectively. [Conclusion] This study demonstrated the relative contribution of standing balance and trunk balance to gait ability and motor function. They show that balance has a high power of explanation of gait ability and that trunk balance is a determinant of motor function rather than gait ability.
Hirsiger, Sarah; Koppelmans, Vincent; Mérillat, Susan; Liem, Franziskus; Erdeniz, Burak; Seidler, Rachael D; Jäncke, Lutz
Age-related behavioral declines may be the result of deterioration of white matter tracts, affecting brain structural (SC) and functional connectivity (FC) during resting state. To date, it is not clear if the combination of SC and FC data could better predict cognitive/motor performance than each measure separately. We probed these relationships in the cingulum bundle, a major white matter pathway of the default mode network. We aimed to attain deeper knowledge about: (a) the relationship between age and the cingulum's SC and FC strength, (b) the association between SC and FC, and particularly (c) how the cingulum's SC and FC are related to cognitive/motor performance separately and combined. We examined these associations in a healthy and well-educated sample of 165 older participants (aged 64-85). SC and FC were acquired using probabilistic tractography to derive measures to capture white matter integrity within the cingulum bundle (fractional anisotropy, mean, axial and radial diffusivity) and a seed-based resting-state functional MRI correlation approach, respectively. Participants performed cognitive tests measuring processing speed, memory and executive functions, and motor tests measuring motor speed and grip force. Our data revealed that only SC but not resting state FC was significantly associated with age. Further, the cingulum's SC and FC showed no relation. Different relationships between cognitive/motor performance and SC/FC separately were found, but no additive effect of the combined analysis of cingulum's SC and FC for predicting cognitive/motor performance was apparent.
Sato, Takatoshi; Adachi, Michiru; Nakamura, Kaho; Zushi, Masaya; Goto, Keisuke; Murakami, Terumi; Ishiguro, Kumiko; Shichiji, Minobu; Saito, Kayoko; Ikai, Tetsuo; Osawa, Makiko; Kondo, Izumi; Nagata, Satoru; Ishigaki, Keiko
Fukuyama congenital muscular dystrophy (FCMD) is the second most common muscular dystrophy in Japan. FCMD is an autosomal recessive disorder caused by mutations in the fukutin gene. The main features of FCMD are a combination of infantile-onset hypotonia, generalized muscle weakness, eye abnormalities, and mental retardation associated with cortical migration defects, and most patients are never able to walk. To date, the development of a quantitative motor scale for FMCD has been difficult due to the moderate-to-severe intellectual impairment that accompanies FCMD. Gross motor function measure (GMFM), originally developed as a quantitative motor scale for cerebral palsy, can precisely and quantitatively assess motor function without complicated instructions, and was recently reported to be useful in the assessment of Down syndrome and spinal muscular atrophy. To confirm the validity of GMFM for the assessment of FCMD, 41 FCMD patients (age range: 0.6-24.4 years) were recruited for this study. The GMFM scores correlated significantly with those of two previously used motor scales, and the time-dependent change in GMFM scores was consistent with the natural course of FCMD. The inter-rater reliability, based on determinations made by four physiotherapists blinded to each other's assessment results, was excellent. We concluded GMFM to be a useful and valid measure of motor function in FCMD patients.
Yan, Li-Rong; Wu, Yi-Bo; Hu, De-Wen; Qin, Shang-Zhen; Xu, Guo-Zheng; Zeng, Xiao-Hua; Song, Hua
There are ample functional magnetic resonance imaging (fMRI) studies on functional brain asymmetries, and the asymmetry of cerebral network in the resting state may be crucial to brain function organization. In this paper, a unified schema of voxel-wise functional connectivity and asymmetry analysis was presented and the network asymmetry of motor areas was studied. Twelve healthy male subjects with mean age 29.8 ± 6.4 were studied. Functional network in the resting state was described by using functional connectivity magnetic resonance imaging (fcMRI) analysis. Motor areas were selected as regions of interest (ROIs). Network asymmetry, including intra- and inter-network asymmetries, was formulated and analyzed. The intra-network asymmetry was defined as the difference between the left and right part of a particular functional network. The inter-network asymmetry was defined as the difference between the networks for a specific ROI in the left hemisphere and its homotopic ROI in the right hemisphere. Primary motor area (M1), primary sensory area (S1) and premotor area (PMA) exhibited higher functional correlation with the right parietal-temporal-occipital circuit and the middle frontal gyrus than they did with the left hemisphere. Right S1 and right PMA exhibited higher functional correlation with the ipsilateral precentral and supramarginal areas. There exist the large-scale hierarchical network asymmetries of the motor areas in the resting state. These asymmetries imply the right hemisphere dominance for predictive motor coding based on spatial attention and higher sensory processing load for the motor performance of non-dominant hemisphere.
Sabirov, A G; Raginov, I S; Burmistrov, M V; Chelyshev, Y A; Khasanov, R Sh; Moroshek, A A; Grigoriev, P N; Zefirov, A L; Mukhamedyarov, M A
We carried out a detailed analysis of rat model of esophageal achalasia previously developed by us. Manifest morphological and functional disorders were observed in experimental achalasia: hyperplasia of the squamous epithelium, reduced number of nerve fibers, excessive growth of fibrous connective tissue in the esophageal wall, high contractile activity of the lower esophageal sphincter, and reduced motility of the longitudinal muscle layer. Changes in rat esophagus observed in experimental achalasia largely correlate with those in esophageal achalasia in humans. Hence, our experimental model can be used for the development of new methods of disease treatment.
Perlman, Amichai; Shah, Raj C.; Bennett, David A.; Buchman, Aron S.; Matok, Ilan
Objectives To investigate whether the use of antihypertensive and statin medication in very old adults is associated with the level of motor performance. Design Cross sectional study. Settings A community-based study recruited from over 40 residential facilities across the metropolitan Chicago area. Participants Community dwelling very old adults (n=1520; mean age 80.2; SD 7.7). Measurements Eleven motor performances were summarized using a composite motor score. All prescription and over the counter medications taken by participants were inspected and coded using the Medi-Span Data Base System. Demographic characteristics and medical history were obtained via detailed interview and medical exams. Results In multiple linear regression models, antihypertensive medications were associated with global motor score (β=−0.075, S.E. 0.011, p<0.001). Thus, motor function in an individual with antihypertensive medication, was on average, about 7.5% lower than an age, sex and education matched individual without antihypertensive medication. The number of antihypertensive medications which were being used had an additive effect, such that a reduction in the level of motor function was observed with each additional medication, and receiving three or more antihypertensive medications was associated with about a 15% reduction in the level of motor function. The association between antihypertensive medications and motor function was robust, and remained unchanged after adjusting for confounding by indication using several potentially confounding variables: smoking, hypertension, diabetes, stroke, congestive heart-failure, myocardial infarction, and intermittent claudication (β=−0.05, S.E. 0.015, p=0.001). In contrast, the use of statin medications was not related to motor function (unadjusted: β=0.003, S.E.=0.015, p=0.826; fully adjusted: β=0.018, S.E. 0.014, p=0.216). Conclusion The use of antihypertensive medications is associated with a lower level of motor function in
Gorges, Martin; Müller, Hans-Peter; Mayer, Isabella Maria Sophie; Grupe, Gesa Sophie; Kammer, Thomas; Grön, Georg; Kassubek, Jan; Landwehrmeyer, G Bernhard; Wolf, Robert Christian; Orth, Michael
Structural and functional changes attributable to the neurodegenerative process in Huntington's disease (HD) may be evident in HTT CAG repeat expansion carriers before the clinical manifestations of HD. It remains unclear, though, how far from motor onset a consistent signature of the neurodegenerative process in HD can be detected. Twelve far from onset preHD and 22 age-matched healthy control participants underwent volumetric structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and resting-state functional MRI (11 preHD, 22 controls) as well as electrophysiological measurements (12 preHD, 13 controls). There were no significant differences in white matter macro- and microstructure between far from onset preHD participants and controls. Functional connectivity in a basal ganglia-thalamic and motor networks, all measures of the motor efferent and sensory afferent pathways as well as sensory-motor integration were also similar in far from onset preHD and controls. With the methods used in far from onset preHD sensory-motor neural macro- or micro-structure and brain function were similar to healthy controls. This suggests that any observable structural and functional change in preHD nearer to onset, or in manifest HD, at least using comparable techniques such as in this study, most likely reflects an ongoing neurodegenerative process.
Alcalay, RN; Caccappolo, E; Mejia-Santana, H; Tang, M–X; Rosado, L; Orbe Reilly, M; Ruiz, D; Louis, ED; Comella, C; Nance, M; Bressman, S; Scott, WK; Tanner, C; Mickel, S; Waters, C; Fahn, S; Cote, L; Frucht, S; Ford, B; Rezak, M; Novak, K; Friedman, JH; Pfeiffer, R; Marsh, L; Hiner, B; Payami, H; Molho, E; Factor, SA; Nutt, J; Serrano, C; Arroyo, M; Ottman, R; Pauciulo, M; Nichols, W; Clark, LN; Marder, K
Importance The long term cognitive outcome in PARKIN-PD patients is unknown. This data may be meaningful when counseling PARKIN-PD patients. Objective Among early-onset PD (EOPD) patients with long disease durations, we assessed cognitive and motor performances, comparing compound heterozygote/homozygote PARKIN carriers to non-carriers Design Cross sectional study Setting Seventeen movement disorders centers Participants Forty-four participants in the Consortium on Risk for Early-Onset PD (CORE-PD) with PD duration greater than median (>14 years), including PARKIN compound heterozygotes/homozygotes combined (n=21), and non-carriers (n=23). Main outcome measures Unified Parkinson’s Disease Rating Scale Part III (UPDRS), Clinical Dementia Rating (CDR) and neuropsychological performance. Linear regression models were applied to assess the association between PARKIN mutation status and cognitive domain scores and UPDRS. Models were adjusted for age, education, disease duration, language, and levodopa equivalent daily dose. Results Compound heterozygote/homozygote PARKIN mutation carriers had earlier AAO of PD (p<0.001) and were younger (p=0.004) at time of examination than non-carriers. They performed better on the MMSE (p=0.010) and were more likely to receive lower scores on the CDR (p=0.003). In multivariate analyses, PARKIN compound heterozygotes/homozygotes performed better on the UPDRS Part III (p=0.017), and on tests of attention (p=0.022), memory (p=0.025) and visuospatial (p=0.024) domains. Conclusions and Relevance Cross-sectional analyses demonstrate better cognitive and motor performance in compound heterozygote/homozygote PARKIN EOPD carriers than non-carriers with long disease duration, suggesting slower disease progression. Longitudinal follow up is required to confirm these findings. PMID:24190026
Beall, Erik B; Lowe, Mark J; Alberts, Jay L; Frankemolle, Anneke M M; Thota, Anil K; Shah, Chintan; Phillips, Michael D
Parkinson's disease (PD) is a progressive neurologic disorder primarily characterized by an altered motor function. Lower extremity forced exercise (FE) has been shown to reduce motor symptoms in patients with PD. Recent functional magnetic resonance imaging (fMRI) studies have shown that FE and medication produce similar changes in brain activation patterns. Functional connectivity MRI (fcMRI) affords the ability to look at how strongly nodes of the motor circuit communicate with each other and can provide insight into the complementary effects of various therapies. Past work has demonstrated an abnormal motor connectivity in patients with PD compared to controls and subsequent normalization after treatment. Here we compare the effects of FE and medication using both resting and continuous visuomotor task fcMRI. Ten patients with mild to moderate PD completed three fMRI and fcMRI scanning sessions randomized under the following conditions: on PD medication, off PD medication, and FE+off medication. Blinded clinical ratings of motor function (a Unified Parkinson's Disease Rating Motor Scale-III exam) indicated that FE and medication resulted in 51% and 33% improvement in clinical ratings, respectively. In most nodes of the motor circuit, the observed changes in the functional connectivity produced by FE and medication were strongly positively correlated. These findings suggest that medication and FE likely use the same pathways to produce symptomatic relief in patients with PD. However, the connectivity changes, while consistent across therapy, were inconsistent in polarity for each patient. This finding may explain some past inconsistencies in connectivity changes after medication therapy.
Lowe, Mark J.; Alberts, Jay L.; Frankemolle, Anneke M.M.; Thota, Anil K.; Shah, Chintan; Phillips, Michael D.
Abstract Parkinson's disease (PD) is a progressive neurologic disorder primarily characterized by an altered motor function. Lower extremity forced exercise (FE) has been shown to reduce motor symptoms in patients with PD. Recent functional magnetic resonance imaging (fMRI) studies have shown that FE and medication produce similar changes in brain activation patterns. Functional connectivity MRI (fcMRI) affords the ability to look at how strongly nodes of the motor circuit communicate with each other and can provide insight into the complementary effects of various therapies. Past work has demonstrated an abnormal motor connectivity in patients with PD compared to controls and subsequent normalization after treatment. Here we compare the effects of FE and medication using both resting and continuous visuomotor task fcMRI. Ten patients with mild to moderate PD completed three fMRI and fcMRI scanning sessions randomized under the following conditions: on PD medication, off PD medication, and FE+off medication. Blinded clinical ratings of motor function (a Unified Parkinson's Disease Rating Motor Scale-III exam) indicated that FE and medication resulted in 51% and 33% improvement in clinical ratings, respectively. In most nodes of the motor circuit, the observed changes in the functional connectivity produced by FE and medication were strongly positively correlated. These findings suggest that medication and FE likely use the same pathways to produce symptomatic relief in patients with PD. However, the connectivity changes, while consistent across therapy, were inconsistent in polarity for each patient. This finding may explain some past inconsistencies in connectivity changes after medication therapy. PMID:23316956
Koenig, Katherine A; Lowe, Mark J; Harrington, Deborah L; Lin, Jian; Durgerian, Sally; Mourany, Lyla; Paulsen, Jane S; Rao, Stephen M
Subtle changes in motor function have been observed in individuals with prodromal Huntington disease (prHD), but the underlying neural mechanisms are not well understood nor is the cumulative effect of the disease (disease burden) on functional connectivity. The present study examined the resting-state functional magnetic resonance imaging (rs-fMRI) connectivity of the primary motor cortex (M1) in 16 gene-negative (NEG) controls and 48 gene-positive prHD participants with various levels of disease burden. The results showed that the strength of the left M1 connectivity with the ipsilateral M1 and somatosensory areas decreased as disease burden increased and correlated with motor symptoms. Weakened M1 connectivity within the motor areas was also associated with abnormalities in long-range connections that evolved with disease burden. In this study, M1 connectivity was decreased with visual centers (bilateral cuneus), but increased with a hub of the default mode network (DMN; posterior cingulate cortex). Changes in connectivity measures were associated with worse performance on measures of cognitive-motor functioning. Short- and long-range functional connectivity disturbances were also associated with volume loss in the basal ganglia, suggesting that weakened M1 connectivity is partly a manifestation of striatal atrophy. Altogether, the results indicate that the prodromal phase of HD is associated with abnormal interhemispheric interactions among motor areas and disturbances in the connectivity of M1 with visual centers and the DMN. These changes may, respectively, contribute to increased motor symptoms, visuomotor integration problems, and deficits in the executive control of movement as individuals approach a manifest diagnosis.
Koenig, Katherine A.; Lowe, Mark J.; Harrington, Deborah L.; Lin, Jian; Durgerian, Sally; Mourany, Lyla; Paulsen, Jane S.
Abstract Subtle changes in motor function have been observed in individuals with prodromal Huntington disease (prHD), but the underlying neural mechanisms are not well understood nor is the cumulative effect of the disease (disease burden) on functional connectivity. The present study examined the resting-state functional magnetic resonance imaging (rs-fMRI) connectivity of the primary motor cortex (M1) in 16 gene-negative (NEG) controls and 48 gene-positive prHD participants with various levels of disease burden. The results showed that the strength of the left M1 connectivity with the ipsilateral M1 and somatosensory areas decreased as disease burden increased and correlated with motor symptoms. Weakened M1 connectivity within the motor areas was also associated with abnormalities in long-range connections that evolved with disease burden. In this study, M1 connectivity was decreased with visual centers (bilateral cuneus), but increased with a hub of the default mode network (DMN; posterior cingulate cortex). Changes in connectivity measures were associated with worse performance on measures of cognitive–motor functioning. Short- and long-range functional connectivity disturbances were also associated with volume loss in the basal ganglia, suggesting that weakened M1 connectivity is partly a manifestation of striatal atrophy. Altogether, the results indicate that the prodromal phase of HD is associated with abnormal interhemispheric interactions among motor areas and disturbances in the connectivity of M1 with visual centers and the DMN. These changes may, respectively, contribute to increased motor symptoms, visuomotor integration problems, and deficits in the executive control of movement as individuals approach a manifest diagnosis. PMID:25072408
Sachse, Michael; Schlitt, Sabine; Hainz, Daniela; Ciaramidaro, Angela; Schirman, Shella; Walter, Henrik; Poustka, Fritz; Bolte, Sven; Freitag, Christine M.
This study broadly examines executive (EF) and visuo-motor function in 30 adolescent and adult individuals with high-functioning autism spectrum disorder (ASD) in comparison to 28 controls matched for age, gender, and IQ. ASD individuals showed impaired spatial working memory, whereas planning, cognitive flexibility, and inhibition were spared.…
Dufrene, Brad A.; Harpole, Lauren Lestremau; Sterling, Heather E.; Perry, Erin J.; Burton, Britney; Zoder-Martell, Kimberly
This study included brief functional analyses and treatment for motor tics exhibited by two children with Tourette Syndrome. Brief functional analyses were conducted in an outpatient treatment center and results were used to develop individualized habit reversal procedures. Treatment data were collected in clinic for one child and in clinic and…
Heinrichs-Graham, Elizabeth; Kurz, Max J; Gehringer, James E; Wilson, Tony W
Shortly after movement termination, there is a strong increase or resynchronization of the beta rhythm (15-30 Hz) across the sensorimotor network of humans, known as the post-movement beta rebound (PMBR). This response has been associated with active inhibition of the motor network following the completion of a movement, sensory afferentation of the sensorimotor cortices, and other functions. However, studies that have directly probed the role of the PMBR in movement execution have reported mixed results, possibly due to differences in the amount of total motor output and/or movement complexity. Herein, we used magnetoencephalography during an isometric-force control task to examine whether alterations in the timing of motor termination demands modulate the PMBR, independent of differences in the motor output itself. Briefly, we manipulated the amount of time between the cue to initiate the force and the cue to terminate the force, such that participants were either forced to terminate quickly or slowly. We also performed a control experiment to test for temporal predictability effects. Our results indicated that the PMBR was stronger immediately following movement termination in the prefrontal cortices, supplementary motor area, left postcentral gyrus, paracentral lobule, and parietal cortex when participants were forced to terminate more quickly. These results were not attributable to the temporal predictability of each condition. These findings support the notion that the PMBR response at least partially serves motor inhibition, independent of the parameters within the motor output itself, and that particular nodes of the motor network may be differentially modulated by motor termination.
Suzuki, Toshiaki; Bunno, Yoshibumi; Onigata, Chieko; Tani, Makiko; Uragami, Sayuri; Yoshida, Sohei
Summary We analyzed thenar muscle F-waves after stimulating the median nerve at the wrist in subjects during two motor imagery conditions: holding and not holding the sensor of a pinch meter between the thumb and index finger. Our aim was to determine whether mental simulation without the muscle contraction associated with motion can increase the excitability of spinal neural function in patients with Parkinson’s disease (PD). F-waves of the left thenar muscles were examined in 10 patients with PD under resting, holding and motor imagery conditions. For the holding condition, the subjects held the sensor of the pinch meter between their thumb and index finger. For the motor imagery conditions, the subjects were asked to imagine a 50% maximal voluntary isometric contraction holding and not holding the sensor of the pinch meter between their thumb and index finger (motor imagery “with”/“without sensor”). Persistence during motor imagery under the “with sensor” condition increased significantly compared with persistence during resting (n=10, z=2.2509, p=0.0244, Wilcoxon test). The F/M amplitude ratio during motor imagery under the “with sensor” condition increased significantly compared with that during resting (n=10, z=2.1915, p=0.0284, Wilcoxon test). Motor imagery under the “with the sensor” condition increased excitability of the spinal neural output to the thenar muscles. Because excitability of the spinal neural output to the thenar muscles during motor imagery “with the sensor” was significantly higher than that during resting, we suggest that movement preparation for a motor imagery task is important in patients with PD. PMID:25764256
Nascimento, Andrey F. Z.; Trindade, Daniel M.; Tonoli, Celisa C. C.; de Giuseppe, Priscila O.; Assis, Leandro H. P.; Honorato, Rodrigo V.; de Oliveira, Paulo S. L.; Mahajan, Pravin; Burgess-Brown, Nicola A.; von Delft, Frank; Larson, Roy E.; Murakami, Mario T.
Myosin V (MyoV) motors have been implicated in the intracellular transport of diverse cargoes including vesicles, organelles, RNA-protein complexes, and regulatory proteins. Here, we have solved the cargo-binding domain (CBD) structures of the three human MyoV paralogs (Va, Vb, and Vc), revealing subtle structural changes that drive functional differentiation and a novel redox mechanism controlling the CBD dimerization process, which is unique for the MyoVc subclass. Moreover, the cargo- and motor-binding sites were structurally assigned, indicating the conservation of residues involved in the recognition of adaptors for peroxisome transport and providing high resolution insights into motor domain inhibition by CBD. These results contribute to understanding the structural requirements for cargo transport, autoinhibition, and regulatory mechanisms in myosin V motors. PMID:24097982
Nascimento, Andrey F Z; Trindade, Daniel M; Tonoli, Celisa C C; de Giuseppe, Priscila O; Assis, Leandro H P; Honorato, Rodrigo V; de Oliveira, Paulo S L; Mahajan, Pravin; Burgess-Brown, Nicola A; von Delft, Frank; Larson, Roy E; Murakami, Mario T
Myosin V (MyoV) motors have been implicated in the intracellular transport of diverse cargoes including vesicles, organelles, RNA-protein complexes, and regulatory proteins. Here, we have solved the cargo-binding domain (CBD) structures of the three human MyoV paralogs (Va, Vb, and Vc), revealing subtle structural changes that drive functional differentiation and a novel redox mechanism controlling the CBD dimerization process, which is unique for the MyoVc subclass. Moreover, the cargo- and motor-binding sites were structurally assigned, indicating the conservation of residues involved in the recognition of adaptors for peroxisome transport and providing high resolution insights into motor domain inhibition by CBD. These results contribute to understanding the structural requirements for cargo transport, autoinhibition, and regulatory mechanisms in myosin V motors.
DNA damage attacks on bacterial cells have been known to activate the SOS response, a transcriptional response affecting chromosome replication, DNA recombination and repair, cell division and prophage induction. All these functions require double-stranded (ds) DNA translocation by ASCE hexameric motors. This review seeks to delineate the structural and functional characteristics of the SOS response and the SOS-regulated DNA translocases FtsK and RuvB with the phi29 bacteriophage packaging motor gp16 ATPase as a prototype to study bacterial motors. While gp16 ATPase, cellular FtsK and RuvB are similarly comprised of hexameric rings encircling dsDNA and functioning as ATP-driven DNA translocases, they utilize different mechanisms to accomplish separate functions, suggesting a convergent evolution of these motors. The gp16 ATPase and FtsK use a novel revolution mechanism, generating a power stroke between subunits through an entropy-DNA affinity switch and pushing dsDNA inward without rotation of DNA and the motor, whereas RuvB seems to employ a rotation mechanism that remains to be further characterized. While FtsK and RuvB perform essential tasks during the SOS response, their roles may be far more significant as SOS response is involved in antibiotic-inducible bacterial vesiculation and biofilm formation as well as the perspective of the bacteria-cancer evolutionary interaction. PMID:24995125
Fernandes, Luciane F. R. M.; Oliveira, Nuno M. L.; Pelet, Danyelle C. S.; Cunha, Agnes F. S.; Grecco, Marco A. S.; Souza, Luciane A. P. S.
BACKGROUND: Distal ulnar nerve injury leads to impairment of hand function due to motor and sensorial changes. Stimulus electrodiagnosis (SE) is a method of assessing and monitoring the development of this type of injury. OBJECTIVE: To identify the most sensitive electrodiagnostic parameters to evaluate ulnar nerve recovery and to correlate these parameters (Rheobase, Chronaxie, and Accommodation) with motor function evaluations. METHOD: A prospective cohort study of ten patients submitted to ulnar neurorrhaphy and evaluated using electrodiagnosis and motor assessment at two moments of neural recovery. A functional evaluation using the DASH questionnaire (Disability of the Arm, Shoulder, and Hand) was conducted at the end to establish the functional status of the upper limb. RESULTS: There was significant reduction only in the Chronaxie values in relation to time of injury and side (with and without lesion), as well as significant correlation of Chronaxie with the motor domain score. CONCLUSION: Chronaxie was the most sensitive SE parameter for detecting differences in neuromuscular responses during the ulnar nerve recovery process and it was the only parameter correlated with the motor assessment. PMID:26786072
Nebel, Mary Beth; Joel, Suresh E; Muschelli, John; Barber, Anita D; Caffo, Brian S; Pekar, James J; Mostofsky, Stewart H
Accumulating evidence suggests that motor impairments are prevalent in autism spectrum disorder (ASD), relate to the social and communicative deficits at the core of the diagnosis and may reflect abnormal connectivity within brain networks underlying motor control and learning. Parcellation of resting-state functional connectivity data using spectral clustering approaches has been shown to be an effective means of visualizing functional organization within the brain but has most commonly been applied to explorations of normal brain function. This article presents a parcellation of a key area of the motor network, the primary motor cortex (M1), a key area of the motor control network, in adults, typically developing (TD) children and children with ASD and introduces methods for selecting the number of parcels, matching parcels across groups and testing group differences. The parcellation is based solely on patterns of connectivity between individual M1 voxels and all voxels outside of M1, and within all groups, a gross dorsomedial to ventrolateral organization emerged within M1 which was left-right symmetric. Although this gross organizational scheme was present in both groups of children, statistically significant group differences in the size and segregation of M1 parcels within regions of the motor homunculus corresponding to the upper and lower limbs were observed. Qualitative comparison of the M1 parcellation for children with ASD with that of younger and older TD children suggests that these organizational differences, with a lack of differentiation between lower limb/trunk regions and upper limb/hand regions, may be due, at least in part, to a delay in functional specialization within the motor cortex.
Toouli, J; Dodds, W J; Honda, R; Sarna, S; Hogan, W J; Komarowski, R A; Linehan, J H; Arndorfer, R C
We studied the opossum sphincter of Oddi (SO) because in this species the SO is approximately 3 cm in length and its extraduodenal location permits recording of motor activity with negligible interference from duodenal motor activity. The SO segment of 120 animals was evaluated by one or more of the following: (a) intraluminal manometry; (b) electromyography; (c) common bile duct (CBD) flow monitored by a drop counter; (d) cineradiography of intraductal contrast medium; and (e) histologic examination. SO pull-throughs using an infused catheter of 0.6-mm o.d. invariably showed a high pressure zone (HPZ) of 18 +/- 3 SE mm Hg in the terminal 4-5 mm of the SO segment. This HPZ had a narrow lumen, 0.5-0.7 mm in diam, and prominent circular muscle. The HPZ in the terminal SO had both active and passive components. HPZ with minimal amplitude and a paucity of underlying smooth muscle were present inconstantly at the junction of the SO segment with the CBD and pancreatic duct, respectively. The dominant feature of the SO segment was rhythmic peristaltic contractions that originated in the proximal SO and propagated toward the duodenum. These contractions occurred spontaneously at a rate of 2-8/min, ranged up to 200 mm Hg in magnitude, had a duration of approximately 5 s and were not abolished by tetrodotoxin. Concurrent myoelectric and manometric recordings showed that each phasic contraction was immediately preceded by an electrical spike burst. Simultaneous recordings of cineradiography, CBD inflow of contrast medium, SO manometry, and SO electromyography indicated that rhythmic peristaltic contractions stripped contrast medium from the SO into the duodenum. During SO systole, CBD emptying was transiently interrupted, whereas SO filling occurred during the diastolic interval between SO peristaltic contractions. SO distention increased the frequency of SO peristalsis. We conclude that (a) the dominant feature of the opossum SO is rhythmic peristaltic contractions that
Logistic regression analyses for predicting clinically important differences in motor capacity, motor performance, and functional independence after constraint-induced therapy in children with cerebral palsy.
Wang, Tien-ni; Wu, Ching-yi; Chen, Chia-ling; Shieh, Jeng-yi; Lu, Lu; Lin, Keh-chung
Given the growing evidence for the effects of constraint-induced therapy (CIT) in children with cerebral palsy (CP), there is a need for investigating the characteristics of potential participants who may benefit most from this intervention. This study aimed to establish predictive models for the effects of pediatric CIT on motor and functional outcomes. Therapists administered CIT to 49 children (aged 3-11 years) with CP. Sessions were 1-3.5h a day, twice a week, for 3-4 weeks. Parents were asked to document the number of restraint hours outside of the therapy sessions. Domains of treatment outcomes included motor capacity (measured by the Peabody Developmental Motor Scales II), motor performance (measured by the Pediatric Motor Activity Log), and functional independence (measured by the Pediatric Functional Independence Measure). Potential predictors included age, affected side, compliance (measured by time of restraint), and the initial level of motor impairment severity. Tests were administered before, immediately after, and 3 months after the intervention. Logistic regression analyses showed that total amount of restraint time was the only significant predictor for improved motor capacity immediately after CIT. Younger children who restrained the less affected arm for a longer time had a greater chance to achieve clinically significant improvements in motor performance. For outcomes of functional independence in daily life, younger age was associated with clinically meaningful improvement in the self-care domain. Baseline motor abilities were significantly predictive of better improvement in mobility and cognition. Significant predictors varied according to the aspects of motor outcomes after 3 months of follow-up. The potential predictors identified in this study allow clinicians to target those children who may benefit most from CIT.
Chow, Ho Ming; Mar, Raymond A; Xu, Yisheng; Liu, Siyuan; Wagage, Suraji; Braun, Allen R
Past experience of everyday life activities, which forms the basis of our knowledge about the world, greatly affects how we understand stories. Yet, little is known about how this influence is instantiated in the human brain. Here, we used functional magnetic resonance imaging to investigate how past experience facilitates functional connectivity during the comprehension of stories rich in perceptual and motor details. We found that comprehenders' past experience with the scenes and actions described in the narratives selectively modulated functional connectivity between lower- and higher-level areas within the neural systems for visual and motor processing, respectively. These intramodal interactions may play an important role in integrating personal knowledge about a narrated situation with an evolving discourse representation. This study provides empirical evidence consistent with the idea that regions related to visual and motor processing are involved in the reenactment of experience as proposed by theories of embodied cognition.
Ogundele, Olalekan Michael; Adeniyi, Philip Adeyemi; Ajonijebu, Duyilemi Chris; Abdulbasit, Amin; Cobham, Ansa Emmanuel; Ishola, Azeez Olakunle; Balogun, Gbolahan Wasiu
Although oxidative stress is characteristic of global vascular occlusion and cyanide toxicity, the pattern of cerebral metabolism reconditioning and rate of progression or reversal of neural tissue damage differ for both forms of ischemia. Thus, it is important to compare cognitive and motor functions in both models of ischemia involving cyanide treatment (CN) and vascular occlusion (VO). Adult Wistar rats (N=30) were divided into three groups; VO (n=12), CN (n=12) and Control-CO (n=6). The CN was treated with 30mg/Kg of potassium cyanide (KCN); VO was subjected to global vascular occlusion-both for duration of 10 days. The control (CO) was fed on normal rat chow and water for the same duration. At day 10, the test and control groups (CN, VO and CO) were subjected to motor function tests (Table edge tests and Open Field Test) and memory function tests (Y-Maze and Novel object recognition) while the withdrawal groups CN-I and VO-I were subjected to the same set of tests at day 20 (the withdrawal phase). The results show that both cyanide toxicity and vascular occlusion caused a decline in motor and memory function when compared with the control. Also, the cyanide treatment produced a more rapid decline in these behavioral parameters when compared with the vascular occlusion during the treatment phase. After the withdrawal phase, cyanide treatment (CN-I) showed either an improvement or restoration of motor and memory function when compared to the CN and control. Withdrawal of vascular occlusion caused no improvement, and in some cases a decline in motor and memory function. In conclusion, cyanide toxicity caused a decline in motor and memory function after the treatment while vascular occlusion caused no significant decline in cognition and motor function at this time. After the withdrawal phase, the effect of cyanide toxicity was reduced and significant improvements were observed in the behavioral tests (motor and cognitive), while a decline in these functions were
Diwadkar, Vaibhav A; Asemi, Avisa; Burgess, Ashley; Chowdury, Asadur; Bressler, Steven L
The dorsal Anterior Cingulate Cortex (dACC) and the Supplementary Motor Area (SMA) are known to interact during motor coordination behavior. We previously discovered that the directional influences underlying this interaction in a visuo-motor coordination task are asymmetric, with the dACC→SMA influence being significantly greater than that in the reverse direction. To assess the specificity of this effect, here we undertook an analysis of the interaction between dACC and SMA in two distinct contexts. In addition to the motor coordination task, we also assessed these effects during a (n-back) working memory task. We applied directed functional connectivity analysis to these two task paradigms, and also to the rest condition of each paradigm, in which rest blocks were interspersed with task blocks. We report here that the previously known asymmetric interaction between dACC and SMA, with dACC→SMA dominating, was significantly larger in the motor coordination task than the memory task. Moreover the asymmetry between dACC and SMA was reversed during the rest condition of the motor coordination task, but not of the working memory task. In sum, the dACC→SMA influence was significantly greater in the motor task than the memory task condition, and the SMA→dACC influence was significantly greater in the motor rest than the memory rest condition. We interpret these results as suggesting that the potentiation of motor sub-networks during the motor rest condition supports the motor control of SMA by dACC during the active motor task condition.
Diwadkar, Vaibhav A.; Asemi, Avisa; Burgess, Ashley; Chowdury, Asadur; Bressler, Steven L.
The dorsal Anterior Cingulate Cortex (dACC) and the Supplementary Motor Area (SMA) are known to interact during motor coordination behavior. We previously discovered that the directional influences underlying this interaction in a visuo-motor coordination task are asymmetric, with the dACC→SMA influence being significantly greater than that in the reverse direction. To assess the specificity of this effect, here we undertook an analysis of the interaction between dACC and SMA in two distinct contexts. In addition to the motor coordination task, we also assessed these effects during a (n-back) working memory task. We applied directed functional connectivity analysis to these two task paradigms, and also to the rest condition of each paradigm, in which rest blocks were interspersed with task blocks. We report here that the previously known asymmetric interaction between dACC and SMA, with dACC→SMA dominating, was significantly larger in the motor coordination task than the memory task. Moreover the asymmetry between dACC and SMA was reversed during the rest condition of the motor coordination task, but not of the working memory task. In sum, the dACC→SMA influence was significantly greater in the motor task than the memory task condition, and the SMA→dACC influence was significantly greater in the motor rest than the memory rest condition. We interpret these results as suggesting that the potentiation of motor sub-networks during the motor rest condition supports the motor control of SMA by dACC during the active motor task condition. PMID:28278267
Champagne, Danielle; Dugas, Claude
The purpose of this case report is to describe the impact of an 11-week hippotherapy program on the gross motor functions of two children (respectively 28 and 37 months old) diagnosed with Down syndrome. Hippotherapy is a strategy that uses the horse's motion to stimulate and enhance muscle contraction and postural control. The children were assessed by the Gross Motor Function Measure (GMFM) and accelerometry. The results indicate that both children improved on many dimensions of the GMFM. Power spectral analysis of the acceleration signals showed improvement in postural control of either the head or trunk, because the children adopted two different adaptative strategies to perturbation induced by the moving horse.
Katić, Ratko; Pejcić, Aleksandra; Viskić-Stalec, Natasa
Four morphological and 7 motor variables were assessed in a sample of 2,235 female children (subdivided into 4 groups) aged 7-11 years, elementary school first- to fourth-graders from the Primorje-Gorski Kotar County, Republic of Croatia. The study objective was to analyze the morphological-motor structures according to age. Factor analysis was done for each of the four subject groups. Results clearly showed the morphological-motor functioning of the girls to change with age. Developmental processes lead to the formation of a general morphological factor defined as ectomesomorph and two general mechanisms responsible for motor efficiency in the form of strength regulation and speed regulation. The results obtained were found to be consistent with the existing relevant models related to the morphological, motor, functional and cognitive systems. The more so, these results allow for a supramodel to design, which will integrate relevant elements of all these models to define the function of the body as a whole.
Vukovic, Nikola; Feurra, Matteo; Shpektor, Anna; Myachykov, Andriy; Shtyrov, Yury
Among various questions pertinent to grounding human cognitive functions in a neurobiological substrate, the association between language and motor brain structures is a particularly debated one in neuroscience and psychology. While many studies support a broadly distributed model of language and semantics grounded, among other things, in the general modality-specific systems, theories disagree as to whether motor and sensory cortex activity observed during language processing is functional or epiphenomenal. Here, we assessed the role of motor areas in linguistic processing by investigating the responses of 28 healthy volunteers to different word types in semantic and lexical decision tasks, following repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex. We found that early rTMS (delivered within 200ms of word onset) produces a left-lateralised and meaning-specific change in reaction speed, slowing down behavioural responses to action-related words, and facilitating abstract words - an effect present only during semantic, but not lexical, decision. We interpret these data in light of action-perception theory of language, bolstering the claim that motor cortical areas play a functional role in language comprehension.
Rasouli, Omid; Fors, Egil A; Borchgrevink, Petter Chr; Öhberg, Fredrik; Stensdotter, Ann-Katrin
Purpose This paper aimed to investigate motor proficiency in fine and gross motor function, with a focus on reaction time (RT) and movement skill, in patients with fibromyalgia (FM) and chronic fatigue syndrome (CFS) compared to healthy controls (HC). Methods A total of 60 individuals (20 CFS, 20 FM, and 20 HC), age 19–49 years, participated in this study. Gross motor function in the lower extremity was assessed using a RT task during gait initiation in response to an auditory trigger. Fine motor function in the upper extremity was measured during a precision task (the Purdue Pegboard test) where the number of pins inserted within 30 s was counted. Results No significant differences were found between FM and CFS in any parameters. FM and CFS groups had significantly longer RT than HC in the gait initiation (p=0.001, and p=0.004 respectively). In the Purdue Pegboard test, 20% in the FM group, 15% in the CFS groups, and 0% of HC group, scored below the threshold of the accepted performance. However, there were no significant differences between FM, CFS, and HC in this task (p=0.12). Conclusion Compared to controls, both CFS and FM groups displayed significantly longer RT in the gait initiation task. Generally, FM patients showed the worst results in both tests, although no group differences were found in fine motor control, according to the Purdue Pegboard test. PMID:28223840
Rengaraj, Deivendran; Kwon, Woo-Sung; Pang, Myung-Geol
Air pollution is consistently associated with various diseases and subsequent death among children, adult, and elderly people worldwide. Motor vehicle exhaust contributes to a large proportion of the air pollution present. The motor vehicle exhaust systems emit a variety of toxic components, including carbon monoxide, nitrogen oxides, volatile organic compounds, ozone, particulate matter, and polycyclic aromatic hydrocarbons. Several epidemiological studies and laboratory studies have demonstrated that these components are potentially mutagenic, carcinogenic, and endocrine disrupting agents. However, their impact on male reproductive function and associated proteins is not very clear. Therefore, a comprehensive review on the effects of motor vehicle exhaust on male reproductive function and associated proteins is needed to better understand the risks of exhaust exposure for men. We found that motor vehicle exhaust can cause harmful effects on male reproductive functions by altering organ weights, reducing the spermatozoa qualities, and inducing oxidative stress. Remarkably, motor vehicle exhaust exposure causes significant changes in the expression patterns of proteins that are key components involved in spermatogenesis and testosterone synthesis. In conclusion, this review helps to describe the risks of vehicle exhaust exposure and its relationship to potential adverse effects on the male reproduction system.
Coco, Marinella; Perciavalle, Vincenzo
Until the end of 18th century, the role of the cerebellum remained obscure. The turning point occurred when Luigi Galvani showed that muscle contraction is due to electricity and Alessandro Volta produced the battery, an apparatus based on the pairing of silver and zinc plates separated by brine soaked paper disks, capable to generate electricity. Luigi Rolando, at beginning of 19th century, was impressed by these two observations. He thought that, since the brain generates the movement, it must contain a device generating electricity. As a battery, it should be formed by overlapping disks and the cerebellum for Rolando seemed to be the right structure for such a characteristic laminar organization. He argued that, if the cerebellum is the battery that produces electricity for muscle activity, its removal would produce paralysis. Consequently, Rolando removed the cerebellum in a young goat and observed that the animal, before dying, could no longer stand up. He concluded that the cerebellum is a motor structure as it generates the electricity which produces the movement. The conclusions of Rolando were criticized by Marie-Jean-Pierre Flourens who observed that animals undergoing cerebellectomy were still able to move, even if with problems of balance. Flourens concluded that the role of the cerebellum "is to put in order or to coordinate movements wanted by certain parts of the nervous system, excited by others". It was necessary to wait up to 1891 when Luigi Luciani, observing a dog survived the cerebellectomy, described a triad of symptoms (asthenia, atony and astasis), unquestionably of cerebellar origin.
Nasiri, Jafar; Safavifar, Faezeh
Gross motor dysfunction is considered as the most challenging problem in cerebral palsy (CP). It is proven that improvement of gross motor function could reduce CP-related disabilities and provide better quality of life in this group of patients. Therefore, the aim of this trial is to evaluate the effectiveness of cerebrolysin (CBL) on gross motor function of children with CP who are undergoing treatment. In this clinical trial study, paediatric patients aged 18-75 months with spastic diplegic or quadriplegic cerebral palsy, who were under rehabilitation therapy, were selected and randomly allocated in control and CBL groups. Patients in CBL group underwent treatment with standard rehabilitation therapy plus CBL. The latter was administrated intramuscularly as a single daily dose of 0.1 cc/kg for 10 days and then continued weekly for 4 months. Gross motor function of participants in the two studied groups, before and after trial, was evaluated and compared using the validated Persian version of gross motor function classification system-expanded and revised (GMFCS-E&R). During this trial, 108 patients with CP were evaluated for eligibility. From these, 50 patients were enrolled and randomly allocated in the CBL and control groups. Four months after trial, the mean level of GMFCS decreased significantly in the two groups (P < 0.05). However, it was significantly lower in the CBL group than in the control group (2.1 vs. 3.16, P < 0.05). The results of this trial indicated that CBL could improve gross motor function in patients with CP. This finding is consistent with neurotrophic and neuroprotective effects of CBL, which have been reported in various clinical trials in other neurological disorders. Further studies are recommended to establish the value of continued neuroprotection and to determine the pharmacokinetics/dynamics of CBL in this group of patients.
Jones, R D; Donaldson, I M; Parkin, P J
After unilateral cerebral hemisphere stroke, resulting in contralateral arm symptoms but largely sparing higher cerebral function, ipsilateral arm function is generally considered to be unaffected. In this study, 8 subjects with acute unilateral cerebral infarction (confirmed by CT scan) and primarily motor deficits underwent 11 computerized and 6 clinical assessments between 11 days and 12 months poststroke, and were compared with 12 normal subjects. Computerized tests comprised 3 pursuit tracking tasks (preview-random, step and a combination of these), designed to measure different aspects of integrated sensory-motor (S-M) function, and 12 tasks aimed at breaking tracking into various sensory, perceptual and motor components (joint movement sense, visual resolution, object perception, static and dynamic visuospatial perception, range of movement, grip and arm strength, reaction time, speed, static and dynamic steadiness). The asymptomatic arm was impaired on all but one of the computerized tests throughout the 12-month period, although to a lesser degree than the symptomatic arm. Grip strength was marginally impaired initially. Incomplete neurological recovery was seen in the asymptomatic arm for all functions except strength, speed and steadiness, possibly indicating their resistance to improvement. Clinical assessment detected no asymptomatic arm impairment and only a mild transient deficit of higher mental function. Our data suggest that (1) all cerebral hemisphere areas involved in S-M functions can exert some degree of bilateral motor control; (2) ipsilateral influence is never greater than contralateral influence, and is usually considerably less; and (3) the proportion of ipsilateral to contralateral control is closely related to the degree of continuous sensory feedback required by the particular task. The mechanism and degree of ipsilateral dysfunction can be explained by a 3-tier cerebral model of S-M integration comprising a lower level of functions
Frank, Cornelia; Land, William M.; Popp, Carmen; Schack, Thomas
Recent research on mental representation of complex action has revealed distinct differences in the structure of representational frameworks between experts and novices. More recently, research on the development of mental representation structure has elicited functional changes in novices' representations as a result of practice. However, research investigating if and how mental practice adds to this adaptation process is lacking. In the present study, we examined the influence of mental practice (i.e., motor imagery rehearsal) on both putting performance and the development of one's representation of the golf putt during early skill acquisition. Novice golfers (N = 52) practiced the task of golf putting under one of four different practice conditions: mental, physical, mental-physical combined, and no practice. Participants were tested prior to and after a practice phase, as well as after a three day retention interval. Mental representation structures of the putt were measured, using the structural dimensional analysis of mental representation. This method provides psychometric data on the distances and groupings of basic action concepts in long-term memory. Additionally, putting accuracy and putting consistency were measured using two-dimensional error scores of each putt. Findings revealed significant performance improvements over the course of practice together with functional adaptations in mental representation structure. Interestingly, after three days of practice, the mental representations of participants who incorporated mental practice into their practice regime displayed representation structures that were more similar to a functional structure than did participants who did not incorporate mental practice. The findings of the present study suggest that mental practice promotes the cognitive adaptation process during motor learning, leading to more elaborate representations than physical practice only. PMID:24743576
Ishida, Akimasa; Tamakoshi, Keigo; Hamakawa, Michiru; Shimada, Haruka; Nakashima, Hiroki; Masuda, Tadashi; Hida, Hideki; Ishida, Kazuto
Intensive use of the impaired forelimb promotes behavioral recovery and induces plastic changes of the central nervous system after stroke. However, the optimal onset of intensive use treatment after stroke is controversial. In this study, we investigated whether early forced impaired limb use (FLU) initiated 24h after intracerebral hemorrhage (ICH) of the internal capsule affected behavioral recovery and histological damage. Rats were subjected to ICH via low-dose collagenase infusion or sham stroke. One day after surgery, the ipsilateral forelimbs of half of the ICH and sham rats were casted for a week to induce the use of their contralateral forelimbs. Behavioral assessments were performed on days 10-12 and 26-28 after the surgery and followed by histological assessments. Improvements in skilled reaching and coordinated stepping function were found in the FLU-treated group in comparison with the untreated group after ICH. Additionally, FLU-treated ICH animals showed more normal and precise reaching and stepping movements as compared with ICH control animals. In contrast, FLU did not have a significant impact on gross sensory-motor functions such as the motor deficit score, contact placing response and spontaneous usage of the impaired paw. The volume of tissue lost and the number of spared corticospinal neurons in lesioned motor cortex were not affected by early FLU after ICH. These findings demonstrate the efficacy of early focused use of an impaired limb after internal capsule hemorrhage.
Menon, Samir; Brantner, Gerald; Aholt, Chris; Kay, Kendrick; Khatib, Oussama
A challenging problem in motor control neuroimaging studies is the inability to perform complex human motor tasks given the Magnetic Resonance Imaging (MRI) scanner's disruptive magnetic fields and confined workspace. In this paper, we propose a novel experimental platform that combines Functional MRI (fMRI) neuroimaging, haptic virtual simulation environments, and an fMRI-compatible haptic device for real-time haptic interaction across the scanner workspace (above torso ∼ .65×.40×.20m(3)). We implement this Haptic fMRI platform with a novel haptic device, the Haptic fMRI Interface (HFI), and demonstrate its suitability for motor neuroimaging studies. HFI has three degrees-of-freedom (DOF), uses electromagnetic motors to enable high-fidelity haptic rendering (>350Hz), integrates radio frequency (RF) shields to prevent electromagnetic interference with fMRI (temporal SNR >100), and is kinematically designed to minimize currents induced by the MRI scanner's magnetic field during motor displacement (<2cm). HFI possesses uniform inertial and force transmission properties across the workspace, and has low friction (.05-.30N). HFI's RF noise levels, in addition, are within a 3 Tesla fMRI scanner's baseline noise variation (∼.85±.1%). Finally, HFI is haptically transparent and does not interfere with human motor tasks (tested for .4m reaches). By allowing fMRI experiments involving complex three-dimensional manipulation with haptic interaction, Haptic fMRI enables-for the first time-non-invasive neuroscience experiments involving interactive motor tasks, object manipulation, tactile perception, and visuo-motor integration.
Wang, Hui-Yi; Huang, Tzu-Hsiu; Lo, Sing-Kai
Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder. Previous studies have reported that children with ADHD exhibit deficits of adaptive function and insufficient motor ability. The objective of this study was to investigate the association between adaptive function and motor ability in children with ADHD compared with a group of normal children. The study group included 25 children with ADHD (19 boys and 6 girls), aged from 4.6 years to 8.6 years (mean±standard deviation, 6.5±1.2). A group of 24 children without ADHD (normal children) were selected to match the children with ADHD on age and gender. The Movement Assessment Battery for Children, which includes three subtests, was used to assess the motor ability of the children of both groups. The Chinese version of Adaptive Behavior Scales, which consists of 12 life domains, was used to assess adaptive function of the children with ADHD. Compared with the normal children, children with ADHD exhibited poorer motor ability on all the three subtests of motor assessment. In the ADHD group, nine (36%) children had significant motor impairments and seven (28%) were borderline cases. A total of 10 (40%) children with ADHD had definite adaptive problems in one or more adaptive domains. With statistically controlling of IQ for the ADHD group, those children with impaired motor ability had significantly poorer behaviors in the adaptive domain of home living (p=0.035). Moreover, children with ADHD who had severely impaired manual dexterity performed worse than the control group in the adaptive domains of home living (r=-0.47, p=0.018), socialization (r=-0.49, p=0.013), and self-direction (r=-0.41, p=0.040). In addition, children with poorer ball skills had worse home living behavior (r=-0.56, p=0.003). Children who had more impaired balance exhibited poorer performance in social behavior (r=-0.41, p=0.040). This study found significant correlation between motor ability and adaptive
Williamson, Sally M; Willis, Sarah J; Wright, Geraldine A
Systemic pesticides such as neonicotinoids are commonly used on flowering crops visited by pollinators, and their use has been implicated in the decline of insect pollinator populations in Europe and North America. Several studies show that neonicotinoids affect navigation and learning in bees but few studies have examined whether these substances influence their basic motor function. Here, we investigated how prolonged exposure to sublethal doses of four neonicotinoid pesticides (imidacloprid, thiamethoxam, clothianidin, dinotefuran) and the plant toxin, nicotine, affect basic motor function and postural control in foraging-age worker honeybees. We used doses of 10 nM for each neonicotinoid: field-relevant doses that we determined to be sublethal and willingly consumed by bees. The neonicotinoids were placed in food solutions given to bees for 24 h. After the exposure period, bees were more likely to lose postural control during the motor function assay and fail to right themselves if exposed to imidacloprid, thiamethoxam, clothianidin. Bees exposed to thiamethoxam and nicotine also spent more time grooming. Other behaviours (walking, sitting and flying) were not significantly affected. Expression of changes in motor function after exposure to imidacloprid was dose-dependent and affected all measured behaviours. Our data illustrate that 24 h exposure to sublethal doses of neonicotinoid pesticides has a subtle influence on bee behaviour that is likely to affect normal function in a field setting.
Miwa, Hiroto; Kondo, Takashi; Oshima, Tadayuki; Fukui, Hirokazu; Tomita, Toshihiko; Watari, Jiro
Noxious stimuli in the esophagus activate nociceptive receptors on esophageal mucosa, such as transient receptor potential, acid-sensing ion channel and the P2X family, a family of ligand-gated ion channels responsive to ATP, and this generates signals that are transmitted to the central nervous system via either spinal nerves or vagal nerves, resulting in esophageal sensation. Among the noxious stimuli, gastric acid and other gastric contents are clinically most important, causing typical reflux symptoms such as heartburn and regurgitation. A conventional acid penetration theory has been used to explain the mechanism of heartburn, but much recent evidence does not support this theory. Therefore, it may be necessary to approach the causes of heartburn symptoms from a new conceptual framework. Hypersensitivity of the esophagus, like that of other visceral organs, includes peripheral, central and probably psychosocial factor-mediated hypersensitivity, and is known to play crucial roles in the pathoegenesis of nonerosive reflux disease, functional heartburn and non-cardiac chest pain. There also are esophagitis patients who do not perceive typical symptoms. This condition is known as silent gastroesophageal reflux disease. Although the pathogenesis of silent gastroesophageal reflux disease is still not known, hyposensitivity to reflux of acid may possibly explain the condition.
Bernard-Marissal, Nathalie; Médard, Jean-Jacques; Azzedine, Hamid; Chrast, Roman
Mutations in Sigma 1 receptor (SIGMAR1) have been previously identified in patients with amyotrophic lateral sclerosis and disruption of Sigmar1 in mouse leads to locomotor deficits. However, cellular mechanisms underlying motor phenotypes in human and mouse with disturbed SIGMAR1 function have not been described so far. Here we used a combination of in vivo and in vitro approaches to investigate the role of SIGMAR1 in motor neuron biology. Characterization of Sigmar1(-/-) mice revealed that affected animals display locomotor deficits associated with muscle weakness, axonal degeneration and motor neuron loss. Using primary motor neuron cultures, we observed that pharmacological or genetic inactivation of SIGMAR1 led to motor neuron axonal degeneration followed by cell death. Disruption of SIGMAR1 function in motor neurons disturbed endoplasmic reticulum-mitochondria contacts, affected intracellular calcium signalling and was accompanied by activation of endoplasmic reticulum stress and defects in mitochondrial dynamics and transport. These defects were not observed in cultured sensory neurons, highlighting the exacerbated sensitivity of motor neurons to SIGMAR1 function. Interestingly, the inhibition of mitochondrial fission was sufficient to induce mitochondria axonal transport defects as well as axonal degeneration similar to the changes observed after SIGMAR1 inactivation or loss. Intracellular calcium scavenging and endoplasmic reticulum stress inhibition were able to restore mitochondrial function and consequently prevent motor neuron degeneration. These results uncover the cellular mechanisms underlying motor neuron degeneration mediated by loss of SIGMAR1 function and provide therapeutically relevant insight into motor neuronal diseases.
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.
Guojun, Zhang; Duanyu, Ni; Fu, Paul; Lixin, Cai; Tao, Yu; Wei, Du; Liang, Qiao; Zhiwei, Ren
This study aimed to investigate the threshold of cortical electrical stimulation (CES) for functional brain mapping during surgery for the treatment of rolandic epilepsy. A total of 21 patients with rolandic epilepsy who underwent surgical treatment at the Beijing Institute of Functional Neurosurgery between October 2006 and March 2008 were included in this study. Their clinical data were retrospectively collected and analyzed. The thresholds of CES for motor response, sensory response, and after discharge production along with other threshold-related factors were investigated. The thresholds (mean ± standard deviation) for motor response, sensory response, and after discharge production were 3.48 ± 0.87, 3.86 ± 1.31, and 4.84 ± 1.38 mA, respectively. The threshold for after discharge production was significantly higher than those of both the motor and sensory response (both p<0.05). A negative linear correlation was found between the threshold of after discharge production and disease duration. Using the CES parameters at a stimulation frequency of 50 Hz and a pulse width of 0.2 ms, the threshold of sensory and motor responses were similar, and the threshold of after discharge production was higher than that of sensory and motor response.
Severe cervical Spinal Cord Injury (SCI) leads to quadriplegia, and autonomic dysfunctions. Bladder/bowel continence, cardiovascular performance, and breathing are impaired besides movements. Even though there are no fully restorative treatments for SCI, I report about a patient, who suffered a severe cervical, motoric complete SCI, in whom urinary bladder functions were fully repaired by functional and structural repair (limited regeneration of the cord) upon 2.5 years of Coordination Dynamics Therapy (CDT). On the repair of the blood circulation (no occurrence of pressure ulcers any more), breathing and motor functions was reported earlier. The mechanism that underlies this important repair of urinary bladder functions is the learning transfer from movements to bladder functions. The human bladder repair is analyzed at the neuron level, the collective variable level (System Theory of Pattern Formation), the movement, and the clinical diagnostic level.
Winship, Daniel H.; Zboralske, F. Frank
The response of the normal human esophagus to an obstructing intraluminal bolus was investigated and compared to the response evoked by transient intraluminal distention. A balloon, immobilized within the esophagus by external attachment to a force transducer, was inflated with from 3 to 25 ml of air for from 3 to 210 sec. Pressure phenomena occurring in the esophagus were simultaneously recorded from the body of the esophagus above and below the balloon. Transient distention (5 sec or less) with small volumes (5 ml or less) often evoked a secondary peristaltic wave in the esophagus distal to the balloon, but infrequently resulted in the registration of any force exerted upon the balloon to drive it downward. Conversely, distentions of longer duration and with greater volume elicited an esophageal propulsive force exerted upon the balloon oriented to propel it aborally, and much less often evoked a propagated wave of secondary peristalsis. The propulsive force, obviously resulting from esophageal muscular contraction, occurred promptly, and once initiated, was sustained until deflation of the balloon. It varied widely in magnitude, from 4 to 200 g, and was associated with no motor phenomena recorded from the body of the esophagus proximal or distal to the balloon which could account for its presence, onset, magnitude, or duration. The force was inhibited by deglutition, but arrival of the primary peristaltic wave at the bolus resulted in augmentation of the force. When the obstructing balloon was freed from its attachment, the persistent, stationary force was converted to a propagated one that propelled the balloon before it. It the balloon was arrested before entering the stomach, the moving contraction was also arrested and the persistent propulsive force acting upon the balloon was maintained. The velocity of the moving contraction wave was determined in great part by the resistance offered by the bolus. Unrestrained, the balloon was propelled aborally at 4-8 cm
BACKGROUND: Many foods rich in antioxidant and anti-inflammatory compounds have been shown to increase health and reduce markers of aging. A number of berry fruits high in polyphenols are known to ameliorate age-related declines in cellular, cognitive and behavioral function in rats. OBJECTIVES: Thi...
Adenocarcinoma of the Gastroesophageal Junction; Esophageal Adenocarcinoma; Stage IB Esophageal Cancer; Stage IIA Esophageal Cancer; Stage IIB Esophageal Cancer; Stage IIIA Esophageal Cancer; Stage IIIB Esophageal Cancer
MacDonald, Megan; Lipscomb, Shannon; McClelland, Megan M.; Duncan, Rob; Becker, Derek; Anderson, Kim; Kile, Molly
Purpose: The purpose of this article was to examine specific linkages between early visual-motor integration skills and executive function, as well as between early object manipulation skills and social behaviors in the classroom during the preschool year. Method: Ninety-two children aged 3 to 5 years old (M[subscript age] = 4.31 years) were…
Asai, Tomohisa; Sugimori, Eriko; Tanno, Yoshihiko
Atypical cerebral lateralization in motor and language functions in regard to schizotypal personality traits in healthy populations, as well as among schizophrenic patients, has attracted attention because these traits may represent a risk factor for schizophrenia. Although the relationship between handedness and schizotypal personality has been…
LeMonda, Brittany C.; Holtzer, Roee; Goldman, Sylvie
This study reports on the relationship between motor stereotypies and impairments in executive functions (EF) in children with Autistic Disorder (AD) and in children with Developmental Language Disorders (DLD). We hypothesized that low EF performance would predict higher frequency and longer durations of stereotypies in the AD group only.…
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...
Sohn, William Seunghyun; Yoo, Kwangsun; Jeong, Yong
Recent studies have shown that blood oxygen level-dependent low-frequency (<0.1 Hz) fluctuations (LFFs) during a resting-state exhibit a high degree of correlation with other regions that share cognitive function. Initial studies of resting-state network mapping have focused primarily on major networks such as the default mode network, primary motor, somatosensory, visual, and auditory networks. However, more specific or subnetworks, including those associated with specific motor functions, have yet to be properly addressed. We performed independent component analysis (ICA) in a specific target region of the brain, a process we name, "localized ICA." We demonstrated that when ICA is applied to localized fMRI data, it can be used to distinguish resting-state LFFs associated with specific motor functions (e.g., finger tapping, foot movement, or bilateral lip pulsing) in the primary motor cortex. These ICA components generated from localized data can then be used as functional regions of interest to map whole-brain connectivity. In addition, this method can be used to visualize inter-regional connectivity by expanding the localized region and identifying components that show connectivity between the two regions.
Rosenbaum, Peter L.; Palisano, Robert J.; Bartlett, Doreen J.; Galuppi, Barbara E.; Russell, Dianne J.
The Gross Motor Function Classification System (GMFCS) for cerebral palsy has been widely used internationally for clinical, research, and administrative purposes. This paper recounts the ideas and work behind the creation of the GMFCS, reports on the lessons learned, and identifies some philosophical challenges inherent in trying to develop an…
Cid, Maria R.
The purpose of this research was to investigate if motor skills could be used as a differentiating feature between Asperger's Disorder (AD) and High Functioning (HFA) in children under the age of 9 years, 0 months, in order to provide additional information regarding the usefulness and validity of distinguishing these two disorders. There is…
Wunsch, Kathrin; Pfister, Roland; Henning, Anne; Aschersleben, Gisa; Weigelt, Matthias
The present study examined the developmental trajectories of motor planning and executive functioning in children. To this end, we tested 217 participants with three motor tasks, measuring anticipatory planning abilities (i.e., the bar-transport-task, the sword-rotation-task and the grasp-height-task), and three cognitive tasks, measuring executive functions (i.e., the Tower-of-Hanoi-task, the Mosaic-task, and the D2-attention-endurance-task). Children were aged between 3 and 10 years and were separated into age groups by 1-year bins, resulting in a total of eight groups of children and an additional group of adults. Results suggested (1) a positive developmental trajectory for each of the sub-tests, with better task performance as children get older; (2) that the performance in the separate tasks was not correlated across participants in the different age groups; and (3) that there was no relationship between performance in the motor tasks and in the cognitive tasks used in the present study when controlling for age. These results suggest that both, motor planning and executive functions are rather heterogeneous domains of cognitive functioning with fewer interdependencies than often suggested. PMID:27462285
Imms, Christine; Carlin, John; Eliasson, Ann-Christin
Aim: To examine the stability of caregiver-reported classifications of function of children with cerebral palsy (CP) measured 12 months apart. Method: Participants were 86 children (50 males, 36 females) with CP of all motor types and severities who were recruited into a population-based longitudinal study. Children were aged 11 years 8 months (SD…
Jadcherla, Sudarshan R; Parks, Vanessa N; Peng, Juan; Dzodzomenyo, Samuel; Fernandez, Soledad; Shaker, Reza; Splaingard, Mark
Electrocortical arousal (ECA) as an effect of visceral provocation or of its temporal relationships with aerodigestive reflexes in premature neonates is not known. We tested the hypothesis that esophageal provocation results in both esophageal reflex responses and ECAs during sleep and that ECAs are dependent on the frequency characteristics of esophageal neuromotor responses. We defined the spatiotemporal relationship of ECAs in relation to 1) spontaneous pharyngoesophageal swallow sequences and gastroesophageal reflux (GER) events and 2) sensory-motor characteristics of esophageal reflexes. Sixteen healthy premature neonates born at 27.9 ± 3.4 wk were tested at 36.8 ± 1.9 wk postmenstrual age. Ninety-five midesophageal and 31 sham stimuli were given in sleep during concurrent manometry and videopolysomnography. With stimulus onset as reference point, we scored the response latency, frequency occurrence and duration of arousals, peristaltic reflex, and upper esophageal sphincter contractile reflex (UESCR). Changes in polysomnography-respiratory patterns and esophageal sensory-motor parameters were scored by blinded observers. Significantly (for each characteristic listed, P < 0.05), swallow sequences were associated with arousals and sleep state changes, and arousals were associated with incomplete peristalsis, response delays to lower esophageal sphincter relaxation, and prolonged esophageal clearance. GER events (73.5%) provoked arousals, and arousals were associated with response delays to peristaltic reflexes or clearance, sleep state modification, and prolonged respiratory arousal. Midesophageal stimuli (54%) provoked arousals and were associated with increased frequency, prolonged latency, prolonged response duration of peristaltic reflexes and UESCR, and increased frequency of sleep state changes and respiratory arousals. In human neonates, ECAs are provoked upon esophageal stimulation; the sensory-motor characteristics of esophageal reflexes are distinct
Ximenes, Manoel; Piauilino, Marcos Amorim; Oliveira, Humberto Alves; Vaz Neto, Jorge Pinto
We describe the case of a 54 year old woman seen with an esophageal mass diagnosed as a primary esophageal lymphoma. The main symptom was dysphagia of seven months duration. The treatment consisted in resection of the tumor, and reconstruction of the defect with a reversed pleural flap, followed by a chemotherapy regimen that consisted of five drugs, cyclophosphamid, prednisone, doxorubicin, rituximab and vincristine (R-CHOP). The patient developed an esophageal pleural fistula treated with pleural drainage and irrigation that closed in 45 days. Two and one half years later she is doing well and disease free.
Zhang, W; Chen, J; Zhai, T; Yan, L; Chen, C
Purpose: To explore the effect of the Jaw-tracking with RapidArc(JT-RapidArc) plans for upper thoracic esophageal cancer. Methods: Treatment planning was designed by using RapidArc and JT-RapidArc techniques for 11 consecutive patients. The dose-volume histogram parameters of PTV and the organs at risk(OAR), conformity index(CI), heterogeneity index(HI), low dose volume of normal tissue(B-P) and monitor units(MUs) were compared between the different techniques. Results: JT-RapidArc plans provided the better coverage of PTV1(64) D98 and HI(P<0.05), lower MLD, D2 of PTV1(64) and PTV2(54), but no statistically difference in CI(P>0.05), which comparison with RapidArc plans. Plans with JT- RapidArc had lower Lung of V5, V10, V13, V20, V30, MLD(P<0.05); heart of V20, MLD(P<0.05); and B-P of V5, V10, V15, V20, V30(P<0.05); but no significantly different in Spinal cord and SC-PRV as compared with RapidArc plans. JT-RapidArc plans increaseed the MUs by 1%(P>0.05) as compared with RapidArc plans. Conclusion: All of the plans had met the requirements of clinical dosimetry. JT-RapidArc plans as compared with RapidArc plans, showing better part of target coverage, part of OARS(lung and heart) and heart and B-P sparing, which MUs was slightly increased. This work was sponsored by Shantou University Medical College Clinical Research Enhancement Initiative(NO.201424)
Jones, Paul W.; Borich, Michael R.; Vavsour, Irene; Mackay, Alex; Boyd, Lara A.
Introduction Hemiparesis is one of the most prevalent chronic disabilities after stroke. Biochemical and structural magnetic resonance imaging approaches may be employed to study the neural substrates underpinning upper-extremity (UE) recovery after chronic stroke. Objective The purposes of this study were to 1) quantify anatomical and metabolic differences in the precentral gyrus, and 2) test the relationships between anatomical and metabolic differences, and hemiparetic arm function in individuals in the chronic stage of stroke recovery. Our hypotheses were: 1) the Stroke group would exhibit reduced precentral gyrus cortical thickness and lower concentrations of total N-acetylaspartate (tNAA) and glutamate+glutamine (Glx) in the ipsilesional motor cortex; and 2) that each of these measures would be associated with UE motor function after stroke. Methods Seventeen individuals with chronic (>6 months) subcortical ischemic stroke and eleven neurologically healthy controls were recruited. Single voxel proton magnetic resonance spectroscopy (H1MRS) was performed to measure metabolite concentrations of tNAA and Glx in the precentral gyrus in both ipsilesional and contralesional hemispheres. Surface-based cortical morphometry was used to quantify precentral gyral thickness. Upper-extremity motor function was assessed using the Wolf Motor Function Test (WMFT). Results Results demonstrated significantly lower ipsilesional tNAA and Glx concentrations and precentral gyrus thickness in the Stroke group. Ipsilesional tNAA and Glx concentration and precentral gyrus thickness was significantly lower in the ipsilesional hemisphere in the Stroke group. Parametric correlation analyses revealed a significant positive relationship between precentral gyrus thickness and tNAA concentration bilaterally. Multivariate regression analyses revealed that ipsilesional concentrations of tNAA and Glx predicted the largest amount of variance in WMFT scores. Cortical thickness measures alone did
Dinomais, Mickael; Hertz-Pannier, Lucie; Groeschel, Samuel; Chabrier, Stéphane; Delion, Matthieu; Husson, Béatrice; Kossorotoff, Manoelle; Renaud, Cyrille; Nguyen The Tich, Sylvie
Motor outcome is variable following neonatal arterial ischemic stroke (NAIS). We analyzed the relationship between lesion characteristics on brain MRI and motor function in children who had suffered from NAIS. Thirty eight full term born children with unilateral NAIS were investigated at the age of seven. 3D T1- and 3D FLAIR-weighted MR images were acquired on a 3T MRI scanner. Lesion characteristics were compared between patients with and without cerebral palsy (CP) using the following approaches: lesion localization either using a category-based analysis, lesion mapping as well as voxel-based lesion-symptom mapping (VLSM). Using diffusion-weighted imaging the microstructure of the cortico-spinal tract (CST) was related to the status of CP by measuring DTI parameters. Whereas children with lesions sparing the primary motor system did not develop CP, CP was always present when extensive lesions damaged at least two brain structures involving the motor system. The VLSM approach provided a statistical map that confirmed the cortical lesions in the primary motor system and revealed that CP was highly correlated with lesions in close proximity to the CST. In children with CP, diffusion parameters indicated microstructural changes in the CST at the level of internal capsule and the centrum semiovale. White matter damage of the CST in centrum semiovale was a highly reproducible marker of CP. This is the first description of the implication of this latter region in motor impairment after NAIS. In conclusion, CP in childhood was closely linked to the location of the infarct in the motor system.
Wuang, Y.-P.; Wang, C.-C.; Huang, M.-H.; Su, C.-Y.
Background: The purpose of the study was to describe sensorimotor profile in children with mild intellectual disability (ID), and to examine the association between cognitive and motor function. Methods: A total of 233 children with mild ID aged 7 to 8 years were evaluated with measures of cognitive, motor and sensory integrative functioning.…
Maliga, Zoltan; Junqueira, Magno; Toyoda, Yusuke; Ettinger, Andreas; Mora-Bermúdez, Felipe; Klemm, Robin W; Vasilj, Andrej; Guhr, Elaine; Ibarlucea-Benitez, Itziar; Poser, Ina; Bonifacio, Ezio; Huttner, Wieland B; Shevchenko, Andrej; Hyman, Anthony A
Coordination of multiple kinesin and myosin motors is required for intracellular transport, cell motility and mitosis. However, comprehensive resources that allow systems analysis of the localization and interplay between motors in living cells do not exist. Here, we generated a library of 243 amino- and carboxy-terminally tagged mouse and human bacterial artificial chromosome transgenes to establish 227 stably transfected HeLa cell lines, 15 mouse embryonic stem cell lines and 1 transgenic mouse line. The cells were characterized by expression and localization analyses and further investigated by affinity-purification mass spectrometry, identifying 191 candidate protein-protein interactions. We illustrate the power of this resource in two ways. First, by characterizing a network of interactions that targets CEP170 to centrosomes, and second, by showing that kinesin light-chain heterodimers bind conventional kinesin in cells. Our work provides a set of validated resources and candidate molecular pathways to investigate motor protein function across cell lineages.
Edens, Brittany M.; Miller, Nimrod; Ma, Yong-Chao
Selective motor neuron degeneration is a hallmark of amyotrophic lateral sclerosis (ALS). Around 10% of all cases present as familial ALS (FALS), while sporadic ALS (SALS) accounts for the remaining 90%. Diverse genetic mutations leading to FALS have been identified, but the underlying causes of SALS remain largely unknown. Despite the heterogeneous and incompletely understood etiology, different types of ALS exhibit overlapping pathology and common phenotypes, including protein aggregation and mitochondrial deficiencies. Here, we review the current understanding of mechanisms leading to motor neuron degeneration in ALS as they pertain to disrupted cellular clearance pathways, ATP biogenesis, calcium buffering and mitochondrial dynamics. Through focusing on impaired autophagic and mitochondrial functions, we highlight how the convergence of diverse cellular processes and pathways contributes to common pathology in motor neuron degeneration. PMID:26973461
Fernandes, Valter R.; Ribeiro, Michelle L. Scipião; Melo, Thais; de Tarso Maciel-Pinheiro, Paulo; Guimarães, Thiago T.; Araújo, Narahyana B.; Ribeiro, Sidarta; Deslandes, Andréa C.
The relationship between exercise and cognition is an important topic of research that only recently began to unravel. Here, we set out to investigate the relation between motor skills, cognitive function, and school performance in 45 students from 8 to 14 years of age. We used a cross-sectional design to evaluate motor coordination (Touch Test Disc), agility (Shuttle Run Speed—running back and forth), school performance (Academic Achievement Test), the Stroop test, and six sub-tests of the Wechsler Intelligence Scale for Children-IV (WISC-IV). We found, that the Touch Test Disc was the best predictor of school performance (R2 = 0.20). Significant correlations were also observed between motor coordination and several indices of cognitive function, such as the total score of the Academic Achievement Test (AAT; Spearman's rho = 0.536; p ≤ 0.001), as well as two WISC-IV sub-tests: block design (R = −0.438; p = 0.003) and cancelation (rho = −0.471; p = 0.001). All the other cognitive variables pointed in the same direction, and even correlated with agility, but did not reach statistical significance. Altogether, the data indicate that visual motor coordination and visual selective attention, but not agility, may influence academic achievement and cognitive function. The results highlight the importance of investigating the correlation between physical skills and different aspects of cognition. PMID:27014130
Choi, Chan-Il; Yoo, Ki Hyun; Qasim Hussaini, Syed Mohammed; Tak Jeon, Byeong; Welby, John; Gan, Haiyun; Scarisbrick, Isobel A.; Zhang, Zhiguo; Baker, Darren J.; van Deursen, Jan M.; Rodriguez, Moses; Jang, Mi-Hyeon
Myelination, the process by which oligodendrocytes form the myelin sheath around axons, is key to axonal signal transduction and related motor function in the central nervous system (CNS). Aging is characterized by degenerative changes in the myelin sheath, although the molecular underpinnings of normal and aberrant myelination remain incompletely understood. Here we report that axon myelination and related motor function are dependent on BubR1, a mitotic checkpoint protein that has been linked to progeroid phenotypes when expressed at low levels and healthy lifespan when overabundant. We found that oligodendrocyte progenitor cell proliferation and oligodendrocyte density is markedly reduced in mutant mice with low amounts of BubR1 (BubR1H/H mice), causing axonal hypomyelination in both brain and spinal cord. Expression of essential myelin-related genes such as MBP and PLP1 was significantly reduced in these tissues. Consistent with defective myelination, BubR1H/H mice exhibited various motor deficits, including impaired motor strength, coordination, and balance, irregular gait patterns and reduced locomotor activity. Collectively, these data suggest that BubR1 is a key determinant of oligodendrocyte production and function and provide a molecular entry point to understand age-related degenerative changes in axon myelination. PMID:27922816
Moldovan, Mihai; Rosberg, Mette Romer; Alvarez, Susana; Klein, Dennis; Martini, Rudolf; Krarup, Christian
Accumulating myelin abnormalities and conduction slowing occur in peripheral nerves during aging. In mice deficient of myelin protein P0, severe peripheral nervous system myelin damage is associated with ectopic expression of Nav1.8 voltage-gated Na(+) channels on motor axons aggravating the functional impairment. The aim of the present study was to investigate the effect of regular aging on motor axon function with particular emphasis on Nav1.8. We compared tibial nerve conduction and excitability measures by threshold tracking in 12 months (mature) and 20 months (aged) wild-type (WT) mice. With aging, deviations during threshold electrotonus were attenuated and the resting current-threshold slope and early refractoriness were increased. Modeling indicated that, in addition to changes in passive membrane properties, motor fibers in aged WT mice were depolarized. An increased Nav1.8 isoform expression was found by immunohistochemistry. The depolarizing excitability features were absent in Nav1.8 null mice, and they were counteracted in WT mice by a Nav1.8 blocker. Our data suggest that alteration in voltage-gated Na(+) channel isoform expression contributes to changes in motor axon function during aging.
Alia, Claudia; Spalletti, Cristina; Lai, Stefano; Panarese, Alessandro; Micera, Silvestro; Caleo, Matteo
A deeper understanding of post-stroke plasticity is critical to devise more effective pharmacological and rehabilitative treatments. The GABAergic system is one of the key modulators of neuronal plasticity, and plays an important role in the control of “critical periods” during brain development. Here, we report a key role for GABAergic inhibition in functional restoration following ischemia in the adult mouse forelimb motor cortex. After stroke, the majority of cortical sites in peri-infarct areas evoked simultaneous movements of forelimb, hindlimb and tail, consistent with a loss of inhibitory signalling. Accordingly, we found a delayed decrease in several GABAergic markers that accompanied cortical reorganization. To test whether reductions in GABAergic signalling were causally involved in motor improvements, we treated animals during an early post-stroke period with a benzodiazepine inverse agonist, which impairs GABAA receptor function. We found that hampering GABAA signalling led to significant restoration of function in general motor tests (i.e., gridwalk and pellet reaching tasks), with no significant impact on the kinematics of reaching movements. Improvements were persistent as they remained detectable about three weeks after treatment. These data demonstrate a key role for GABAergic inhibition in limiting motor improvements after cortical stroke. PMID:27897203
Morimoto, Yusuke V; Minamino, Tohru
The bacterial flagellum is a locomotive organelle that propels the bacterial cell body in liquid environments. The flagellum is a supramolecular complex composed of about 30 different proteins and consists of at least three parts: a rotary motor, a universal joint, and a helical filament. The flagellar motor of Escherichia coli and Salmonella enterica is powered by an inward-directed electrochemical potential difference of protons across the cytoplasmic membrane. The flagellar motor consists of a rotor made of FliF, FliG, FliM and FliN and a dozen stators consisting of MotA and MotB. FliG, FliM and FliN also act as a molecular switch, enabling the motor to spin in both counterclockwise and clockwise directions. Each stator is anchored to the peptidoglycan layer through the C-terminal periplasmic domain of MotB and acts as a proton channel to couple the proton flow through the channel with torque generation. Highly conserved charged residues at the rotor-stator interface are required not only for torque generation but also for stator assembly around the rotor. In this review, we will summarize our current understanding of the structure and function of the proton-driven bacterial flagellar motor.
Morimoto, Yusuke V.; Minamino, Tohru
The bacterial flagellum is a locomotive organelle that propels the bacterial cell body in liquid environments. The flagellum is a supramolecular complex composed of about 30 different proteins and consists of at least three parts: a rotary motor, a universal joint, and a helical filament. The flagellar motor of Escherichia coli and Salmonella enterica is powered by an inward-directed electrochemical potential difference of protons across the cytoplasmic membrane. The flagellar motor consists of a rotor made of FliF, FliG, FliM and FliN and a dozen stators consisting of MotA and MotB. FliG, FliM and FliN also act as a molecular switch, enabling the motor to spin in both counterclockwise and clockwise directions. Each stator is anchored to the peptidoglycan layer through the C-terminal periplasmic domain of MotB and acts as a proton channel to couple the proton flow through the channel with torque generation. Highly conserved charged residues at the rotor–stator interface are required not only for torque generation but also for stator assembly around the rotor. In this review, we will summarize our current understanding of the structure and function of the proton-driven bacterial flagellar motor. PMID:24970213
Tinazzi, Michele; Farina, Simona; Tamburin, Stefano; Facchini, Stefano; Fiaschi, Antonio; Restivo, Domenico; Berardelli, Alfredo
We evaluated motor evoked potentials (MEPs) and duration of the cortical silent period (CSP) from the right first dorsal interosseous (FDI) muscle to transcranial magnetic stimulation (TMS) of the left motor cortex in ten healthy subjects performing different manual tasks. They abducted the index finger alone, pressed a strain gauge with the thumb and index finger in a pincer grip, and squeezed a 4-cm brass cylinder with all digits in a power grip. The level of FDI EMG activity across tasks was kept constant by providing subjects with acoustic-visual feedback of their muscle activity. The TMS elicited larger amplitude FDI MEPs during pincer and power grip than during the index finger abduction task, and larger amplitude MEPs during pincer gripping than during power gripping. The CSP was shorter during pincer and power grip than during the index finger abduction task and shorter during power gripping than during pincer gripping. These results suggest excitatory and inhibitory task-dependent changes in the motor cortex. Complex manual tasks (pincer and power gripping) elicit greater motor cortical excitation than a simple task (index finger abduction) presumably because they activate multiple synergistic muscles thus facilitating corticomotoneurons. The finger abduction task probably yielded greater motor cortical inhibition than the pincer and power tasks because muscles uninvolved in the task activated the cortical inhibitory circuit. Increased cortical excitatory and inhibitory functions during precision tasks (pincer gripping) probably explain why MEPs have larger amplitudes and CSPs have longer durations during pincer gripping than during power gripping.
Introduction The aim of the present study was to evaluate color perception thresholds and relate them to the degree of motor impairment in children with spastic cerebral palsy (SCP). Methods Binocular and monocular chromaticity discrimination thresholds were estimated for the protan, deutan, and tritan color confusion axes in 43 SCP children aged 6–15 years who were classified as tetraplegic (n = 12), diplegic (n = 16), and hemiplegic (n = 15) without ophthalmological complaints. Motor impairment was rated according to the Gross Motor Function Classification System (GMFCS) in five levels of severity. Results Analysis of variance showed significantly reduced discrimination in tetraplegic children (p < 0.001) compared with the diplegic, hemiplegic, and control groups. We also found a positive correlation between chromaticity discrimination thresholds and GMFCS ratings in all of the groups. Discussion Chromaticity discrimination thresholds measured psychophysically were reduced for all three color confusion axis in tetraplegic children compared with normal children. Diplegic and hemiplegic children had similar results as normal children. The finding of a correlation between quantified motor impairment and color discrimination losses in SCP patients is a new observation that might help elucidate the causes of color perception loss in these patients. Visual information is essential for the rehabilitation of CP children. Knowledge of the degree of correlation between vision and motor impairment is valuable when planning a rehabilitation program. PMID:24961924
Cooke, Dylan F.; Padberg, Jeffrey; Zahner, Tony
Despite extraordinary diversity in the rodent order, studies of motor cortex have been limited to only 2 species, rats and mice. Here, we examine the topographic organization of motor cortex in the Eastern gray squirrel (Sciurus carolinensis) and cortical connections of motor cortex in the California ground squirrel (Spermophilus beecheyi). We distinguish a primary motor area, M1, based on intracortical microstimulation (ICMS), myeloarchitecture, and patterns of connectivity. A sensorimotor area between M1 and the primary somatosensory area, S1, was also distinguished based on connections, functional organization, and myeloarchitecture. We term this field 3a based on similarities with area 3a in nonrodent mammals. Movements are evoked with ICMS in both M1 and 3a in a roughly somatotopic pattern. Connections of 3a and M1 are distinct and suggest the presence of a third far rostral field, termed “F,” possibly involved in motor processing based on its connections. We hypothesize that 3a is homologous to the dysgranular zone (DZ) in S1 of rats and mice. Our results demonstrate that squirrels have both similar and unique features of M1 organization compared with those described in rats and mice, and that changes in 3a/DZ borders appear to have occurred in both lineages. PMID:22021916
Rao, Ashwini K; Mazzoni, Pietro; Wasserman, Paula; Marder, Karen
The purpose of this study was to examine longitudinal change in gait and motor function in pre-manifest Huntington's disease (HD).We examined ten pre-manifest subjects at baseline, one and five years. Quantitative gait data were collected with an electronic mat (GAITRite®). We analyzed measures related to speed (velocity, step length, cadence), asymmetry (step length difference), dynamic balance (percent time in double support, support base) and variability in stride length and swing time. Motor function was assessed with the motor component of the Unified Huntington's Disease Rating Scale.Gait velocity decreased (p=0.001), whereas step length difference (p=0.006), stride length variability (p=0.0001) and swing time variability increased (p=0.0001) from baseline to year five. Step length difference (p<0.05) and swing time variability (p<0.05) increased marginally in one year from baseline. UHDRS Total motor score increased over five years (p=0.003), though the increase in one year was not significant (p=0.053). Of the individual motor domain scores (eye, hand movements, gait and balance, chorea) only dystonia worsened over five years (p=0.02). Total motor score (r2= 0.49, p<0.001) and swing time variability (r2= 0.22, p<0.009) were correlated with estimated years to diagnosis.Our results present the longest longitudinal follow up of gait in pre-manifest HD thus far. Despite the small sample size, quantitative gait analysis was able to detect changes in gait speed, symmetry and variability. Swing time variability was particularly important because it increased in one year from baseline and was correlated with estimated time to diagnosis. Our results highlight the importance of predictive outcomes such as gait variability using quantitative analysis.
... esophagus. These may include household cleaners, lye, disc batteries, or battery acid. Treatment of esophageal varices Symptoms Symptoms may ... Prognosis) The stricture may come back in the future. This would require a repeat dilation. Possible Complications ...
... layers of tissue , including mucous membrane , muscle, and connective tissue . Esophageal cancer starts on the inside lining of ... and spread into the muscle layer or the connective tissue layer of the esophagus wall. The cancer cells ...
... consortium of three translational research centers studying the origins and pathogenesis of esophageal cancer, with the ultimate goal of improving patient outcomes and decreasing the burden of the disease. One center is studying the genetic basis of ...
Otsuka, Shintaro; Konno, Kohtarou; Abe, Manabu; Motohashi, Junko; Kohda, Kazuhisa; Sakimura, Kenji; Watanabe, Masahiko; Yuzaki, Michisuke
The cerebellum is thought to be involved in cognitive functions in addition to its well established role in motor coordination and motor learning in humans. Cerebellin 1 (Cbln1) is predominantly expressed in cerebellar granule cells and plays a crucial role in the formation and function of parallel fiber-Purkinje cell synapses. Although genes encoding Cbln1 and its postsynaptic receptor, the delta2 glutamate receptor (GluD2), are suggested to be associated with autistic-like traits and many psychiatric disorders, whether such cognitive impairments are caused by cerebellar dysfunction remains unclear. In the present study, we investigated whether and how Cbln1 signaling is involved in non-motor functions in adult mice. We show that acquisition and retention/retrieval of cued and contextual fear memory were impaired in Cbln1-null mice. In situ hybridization and immunohistochemical analyses revealed that Cbln1 is expressed in various extracerebellar regions, including the retrosplenial granular cortex and the hippocampus. In the hippocampus, Cbln1 immunoreactivity was present at the molecular layer of the dentate gyrus and the stratum lacunosum-moleculare without overt mRNA expression, suggesting that Cbln1 is provided by perforant path fibers. Retention/retrieval, but not acquisition, of cued and contextual fear memory was impaired in forebrain-predominant Cbln1-null mice. Spatial learning in the radial arm water maze was also abrogated. In contrast, acquisition of fear memory was affected in cerebellum-predominant Cbln1-null mice. These results indicate that Cbln1 in the forebrain and cerebellum mediates specific aspects of fear conditioning and spatial memory differentially and that Cbln1 signaling likely regulates motor and non-motor functions in multiple brain regions.
Chiaretti, Antonio; Rendeli, Claudia; Antonelli, Alessia; Barone, Giuseppe; Focarelli, Benedetta; Tabacco, Fabrizia; Massimi, Luca; Ausili, Emanuele
Glial-derived neurotrophic factor (GDNF) is one of several powerful survival factors for spinal motoneurons that play a key role in sprouting, synaptic plasticity, and reorganization after spinal cord damage. The aim of this study was to investigate the expression of GDNF in plasma of children with spina bifida (SB) and to determine its correlation with both the severity of spinal cord damage and the motor function of these patients. To measure the GDNF expression, we collected plasma samples from 152 children with SB and in 149 matched controls. Endogenous GDNF levels were quantified using a two-site immuno-enzymatic assay. The statistical analysis was performed using the Mann-Whitney two-tailed two-sample test. In children with SB the mean levels of GDNF (131.2 +/- 69.6 pg/mL) were significantly higher (p < 0.001) with respect to the mean levels of the control group (102.7 +/- 6.8 pg/mL). Moreover, in open SB, the GDNF levels (139.2 +/- 81.1 pg/mL) were significantly higher (p < 0.05) with respect to closed SB (117.2 +/- 41.3 pg/mL). In terms of the motor function of patients, we found that in children with poorer motor function, the GDNF levels (134.5 +/- 67.4 pg/mL) were higher, but not statistically significant (p < 0.1), than in patients with better motor outcome (122.3 +/- 72.2 pg/mL). Our study demonstrates GDNF over-expression in children with SB. This upregulation is significantly associated with the severity of spinal cord damage in SB patients and appears to correlate with poor motor function of children, representing an important biochemical marker of the severity of spine injury.
The major goal of this thesis was to design and develop an actuator, which is capable of producing translational and rotary output motions in a compact structure with simple driving conditions, for the needs of small-scale actuators for micro robotic systems. Piezoelectric ultrasonic motors were selected as the target actuator schemes because of their unbeatable characteristics in the meso-scale range, which covers the structure sizes from hundred micrometers to ten millimeters and with operating ranges from few nanometers to centimeters. In order to meet the objectives and the design constraints, a number of key research tasks had to be undertaken. The design constraints and objectives were so stringent and entangled that none of the existing methods in literature could solve the research problems individually. Therefore, several unique methods were established to accomplish the research objectives. The methods produced novel solutions at every stage of design, development and modeling of the multi functional micro ultrasonic motor. Specifically, an ultrasonic motor utilizing slanted ceramics on a brass rod was designed. Because of the unique slanted ceramics design, longitudinal and torsional mode vibration modes could be obtained on the same structure. A ring shaped mobile element was loosely fitted on the metal rod stator. The mobile element moved in translational or rotational, depending on whether the vibration mode was longitudinal or torsional. A new ultrasonic motor drive method was required because none of the existing ultrasonic motor drive techniques were able to provide both output modes in a compact and cylindrical structure with the use of single drive source. By making use of rectangular wave drive signals, saw-tooth shaped displacement profile could be obtained at longitudinal and torsional resonance modes. Thus, inheriting the operating principle of smooth impact drive method, a new resonance type inertial drive was introduced. This new technique
Ravi, N; Stuart, R C; Byrne, P J; Reynolds, J V
The most common type of esophageal dysfunction associated with chest pain is gastroesophageal reflux, which may be induced by exercise. The effect of exercise on esophageal function has mainly been investigated in normal subjects or trained athletes. Few studies have investigated exercise and esophageal motility disorders. One hundred and thirty-five patients underwent ambulatory esophageal manometry and pH monitoring, before, during and immediately after moderate exercise. Patients were divided into four groups: Normal, nutcracker, diffuse spasm and gastroesophageal reflux disease (GERD). Ambulatory manometry and pH were monitored while exercising on a treadmill during which standardized boluses of water were administered. Nutcracker and diffuse spasm patients demonstrated a significant fall in esophageal wave amplitude during exercise compared to controls, which returned rapidly to pre exercise values after resting. There was no evidence of acid reflux in the non-reflux groups during exercise. Reflux was noted in 13 patients with GERD during exercise, none of whom had evidence of reflux at the onset of exercise. When these patients were classified by reflux type, the majority, 11 patients, were found to come from the combined or supine reflux group. Esophageal amplitude in nutcracker esophagus does not increase during moderate exercise. Moderate exercise provokes reflux in GERD patients with combined or supine reflux.
staining for major basic protein in esophageal tissue (arrowheads) in WT than IL21R-/- mice (A) is quantified morphometrically in (B). Quantitative PCR... morphometric analysis was used to measure IL21 receptor expression in patient esophageal biopsies. RESULTS: A number of genetic variants on chromosome 4q26-27...variants in the locus. Immunofluorescent microscopy and morphometric analysis demonstrate a marked increase in IL21 receptor- expressing cells within
Noyer, C M; Simon, D
This article focused on the approach to oral and esophageal disorders in patients with AIDS. Most of these disorders respond to various therapeutic regimens. Some of the oral complications can be prevented with dental prophylaxis, whereas recurrent esophageal disease in some patients may require long-term suppressive therapy. As patients with AIDS live longer with lower CD4 counts, gastroenterologists need to become familiar with the approach to and management of the more common lesions of the mouth and esophagus.
Tomata, Yasutake; Kogure, Mana; Sugawara, Yumi; Watanabe, Takashi; Asaka, Tadayoshi; Tsuji, Ichiro
Objective Previous studies have reported that elderly victims of natural disasters might be prone to a subsequent decline in motor function. Victims of the Great East Japan Earthquake (GEJE) relocated to a wide range of different types of housing. As the evacuee lifestyle varies according to the type of housing available to them, their degree of motor function loss might also vary accordingly. However, the association between postdisaster housing type and loss of motor function has never been investigated. The present study was conducted to investigate the association between housing type after the GEJE and loss of motor function in elderly victims. Methods We conducted a prospective observational study of 478 Japanese individuals aged ≥65 years living in Miyagi Prefecture, one of the areas most significantly affected by the GEJE. Information on housing type after the GEJE, motor function as assessed by the Kihon checklist and other lifestyle factors was collected by interview and questionnaire in 2012. Information on motor function was then collected 1 year later. The multiple logistic regression model was used to estimate the multivariate adjusted ORs of motor function loss. Results We classified 53 (11.1%) of the respondents as having loss of motor function. The multivariate adjusted OR (with 95% CI) for loss of motor function among participants who were living in privately rented temporary housing/rental housing was 2.62 (1.10 to 6.24) compared to those who had remained in the same housing as that before the GEJE, and this increase was statistically significant. Conclusions The proportion of individuals with loss of motor function was higher among persons who had relocated to privately rented temporary housing/rental housing after the GEJE. This result may reflect the influence of a move to a living environment where few acquaintances are located (lack of social capital). PMID:27810976
Bae, Jong Seok; Ferguson, Michele; Tan, Rachel; Mioshi, Eneida; Simon, Neil; Burrell, James; Vucic, Steve; Hodges, John R.; Kiernan, Matthew C
Background and Purpose This study investigated the structural and functional changes in the motor system in amyotrophic lateral sclerosis (ALS; n=25) and behavioral-variant fronto-temporal dementia (bvFTD; n=17) relative to healthy controls (n=37). Methods Structural changes were examined using a region-of-interest approach, applying voxel-based morphometry for gray-matter changes and diffusion tensor imaging for white-matter changes. Functional changes in the motor system were elucidated using threshold-tracking transcranial magnetic stimulation (TMS) measurements of upper motor-neuron excitability. Results The structural analyses showed that in ALS there were more white-matter changes in the corticospinal and motor-cortex regions and more gray-matter changes in the cerebellum in comparison to controls. bvFTD showed substantial gray- and white-matter changes across virtually all motor-system regions compared to controls, although the brainstem was affected less than the other regions. Direct comparisons across patient groups showed that the gray- and white-matter motor-system changes inclusive of the motor cortex were greater in bvFTD than in ALS. By contrast, the functional integrity of the motor system was more adversely affected in ALS than in bvFTD, with both patient groups showing increased excitability of upper motor neurons compared to controls. Conclusions Cross-correlation of structural and functional data further revealed a neural dissociation of different motor-system regions and tracts covarying with the TMS excitability across both patient groups. The structural and functional motor-system integrities appear to be dissociated between ALS and bvFTD, which represents useful information for the diagnosis of motor-system changes in these two disorders. PMID:26932257
Lin, Eric W.; Karakasheva, Tatiana A.; Hicks, Philip D.; Bass, Adam J.; Rustgi, Anil K.
Esophageal cancer is a deadly disease, ranking sixth among all cancers in mortality. Despite incremental advances in diagnostics and therapeutics, esophageal cancer still carries a poor prognosis, and thus there remains a need to elucidate the molecular mechanisms underlying this disease. There is accumulating evidence that a comprehensive understanding of the molecular composition of esophageal cancer requires attention to not only tumor cells but also the tumor microenvironment, which contains diverse cell populations, signaling factors, and structural molecules that interact with tumor cells and support all stages of tumorigenesis. In esophageal cancer, environmental exposures can trigger chronic inflammation, which leads to constitutive activation of pro-inflammatory signaling pathways that promote survival and proliferation. Anti-tumor immunity is attenuated by cell populations such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), as well as immune checkpoints like programmed death-1 (PD-1). Other immune cells such as tumor-associated macrophages can have other pro-tumorigenic functions, including the induction of angiogenesis and tumor cell invasion. Cancer-associated fibroblasts secrete growth factors and alter the extracellular matrix (ECM) to create a tumor niche and enhance tumor cell migration and metastasis. Further study of how these TME components relate to the different stages of tumor progression in each esophageal cancer subtype will lead to development of novel and specific TME-targeting therapeutic strategies, which offer considerable potential especially in the setting of combination therapy. PMID:26923327
Suzuki, Makoto; Kuwano, Hiroyuki
In this report, we describe the esophageal atresia in terms of current surgical management on the basis of our experience and literatures. Traditionally, infants with esophageal atresia have presented shortly after birth because of an inability to pass an orogastric tube, respiratory distress, or an inability to tolerate feeding. And also, an isolated trachea-esophageal fistula (TEF) usually cases coughing, recurrent pneumonia, or choking during feedings. To ignore these symptoms is to risk a delayed diagnosis. The condition may be associated with other major congenital anomalies such as those seen in the vertebral, anal, cardiac, tracheo-esophageal, renal/radial (VACTER) association, or it may be an isolated defect. Therapeutic strategies for esophageal atresia are a prevention of pulmonary complication by TEF closing and an early establishment of enteral alimentation. We promptly repair healthy infants without performing a gastrostomy and delay repair in infants with high-risk factors such as associated severe cardiac anomaly and respiratory insufficiency. Esophageal atresia has been classically approached through a thoracotomy. The disadvantages of such a thoracotomy have been recognized for a long time, for example winged scapula, elevation of fixation of shoulder, asymmetry of the chest wall, rib fusion, scoliosis, and breast and pectoral muscle maldevelopment. To avoid such disadvantages, thoracoscopic repair was recently reported.
Helmich, Rick C; Siebner, Hartwig R; Bakker, Maaike; Münchau, Alexander; Bloem, Bastiaan R
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that can produce lasting changes in excitability and activity in cortical regions underneath the stimulation coil (local effect), but also within functionally connected cortical or subcortical regions (remote effects). Since the clinical presentation of Parkinson's disease (PD) is related to abnormal neuronal activity within the basal ganglia and cortical regions, including the primary motor cortex, the premotor cortex and the prefrontal cortex, several studies have used rTMS to improve brain function in PD. Here, we review the studies that have investigated the possible therapeutic effects of rTMS on mood and motor function in PD patients. We highlight some methodological inconsistencies and problems, including the difficulty to define the most effective protocol for rTMS or to establish an appropriate placebo condition. We finally propose future directions of research that may help to improve the therapeutic efficacy of rTMS in PD.
Ota, Keiji; Shinya, Masahiro; Kudo, Kazutoshi
For optimal action planning, the gain/loss associated with actions and the variability in motor output should both be considered. A number of studies make conflicting claims about the optimality of human action planning but cannot be reconciled due to their use of different movements and gain/loss functions. The disagreement is possibly because of differences in the experimental design and differences in the energetic cost of participant motor effort. We used a coincident timing task, which requires decision making with constant energetic cost, to test the optimality of participant's timing strategies under four configurations of the gain function. We compared participant strategies to an optimal timing strategy calculated from a Bayesian model that maximizes the expected gain. We found suboptimal timing strategies under two configurations of the gain function characterized by asymmetry, in which higher gain is associated with higher risk of zero gain. Participants showed a risk-seeking strategy by responding closer than optimal to the time of onset/offset of zero gain. Meanwhile, there was good agreement of the model with actual performance under two configurations of the gain function characterized by symmetry. Our findings show that human ability to make decisions that must reflect uncertainty in one's own motor output has limits that depend on the configuration of the gain function. PMID:26236227
ASAHI, Takashi; NAKAMICHI, Naomi; TAKAIWA, Akiko; KASHIWAZAKI, Daina; KOH, Masaki; DOUGU, Nobuhiro; TAKASHIMA, Shutaro; TANAKA, Kortaro; KURODA, Satoshi
It is still unclear whether deep brain stimulation targeted to the bilateral subthalamic nucleus (STN-DBS) affects cognitive function in Parkinson's disease (PD). This prospective study was aimed to systemically evaluate the impact of bilateral STN-DBS on motor and cognitive functions in patients with PD. This study included totally 11 Japanese patients with medically intolerant PD. Neurological and cognitive status was precisely evaluated before and 1 year after bilateral STN-DBS, using unified Parkinson's disease rating scale (UPDRS), levodopa equivalent doses, mini-mental state examination (MMSE), Japanese adult reading test (JART), repeatable battery for the assessment of neuropsychological status (RBANS), and Wechsler adult intelligence scale-revised (WAIS-R). Preoperative RBANS and WAIS-R identified cognitive dysfunction that could not be detected by MMSE and JART. Before surgery, PD patients had significantly impaired immediate memory and attention. Motor function significantly improved 1 year after bilateral STN-DBS. Bilateral STN-DBS did not affect any score on cognitive examinations. However, postoperative improvements of total score on RBANS and performance intelligence quotient (PIQ) scores on WAIS-R were closely related to those of UPDRS part III off (R2 = 0.61, P < 0.01; R2 = 0.39, P < 0.05, respectively). These findings strongly suggest that bilateral STN-DBS may significantly improve cognitive function in a certain subgroup of patients whose therapeutic effects on motor function are prominent. PMID:24872253
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.
Van Teeffelen, Jurgen W G E; Segal, Steven S
The effect of motor unit recruitment on functional vasodilatation was investigated in hamster retractor muscle. Recruitment (i.e. peak tension) was controlled with voltage applied to the spinal accessory nerve (high = maximum tension; intermediate = ∼50% maximum; low = ∼25% maximum). Vasodilatory responses (diameter × time integral, DTI) to rhythmic contractions (1 per 2 s for 65 s) were evaluated in first, second and third orderarterioles and in feed arteries. Reciprocal changes in duty cycle (range, 2·5–25 %) effectively maintained the total active tension (tension × time integral, TTI) constant across recruitment levels. With constant TTI and stimulation frequency (40 Hz), DTI in all vessels increased with motor unit recruitment. DTI increased from distal arterioles up through proximal feed arteries. To determine whether the effect of recruitment on DTI was due to increased peak tension, the latter was controlled with stimulation frequency (15, 20 and 40 Hz) during maximum (high) recruitment. With constant TTI, DTI then decreased as peak tension increased. To explore the interaction between recruitment and duty cycle on DTI, each recruitment level was applied at 2.5, 10 and 20 % duty cycle (at 40 Hz). For a given increase in TTI, recruitment had a greater effect on DTI than did duty cycle. Functional vasodilatation in response to rhythmic contractions is facilitated by motor unit recruitment. Thus, vasodilatory responses are determined not only by the total tension produced, but also by the number of active motor units. PMID:10747197
Aylward, Elizabeth H.; Harrington, Deborah L.; Mills, James A.; Nopoulos, Peggy C.; Ross, Christopher A.; Long, Jeffrey D.; Liu, Dawei; Westervelt, Holly K.; Paulsen, Jane S.
Background Neuroimaging studies suggest that volumetric MRI measures of specific brain structures may serve as excellent biomarkers in future clinical trials of Huntington disease (HD). Objective Demonstration of the clinical significance of these measures is an important step in determining their appropriateness as potential outcome measures. Methods Measures of gray- and white-matter lobular volumes and subcortical volumes (caudate, putamen, globus pallidus, thalamus, nucleus accumbens, hippocampus) were obtained from MRI scans of 516 individuals who tested positive for the HD gene expansion, but were not yet exhibiting signs or symptoms severe enough to warrant diagnosis (“pre-HD”). MRI volumes (corrected for intracranial volume) were correlated with cognitive, motor, psychiatric, and functional measures known to be sensitive to subtle changes in pre-HD. Results Caudate, putamen, and globus pallidus volumes consistently correlated with cognitive and motor, but not psychiatric or functional measures in pre-HD. Volumes of white matter, nucleus accumbens, and thalamus, but not cortical gray matter, also correlated with some of the motor and cognitive measures. Conclusions Results of regression analyses suggest that volumes of basal ganglia structures contributed more highly to the prediction of most motor and cognitive variables than volumes of other brain regions. These results support the use of volumetric measures, especially of the basal ganglia, as outcome measures in future clinical trials in pre-HD. Results may also assist investigators in selecting the most appropriate measures for treatment trials that target specific clinical features or regions of neuropathology. PMID:25062732
Chen, Yu-Wen; Chiu, Chong-Chi; Liu, Kuo-Sheng; Hung, Ching-Hsia; Wang, Jhi-Joung
Although memantine blocks sodium currents and produces local skin anesthesia, spinal anesthesia with memantine is unknown. The purpose of the study was to evaluate the local anesthetic effect of memantine in spinal anesthesia and its comparison with a widely used local anesthetic lidocaine. After intrathecally injecting the rats with five doses of each drug, the dose-response curves of memantine and lidocaine were constructed. The potencies of the drugs and durations of spinal anesthetic effects on motor function, proprioception, and nociception were compared with those of lidocaine. We showed that memantine produced dose-dependent spinal blockades in motor function, proprioception, and nociception. On a 50% effective dose (ED50 ) basis, the rank of potency was lidocaine greater than memantine (P < 0.05 for the differences). At the equipotent doses (ED25 , ED50 , ED75 ), the block duration produced by memantine was longer than that produced by lidocaine (P < 0.05 for the differences). Memantine, but not lidocaine, displayed more sensory/nociceptive block than motor block. The preclinical data demonstrated that memantine is less potent than lidocaine, whereas memantine produces longer duration of spinal anesthesia than lidocaine. Memantine shows a more sensory-selective action over motor blockade.
Bala, Gustav; Katić, Ratko
The study included a sample of 333 preschool children (162 male and 171 female) at the time of school enrolment. Study subjects were recruited from the population of children in kindergartens in the cities of Novi Sad, Sombor, Sremska Mitrovica and Backa Palanka (Province of Voivodina, Serbia). Eight anthropometric variables, seven motor variables and one cognitive variable were analyzed to identify quantitative and qualitative sex differences in anthropometric characteristics, motor and cognitive functioning. Study results showed statistically significant sex differences in anthropometric characteristics and motor abilities in favor of male children, whereas no such difference was recorded in cognitive functioning. Sex differences found in morphological and motor spaces contributed to structuring proper general factors according to space and sex. Somewhat stronger structures were observed in male children. The cognitive aspect of functioning yielded better correlation with motor functioning in female than in male children. Motor functioning correlated better with morphological growth and development in male children, whereas cognitive functioning was relatively independent. These results are not fully in accordance with the current concept of general conditions in preschool children, nor they fully confirm the theory of integral development of children, hence they should be re-examined in future studies. Although these study results cannot be applied to sports practice in general, since we believe that it is too early for preschool children to take up sports and sport competitions, they are relevant for pointing to the need of developing general motor ability and motor behavior in preschool children.
Wu, Xiaona; Li, Zhensheng; Liu, Xiaoyan; Peng, Haiyan; Huang, Yongjun; Luo, Gaoquan; Peng, Kairun
Major ozonated autohemotherapy is classically used in treating ischemic disorder of the lower limbs. In the present study, we performed major ozonated autohemotherapy treatment in patients with acute cerebral infarction, and assessed outcomes according to the U.S. National Institutes of Health Stroke Score, Modified Rankin Scale, and transcranial magnetic stimulation motor-evoked potential. Compared with the control group, the clinical total effective rate and the cortical potential rise rate of the upper limbs were significantly higher, the central motor conduction time of upper limb was significantly shorter, and the upper limb motor-evoked potential amplitude was significantly increased, in the ozone group. In the ozone group, the National Institutes of Health Stroke Score was positively correlated with the central motor conduction time and the motor-evoked potential amplitude of the upper limb. Central motor conduction time and motor-evoked potential amplitude of the upper limb may be effective indicators of motor-evoked potentials to assess upper limb motor function in cerebral infarct patients. Furthermore, major ozonated autohemotherapy may promote motor function recovery of the upper limb in patients with acute cerebral infarction. PMID:25206688
Fu, Trista J; Lincoln, Alan J; Bellugi, Ursula; Searcy, Yvonne M
Williams syndrome (WS) is associated with deficits in adaptive behavior and an uneven adaptive profile. This study investigated the association of intelligence, visual-motor functioning, and personality characteristics with the adaptive behavior in individuals with WS. One hundred individuals with WS and 25 individuals with developmental disabilities of other etiologies were included in this study. This study found that IQ and visual-motor functioning significantly predicted adaptive behavior in individuals of WS. Visual-motor functioning especially predicted the most amount of unique variance in overall adaptive behavior and contributed to the variance above and beyond that of IQ. Present study highlights the need for interventions that address visual-motor and motor functioning in individuals with WS.
Wilson, Ashlea; Kavanaugh, Abi; Moher, Rosemarie; McInroy, Megan; Gupta, Neena; Salbach, Nancy M.; Wright, F. Virginia
The aim was to develop a Challenge Module (CM) as a proposed adjunct to the Gross Motor Function Measure for children with cerebral palsy who have high-level motor function. Items were generated in a physiotherapist (PT) focus group. Item reduction was based on PTs' ratings of item importance and safety via online surveys. The proposed CM items…
Hayashi, Hiroyuki; Nakashima, Daiki; Matsuoka, Hiroka; Iwai, Midori; Nakamura, Shugo; Kubo, Ayumi; Tomiyama, Naoki
ABSTRACT Exercise, such as cardiovascular fitness training, has been shown to have utility in improving executive function but is difficult for older adults with low mobility to perform. Accordingly, there is interest in the development of regimens other than high mobility exercises for older adults with low mobility. The aim of the present study was to evaluate the association between sensory motor function of the upper limb and executive function in community-dwelling older adults. A cross-sectional study was conducted in 57 right-handed, independent, community-dwelling older adults. Sensory motor function of upper limb, including range of motion, strength, sensation, finger dexterity, and comprehensive hand function was measured in both hands. Executive function was assessed using the Delta Trail Making Test. Multiple regression analysis indicated the finger dexterity of the non-dominant hand as independently associated with executive function (β = –0.414, P < 0.001). The findings of the present study may facilitate the development of exercise regimens for improving executive function that are more suitable for older adults with limited physical fitness levels. As this was a cross-sectional study, further studies are required to validate the efficacy of non-dominant finger dexterity training for improving executive function in older adults. PMID:27578912
Hayashi, Hiroyuki; Nakashima, Daiki; Matsuoka, Hiroka; Iwai, Midori; Nakamura, Shugo; Kubo, Ayumi; Tomiyama, Naoki
Exercise, such as cardiovascular fitness training, has been shown to have utility in improving executive function but is difficult for older adults with low mobility to perform. Accordingly, there is interest in the development of regimens other than high mobility exercises for older adults with low mobility. The aim of the present study was to evaluate the association between sensory motor function of the upper limb and executive function in community-dwelling older adults. A cross-sectional study was conducted in 57 right-handed, independent, community-dwelling older adults. Sensory motor function of upper limb, including range of motion, strength, sensation, finger dexterity, and comprehensive hand function was measured in both hands. Executive function was assessed using the Delta Trail Making Test. Multiple regression analysis indicated the finger dexterity of the non-dominant hand as independently associated with executive function (β = -0.414, P < 0.001). The findings of the present study may facilitate the development of exercise regimens for improving executive function that are more suitable for older adults with limited physical fitness levels. As this was a cross-sectional study, further studies are required to validate the efficacy of non-dominant finger dexterity training for improving executive function in older adults.
Cakar, Engin; Akyuz, Gulseren; Durmus, Oguz; Bayman, Levent; Yagci, Ilker; Karadag-Saygi, Evrim; Gunduz, Osman Hakan
The standardization of patient evaluation and monitoring methods has a special importance in evaluating the effectiveness of therapeutic methods using drugs or rehabilitative techniques in stroke rehabilitation. The aim of this study was to investigate the relationships between clinical instruments and transcranial magnetic stimulation (TMS)-evoked neurophysiological parameters in stroke patients. This study included 22 chronic post-stroke patients who were clinically assessed using the Motricity Index (MI), finger-tapping test (FTT), Motor Activity Log (MAL) 28, Brunnstrom motor staging and Ashworth Scale (ASH). Motor-evoked potential (MEP) latency and amplitude, resting motor threshold (rMT) and central motor conduction time (CMCT) were measured with TMS. Shorter MEP-latency, shorter CMCT, higher motor-evoked potential amplitude, and diminished rMT exhibited significant correlations with clinical measures evaluating motor stage, dexterity, and daily life functionality. rMT exhibited a negative correlation with hand and lower extremity Brunnstrom stages (r = -0.64, r = -0.51, respectively), MI score (r = -0.48), FTT score (r = -0.69), and also with amount of use scale and quality of movement scale of MAL 28 scores (r = -0.61, r = -0.62, respectively). Higher MEP amplitude and diminished rMT showed positive correlations with reduced ASH score (r = -0.65, r = 0.44, respectively). The TMS-evoked neurophysiologic parameters including MEP latency, amplitude, rMT and CMCT generally have positive correlation with clinical measures which evaluate motor stage, dexterity and daily life functionality. Additionally, spasticity has also remarkable relationships with MEP amplitude and rMT. These results suggest that TMS-evoked neurophysiological parameters were useful measures for monitoring post-stroke patients.
Li, Xiao-Hong; Xu, Yu-Xin; Vance, Gill; Wang, Yun; Lv, Long-Bao; van Dam, Govert J.; Cao, Jian-Ping; Wilson, R. Alan
Background Rhesus macaques are unusual among schistosome hosts, self-curing from an established infection and thereafter manifesting solid immunity against a challenge, an ideal model for vaccine development. Previously, the immunological basis of self-cure was confirmed; surviving worms had ceased feeding but how immunological pressure achieved this was unclear. The schistosome esophagus is not simply a conduit for blood but plays a central role in its processing. Secretions from the anterior and posterior esophageal glands mix with incoming blood causing erythrocyte lysis and tethering and killing of leucocytes. Methodology/Principal Findings We have analysed the self-cure process in rhesus macaques infected with Schistosoma japonicum. Faecal egg output and circulating antigen levels were used to chart the establishment of a mature worm population and its subsequent demise. The physiological stress of surviving females at perfusion was especially evident from their pale, shrunken appearance, while changes in the structure and function of the esophagus were observed in both sexes. In the anterior region electron microscopy revealed that the vesicle secretory process was disrupted, the tips of lining corrugations being swollen by greatly enlarged vesicles and the putative sites of vesicle release obscured by intense deposits of IgG. The lumen of the posterior esophagus in starving worms was occluded by cellular debris and the lining cytoplasmic plates were closely adherent, also potentially preventing secretion. Seven proteins secreted by the posterior gland were identified and IgG responses were detected to some or all of them. Intrinsic rhesus IgG colocalized with secreted SjMEGs 4.1, 8.2, 9, 11 and VAL-7 on cryosections, suggesting they are potential targets for disruption of function. Conclusions/Significance Our data suggest that rhesus macaques self-cure by blocking esophagus function with antibody; the protein products of the glands provide a new class of
Hidecker, Mary Jo Cooley; Ho, Nhan Thi; Dodge, Nancy; Hurvitz, Edward A.; Slaughter, Jaime; Workinger, Marilyn Seif; Kent, Ray D.; Rosenbaum, Peter; Lenski, Madeleine; Messaros, Bridget M.; Vanderbeek, Suzette B.; Deroos, Steven; Paneth, Nigel
Aim: To investigate the relationships among the Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), and Communication Function Classification System (CFCS) in children with cerebral palsy (CP). Method: Using questionnaires describing each scale, mothers reported GMFCS, MACS, and CFCS levels in 222…
Harne, Swapnil; Pathak, Manish; Rattan, Kamal Nayan
Esophageal atresia with tracheoesophageal fistula (EA/TEF) associated with distal congenital esophageal stenosis (CES) is a well-known entity. We encountered three patients of EA/TEF associated with long and unusual CES. PMID:28083495
Nishibe, Mariko; Barbay, Scott; Guggenmos, David
Abstract We report the results of controlled cortical impact (CCI) centered on the caudal forelimb area (CFA) of rat motor cortex to determine the feasibility of examining cortical plasticity in a spared cortical motor area (rostral forelimb area, RFA). We compared the effects of three CCI parameter sets (groups CCI-1, CCI-2, and CCI-3) that differed in impactor surface shape, size, and location, on behavioral recovery and RFA structural and functional integrity. Forelimb deficits in the limb contralateral to the injury were evident in all three CCI groups assessed by skilled reach and footfault tasks that persisted throughout the 35-day post-CCI assessment period. Nissl-stained coronal sections revealed that the RFA was structurally intact. Intracortical microstimulation experiments conducted at 7 weeks post-CCI demonstrated that RFA was functionally viable. However, the size of the forelimb representation decreased significantly in CCI-1 compared to the control group. Subdivided into component movement categories, there was a significant group effect for proximal forelimb movements. The RFA area reduction and reorganization are discussed in relation to possible diaschisis, and to compensatory functional behavior, respectively. Also, an inverse correlation between the anterior extent of the lesion and the size of the RFA was identified and is discussed in relation to corticocortical connectivity. The results suggest that CCI can be applied to rat CFA while sparing RFA. This CCI model can contribute to our understanding of neural plasticity in premotor cortex as a substrate for functional motor recovery. PMID:20873958
Asai, Tomohisa; Sugimori, Eriko; Tanno, Yoshihiko
Atypical cerebral lateralization in motor and language functions in regard to schizotypal personality traits in healthy populations, as well as among schizophrenic patients, has attracted attention because these traits may represent a risk factor for schizophrenia. Although the relationship between handedness and schizotypal personality has been widely examined, few studies have adopted an experimental approach. This study consisted of three experiments focusing on motor and language functional lateralization in regard to schizotypal personality in the absence of mental illness: line-drawing, finger tapping, and a semantic go/no-go task. The results suggested that positive schizotypal personality might be related to functional non-lateralization in regard to at least some functions (e.g., spatial motor control and semantic processing in the present study). Subjects with high schizotypal personality traits performed equally with their right and left-hands in the line-drawing task and they reacted equally with their right and left-hands in a semantic go/no-go task involving semantic auditory stimuli presented in both ears. However, those low in schizotypal personality traits showed typical lateralization in response to these tasks. We discuss the implications of these findings for schizotypal atypical lateralization.
Bérard, C; Payan, C; Fermanian, J; Girardot, F
A new scale for motor function measurement has been developed for neuromuscular diseases. After the study of a preliminary and a first version, the validation study included 303 patients, aged 6 to 62 years. Seventy-two patients had Duchenne muscular dystrophy, 32 Becker muscular dystrophy, 30 limb-girdle muscular dystrophy, 39 facio-scapulo-humeral dystrophy, 29 myotonic dystrophy, 21 congenital myopathy, 10 congenital muscular dystrophy, 35 spinal muscular atrophy and 35 hereditary neuropathy. The sensitivity for change was evaluated with 152 patients one year after. The scale comprised 32 items, in three dimensions: standing position and transfers, axial and proximal motor function, distal motor function. High correlations (>0.80) were found between the total score and other scores: Vignos and Brooke grades, Functional Independence Measure, the global severity of disability evaluated with visual analog scales by physicians and physiotherapists. This scale is reliable, does not require any special equipment and is well accepted by patients. It takes an average of 36 min (range 8-75) to complete the scale. Preliminary results of the second evaluation showed good sensitivity to change since last visit, considering rating by patient, investigator or physiotherapist. Also, significant differences in scores are obtained with the greatest deterioration observed in Duchenne patients.
Duff, Susan V.; He, Jiaxiu; Nelsen, Monica A.; Lane, Christianne J.; Rowe, Veronica T.; Wolf, Steven L.; Dromerick, Alexander W.; Winstein, Carolee J.
Background One important objective for clinical trialists in rehabilitation is determining efficacy of interventions to enhance motor behavior. In part, limitation in the precision of measurement presents a challenge. The few valid, low-cost observational tools available to assess motor behavior cannot escape the variability inherent in test administration and scoring. This is especially true when there are multiple evaluators and raters as in the case of multi-site randomized controlled trials (RCT). One way to enhance reliability and reduce variability is to implement rigorous quality control (QC) procedures. Objective This paper describes a systematic QC process used to refine the administration and scoring procedures for the Wolf Motor Function Test (WMFT)-Functional Ability Scale (FAS). Methods The QC process, a systematic focus-group collaboration was developed and used for a phase III RCT, which enlisted multiple evaluators and an experienced WMFT-FAS Rater Panel. Results After three staged refinements to the administration and scoring instructions, we achieved a sufficiently high inter-rater reliability (weighted kappa = 0.8). Conclusions/Implications A systematic focus-group process was shown to be an effective method to improve reliability of observational assessment tools for motor behavior in neurorehabilitation. A reduction in noise-related variability in performance assessments will increase power and potentially lower the number needed to treat. Improved precision of measurement can lead to more cost effective and efficient clinical trials. Finally, we suggest that improved precision in measures of motor behavior may provide more insight into recovery mechanisms than a single measure of movement time alone. PMID:25323459
Kloppel, Stefan; Draganski, Bogdan; Siebner, Hartwig R.; Tabrizi, Sarah J.; Weiller, Cornelius; Frackowiak, Richard S. J.
Involuntary choreiform movements are a clinical hallmark of Huntington's disease. Studies in clinically affected patients suggest a shift of motor activations to parietal cortices in response to progressive neurodegeneration. Here, we studied pre-symptomatic gene carriers to examine the compensatory mechanisms that underlie the phenomenon of…
Wittenberg, George F.; Richards, Lorie G.; Jones-Lush, Lauren M.; Roys, Steven R.; Gullapalli, Rao P.; Yang, Suzy; Guarino, Peter D.; Lo, Albert C.
Background and Purpose: The brain changes that underlie therapy-induced improvement in motor function after stroke remain obscure. This study sought to demonstrate the feasibility and utility of measuring motor system physiology in a clinical trial of intensive upper extremity rehabilitation in chronic stroke-related hemiparesis. Methods: This was a substudy of two multi-center clinical trials of intensive robotic and intensive conventional therapy arm therapy in chronic, significantly hemiparetic, stroke patients. Transcranial magnetic stimulation was used to measure motor cortical output to the biceps and extensor digitorum communus muscles. Magnetic resonance imaging (MRI) was used to determine the cortical anatomy, as well as to measure fractional anisotropy, and blood oxygenation (BOLD) during an eyes-closed rest state. Region-of-interest time-series correlation analysis was performed on the BOLD signal to determine interregional connectivity. Functional status was measured with the upper extremity Fugl-Meyer and Wolf Motor Function Test. Results: Motor evoked potential (MEP) presence was associated with better functional outcomes, but the effect was not significant when considering baseline impairment. Affected side internal capsule fractional anisotropy was associated with better function at baseline. Affected side primary motor cortex (M1) activity became more correlated with other frontal motor regions after treatment. Resting state connectivity between affected hemisphere M1 and dorsal premotor area (PMAd) predicted recovery. Conclusions: Presence of motor evoked potentials in the affected motor cortex and its functional connectivity with PMAd may be useful in predicting recovery. Functional connectivity in the motor network shows a trends towards increasing after intensive robotic or non-robotic arm therapy. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00372411 \\& NCT00333983. PMID:28357039
Morita, Yoshifumi; Hirose, Akinori; Uno, Takashi; Uchid, Masaki; Ukai, Hiroyuki; Matsui, Nobuyuki
In this paper we propose a new rehabilitation training support system for upper limbs. The proposed system enables therapists to quantitatively evaluate the therapeutic effect of upper limb motor function during training, to easily change the load of resistance of training and to easily develop a new training program suitable for the subjects. For this purpose we develop control algorithms of training programs in the 3D force display robot. The 3D force display robot has parallel link mechanism with three motors. The control algorithm simulating sanding training is developed for the 3D force display robot. Moreover the teaching/training function algorithm is developed. It enables the therapists to easily make training trajectory suitable for subject's condition. The effectiveness of the developed control algorithms is verified by experiments.
Huttenlocher, Stefan; Sehmisch, Lena; Rudat, Volker; Rades, Dirk
The major goal of this study was the identification of predictors for motor function and survival after irradiation alone for metastatic epidural spinal cord compression (MESCC) from melanoma. Ten variables (age, gender, performance status, number of involved vertebrae, pre-radiotherapy ambulatory status, further bone metastases, visceral metastases, interval from melanoma diagnosis to MESCC, time developing motor deficits before radiotherapy, fractionation regimen) were investigated for post-radiotherapy motor function, ambulatory status and survival in 27 patients. On multivariate analysis, motor function was significantly associated with time developing motor deficits (P = 0.006). On univariate analysis, post-radiotherapy ambulatory rates were associated with pre-radiotherapy ambulatory status (P < 0.001) and performance status (P = 0.046). Variables having a significant impact on survival in the univariate analysis were performance status (P < 0.001), number of involved vertebrae (P = 0.007), pre-radiotherapy ambulatory status (P = 0.020), further bone metastases (P = 0.023), visceral metastases (P < 0.001), and time developing motor deficits (P = 0.038). On multivariate analysis of survival, the Eastern Cooperative Oncology Group (ECOG) performance status (risk ratio [RR] = 4.35; 95% confidence interval [CI] = 1.04-16.67; P = 0.044) and visceral metastases (RR = 3.70; 95% CI = 1.10-12.50; P = 0.034) remained significant and were included in a survival score. Scoring points were obtained from 6-month survival rates divided by 10. Total scores represented the sum scores of both variables and were 3, 9 or 15 points. Six-month survival rates were 7%, 29% and 100% (P = 0.004). Thus, three predictors for functional outcomes were identified. The newly developed survival score included three prognostic groups. Patients with 3 points may receive 1 × 8 Gy, patients with 9 points 5 × 4 Gy and patients achieving 15 points longer
Ho, Shih-Chi; Chang, Chi-Sen; Wu, Chun-Ying; Chen, Gran-Hum
The relationship between esophageal motor abnormalities and GERD has been widely studied. The purpose of this study was to identify the prevalence of ineffective esophageal motility (IEM) in patients with GERD. In addition, we also evaluated esophageal acid exposure, acid clearance, and endoscopic esophagitis in GERD patients with IEM. Of 89 patients enrolled in this study, 47 (52.8%) were found to have nonspecific esophageal motility disorder (NEMD). Forty-four of the 47 (93.6%) patients with NEMD met the diagnostic criteria for IEM. The overall incidence of IEM in GERD patients was 49.4%. Patients with IEM had significant increases in upright and recumbent mean fraction of time pH < 4 (6.70% and 4.38%) and mean recumbent esophageal acid clearance (12.45 min/reflux) when compared to those with other motility findings. Seventeen of the 44 (39%) IEM patients did not have endoscopic esophagitis. On the other hand, 26 of the 39 (67%) patients with normal manometry had endoscopic esophagitis. We concluded that not only is the prevalence of IEM high in GERD, but also that IEM patients have more recumbent gastroesophageal reflux and delayed acid clearance. Combined with endoscopic findings, we propose that IEM can be viewed as a specific entity of primary esophageal motility disorder in patients with GERD.
Takamatsu, Yasuyuki; Tamakoshi, Keigo; Waseda, Yuya; Ishida, Kazuto
Rehabilitative approaches benefit motor functional recovery after stroke and relate to neuronal plasticity. We investigated the effects of a treadmill running exercise on the motor functional recovery and neuronal plasticity after collagenase-induced striatal intracerebral hemorrhage (ICH) in rats. Male Wistar rats were injected with type IV collagenase into the left striatum to induce ICH. Sham-operated animals were injected with saline instead of collagenase. The animals were randomly assigned to the sham control (SC), the sham exercise (SE), the ICH control (IC), or the ICH exercise (IE) group. The exercise groups were forced to run on a treadmill at a speed of 9 m/min for 30 min/day between days 4 and 14 after surgery. Behavioral tests were performed using a motor deficit score, a beam-walking test and a cylinder test. At fifteen days after surgery, the animals were sacrificed, and their brains were removed. The motor function of the IE group significantly improved compared with the motor function of the IC group. No significant differences in cortical thickness were found between the groups. The IC group had fewer branches and shorter dendrite lengths compared with the sham groups. However, dendritic branches and lengths were not significantly different between the IE and the other groups. Tropomyosin-related kinase B (TrkB) expression levels increased in the IE compared with IC group, but no significant differences in other protein (brain-derived neurotrophic factor, BDNF; Nogo-A; Rho-A/Rho-associated protein kinase 2, ROCK2) expression levels were found between the groups. These results suggest that improved motor function after a treadmill running exercise after ICH may be related to the prevention of dendritic regression due to TrkB upregulation.
Cardinali, L; Brozzoli, C; Finos, L; Roy, A C; Farnè, A
Previous studies showed that using tools modifies the agent's body and space representation. However, it is still not clear which rules govern those remapping processes. Here, we studied the differential role played by the morpho-functional characteristics of a tool and the sensori-motor constraints that a tool imposes on the hand. To do so, we asked a group of participants to reach and grasp an object using, in different conditions, two different tools: Pliers, to be acted upon by the index and thumb fingertips, and Sticks, taped to the same two digits. The two tools were equivalent in terms of morpho-functional characteristics, providing index finger and thumb with the same amount of elongation. Crucially, however, they imposed different sensori-motor constraints on the acting fingers. We measured and compared the kinematic profile of free-hand movements performed before and after the use of both devices. As predicted on the basis of their equivalent morpho-functional characteristics, both tools induced similar changes in the fingers (but not the arm) kinematics compatible with the hand being represented as bigger. Furthermore, the different sensori-motor constraints imposed by Pliers and Sticks over the hand, induced differential updates of the hand representation. In particular, the Sticks selectively affected the kinematics of the two fingers they were taped on, whereas Pliers had a more global effect, affecting the kinematics of hand movements not performed during the use of the tool. These results suggest that tool-use induces a rapid update of the hand representation in the brain, not only on the basis of the morpho-functional characteristics of the tool, but also depending on the specific sensori-motor constraints imposed by the tool.
Oshima, Yasushi; Fetto, Joseph F
The low incidence of intraneural ganglion makes it difficult to diagnose and treat before it becomes serious nerve damage. This case describes a 69-year-old female, who suffered from the right drop foot and was diagnosed as a peroneal intraneural ganglion. Resection of the mass relieved the pain; however, motor function was not recovered. Early diagnosis and nerve decompression are essential for the peroneal intraneural ganglion before critical nerve symptoms.
Kou, Wenjun; Bhalla, Amneet Pal Singh; Griffith, Boyce E.; Pandolfino, John E.; Kahrilas, Peter J.; Patankar, Neelesh A.
Esophageal transport is a physiological process that mechanically transports an ingested food bolus from the pharynx to the stomach via the esophagus, a multilayered muscular tube. This process involves interactions between the bolus, the esophagus, and the neurally coordinated activation of the esophageal muscles. In this work, we use an immersed boundary (IB) approach to simulate peristaltic transport in the esophagus. The bolus is treated as a viscous fluid that is actively transported by the muscular esophagus, and the esophagus is modeled as an actively contracting, fiber-reinforced tube. Before considering the full model of the esophagus, however, we first consider a standard benchmark problem of flow past a cylinder. Next a simplified version of our model is verified by comparison to an analytic solution to the tube dilation problem. Finally, three different complex models of the multi-layered esophagus, which differ in their activation patterns and the layouts of the mucosal layers, are extensively tested. To our knowledge, these simulations are the first of their kind to incorporate the bolus, the multi-layered esophagus tube, and muscle activation into an integrated model. Consistent with experimental observations, our simulations capture the pressure peak generated by the muscle activation pulse that travels along the bolus tail. These fully resolved simulations provide new insights into roles of the mucosal layers during bolus transport. In addition, the information on pressure and the kinematics of the esophageal wall resulting from the coordination of muscle activation is provided, which may help relate clinical data from manometry and ultrasound images to the underlying esophageal motor function. PMID:26190859
Kou, Wenjun; Bhalla, Amneet Pal Singh; Griffith, Boyce E.; Pandolfino, John E.; Kahrilas, Peter J.; Patankar, Neelesh A.
Esophageal transport is a physiological process that mechanically transports an ingested food bolus from the pharynx to the stomach via the esophagus, a multi-layered muscular tube. This process involves interactions between the bolus, the esophagus, and the neurally coordinated activation of the esophageal muscles. In this work, we use an immersed boundary (IB) approach to simulate peristaltic transport in the esophagus. The bolus is treated as a viscous fluid that is actively transported by the muscular esophagus, and the esophagus is modeled as an actively contracting, fiber-reinforced tube. Before considering the full model of the esophagus, however, we first consider a standard benchmark problem of flow past a cylinder. Next a simplified version of our model is verified by comparison to an analytic solution to the tube dilation problem. Finally, three different complex models of the multi-layered esophagus, which differ in their activation patterns and the layouts of the mucosal layers, are extensively tested. To our knowledge, these simulations are the first of their kind to incorporate the bolus, the multi-layered esophagus tube, and muscle activation into an integrated model. Consistent with experimental observations, our simulations capture the pressure peak generated by the muscle activation pulse that travels along the bolus tail. These fully resolved simulations provide new insights into roles of the mucosal layers during bolus transport. In addition, the information on pressure and the kinematics of the esophageal wall resulting from the coordination of muscle activation is provided, which may help relate clinical data from manometry and ultrasound images to the underlying esophageal motor function.
Kou, Wenjun; Bhalla, Amneet Pal Singh; Griffith, Boyce E; Pandolfino, John E; Kahrilas, Peter J; Patankar, Neelesh A
Esophageal transport is a physiological process that mechanically transports an ingested food bolus from the pharynx to the stomach via the esophagus, a multilayered muscular tube. This process involves interactions between the bolus, the esophagus, and the neurally coordinated activation of the esophageal muscles. In this work, we use an immersed boundary (IB) approach to simulate peristaltic transport in the esophagus. The bolus is treated as a viscous fluid that is actively transported by the muscular esophagus, and the esophagus is modeled as an actively contracting, fiber-reinforced tube. Before considering the full model of the esophagus, however, we first consider a standard benchmark problem of flow past a cylinder. Next a simplified version of our model is verified by comparison to an analytic solution to the tube dilation problem. Finally, three different complex models of the multi-layered esophagus, which differ in their activation patterns and the layouts of the mucosal layers, are extensively tested. To our knowledge, these simulations are the first of their kind to incorporate the bolus, the multi-layered esophagus tube, and muscle activation into an integrated model. Consistent with experimental observations, our simulations capture the pressure peak generated by the muscle activation pulse that travels along the bolus tail. These fully resolved simulations provide new insights into roles of the mucosal layers during bolus transport. In addition, the information on pressure and the kinematics of the esophageal wall resulting from the coordination of muscle activation is provided, which may help relate clinical data from manometry and ultrasound images to the underlying esophageal motor function.
Otero, Maria G; Alloatti, Matías; Cromberg, Lucas E; Almenar-Queralt, Angels; Encalada, Sandra E; Pozo Devoto, Victorio M; Bruno, Luciana; Goldstein, Lawrence S B; Falzone, Tomás L
Protein degradation by the ubiquitin-proteasome system in neurons depends on the correct delivery of the proteasome complex. In neurodegenerative diseases, aggregation and accumulation of proteins in axons link transport defects with degradation impairments; however, the transport properties of proteasomes remain unknown. Here, using in vivo experiments, we reveal the fast anterograde transport of assembled and functional 26S proteasome complexes. A high-resolution tracking system to follow fluorescent proteasomes revealed three types of motion: actively driven proteasome axonal transport, diffusive behavior in a viscoelastic axonema and proteasome-confined motion. We show that active proteasome transport depends on motor function because knockdown of the KIF5B motor subunit resulted in impairment of the anterograde proteasome flux and the density of segmental velocities. Finally, we reveal that neuronal proteasomes interact with intracellular membranes and identify the coordinated transport of fluorescent proteasomes with synaptic precursor vesicles, Golgi-derived vesicles, lysosomes and mitochondria. Taken together, our results reveal fast axonal transport as a new mechanism of proteasome delivery that depends on membrane cargo 'hitch-hiking' and the function of molecular motors. We further hypothesize that defects in proteasome transport could promote abnormal protein clearance in neurodegenerative diseases.
Araki, Toshihiko; Hirata, Masayuki; Sugata, Hisato; Yanagisawa, Takufumi; Onishi, Mai; Watanabe, Yoshiyuki; Omura, Kayoko; Honda, Chika; Hayakawa, Kazuo; Yorifuji, Shiro
To investigate the effect of genetic and environmental influences on cerebral motor function, we determined similarities and differences of movement-related cortical fields (MRCFs) in middle-aged and elderly monozygotic (MZ) twins. MRCFs were measured using a 160-channel magnetoencephalogram system when MZ twins were instructed to repeat lifting of the right index finger. We compared latency, amplitude, dipole location, and dipole intensity of movement-evoked field 1 (MEF1) between 16 MZ twins and 16 pairs of genetically unrelated pairs. Differences in latency and dipole location between MZ twins were significantly less than those between unrelated age-matched pairs. However, amplitude and dipole intensity were not significantly different. These results suggest that the latency and dipole location of MEF1 are determined early in life by genetic and early common environmental factors, whereas amplitude and dipole intensity are influenced by long-term environmental factors. Improved understanding of genetic and environmental factors that influence cerebral motor function may contribute to evaluation and improvement for individual motor function. PMID:24994981
Dombeck, Daniel A.; Graziano, Michael S.; Tank, David W.
Macroscopic (millimeter scale) functional clustering is a hallmark characteristic of motor cortex spatial organization in awake behaving mammals; however, almost no information is known about the functional micro-organization (~100 microns scale). Here, we optically recorded intracellular calcium transients of layer 2/3 neurons with cellular resolution over ~200 micron diameter fields in the forelimb motor cortex of mobile, head-restrained mice during two distinct movements (running and grooming). We showed that the temporal correlation between neurons was statistically larger the closer the neurons were to each other. We further explored this correlation by using two separate methods to spatially segment the neurons within each imaging field: K-means clustering and correlations between single neuron activity and mouse movements. The two methods segmented the neurons similarly and led to the conclusion that the origin of the inverse relationship between correlation and distance seen statistically was two-fold: clusters of highly temporally correlated neurons were often spatially distinct from one another and (even when the clusters were spatially intermingled) within the clusters, the more correlated the neurons were to each other, the shorter the distance between them. Our results represent a direct observation of functional clustering within the micro-circuitry of the awake mouse motor cortex. PMID:19889987
Huang, Bo-Tsang; Chang, Pu-Yuan; Su, Ching-Hua; Chao, Chuck C.-K.; Lin-Chao, Sue
Background Growth arrest-specific gene 7 (Gas7) has previously been shown to be involved in neurite outgrowth in vitro; however, its actual role has yet to be determined. To investigate the physiological function of Gas7 in vivo, here we generated a Gas7-deficient mouse strain with a labile Gas7 mutant protein whose functions are similar to wild-type Gas7. Methodology/Principal Findings Our data show that aged Gas7-deficient mice have motor activity defects due to decreases in the number of spinal motor neurons and in muscle strength, of which the latter may be caused by changes in muscle fiber composition as shown in the soleus. In cross sections of the soleus of Gas7-deficient mice, gross morphological features and levels of myosin heavy chain I (MHC I) and MHC II markers revealed significantly fewer fast fibers. In addition, we found that nerve terminal sprouting, which may be associated with slow and fast muscle fiber composition, was considerably reduced at neuromuscular junctions (NMJ) during aging. Conclusions/Significance These findings indicate that Gas7 is involved in motor neuron function associated with muscle strength maintenance. PMID:22662195
Oskoui, Maryam; Majnemer, Annette; Dagenais, Lynn; Shevell, Michael I
A retrospective cohort study was conducted to describe the relationship between gross motor function and manual ability in children with cerebral palsy and explore differences between cerebral palsy subtypes and associated comorbidities. Children with cerebral palsy born between 1999 and 2008 were included from the Registre de la Paralyse Cérébrale de Québec identifying 332 children. The overall agreement between Gross Motor Function Classification System and Manual Ability Classification Scale Levels was moderate (kappa 0.457, standard error 0.034) with a strong positive correlation (Spearman rho of 0.820, standard error 0.023). This agreement was moderate among children with spastic quadriparesis and dysketic cerebral palsy, fair in children with spastic diplegia, and poor in children with spastic hemiplegia. Children with cognitive impairment showed a higher correlation than those without cognitive impairment. The correlation between gross motor function and manual ability in children with CP varies based on neurologic subtype and cognitive level.
Varga, Gábor; Bálint, András; Burghardt, Beáta; D'Amato, Massimo
Cholecystokinin (CCK) is a brain-gut peptide; it functions both as a neuropeptide and as a gut hormone. Although the pancreas and the gallbladder were long thought to be the principal peripheral targets of CCK, CCK receptors are found throughout the gut. It is likely that CCK has a physiological role not only in the stimulation of pancreatic and biliary secretions but also in the regulation of gastrointestinal motility. The motor effects of CCK include postprandial inhibition of gastric emptying and inhibition of colonic transit. It is now evident that at least two different receptors, CCK1 and CCK2 (formerly CCK-A and CCK-B, respectively), mediate the actions of CCK. Both localization and functional studies suggest that the motor effects of CCK are mediated by CCK1 receptors in humans. Since CCK is involved in sensory and motor responses to distension in the intestinal tract, it may contribute to the symptoms of constipation, bloating and abdominal pain that are often characteristic of functional gastrointestinal disorders in general and irritable bowel syndrome (IBS), in particular. CCK1 receptor antagonists are therefore currently under development for the treatment of constipation-predominant IBS. Clinical studies suggest that CCK1 receptor antagonists are effective facilitators of gastric emptying and inhibitors of gallbladder contraction and can accelerate colonic transit time in healthy volunteers and patients with IBS. These drugs are therefore potentially of great value in the treatment of motility disorders such as constipation and constipation-predominant IBS. PMID:15100163
Chris Ajonijebu, Duyilemi; Adeyemi Adeniyi, Philip; Oloruntoba Adekeye, Adeshina; Peter Olatunji, Babawale; Olakunle Ishola, Azeez; Michael Ogundele, Olalekan
In this study we evaluated the time dependence in cadmium-nicotine interaction and its effect on motor function, anxiety linked behavioural changes, serum electrolytes, and weight after acute and chronic treatment in adult male mice. Animals were separated randomly into four groups of n = 6 animals each. Treatment was done with nicotine, cadmium, or nicotine-cadmium for 21 days. A fourth group received normal saline for the same duration (control). Average weight was determined at 7-day interval for the acute (D1-D7) and chronic (D7-D21) treatment phases. Similarly, the behavioural tests for exploratory motor function (open field test) and anxiety were evaluated. Serum electrolytes were measured after the chronic phase. Nicotine, cadmium, and nicotine-cadmium treatments caused no significant change in body weight after the acute phase while cadmium-nicotine and cadmium caused a decline in weight after the chronic phase. This suggests the role of cadmium in the weight loss observed in tobacco smoke users. Both nicotine and cadmium raised serum Ca2+ concentration and had no significant effect on K+ ion when compared with the control. In addition, nicotine-cadmium treatment increased bioaccumulation of Cd2+ in the serum which corresponded to a decrease in body weight, motor function, and an increase in anxiety. PMID:26317007
Holschneider, D P; Maarek, J-M I
Brain mapping in the freely moving animal is useful for studying motor circuits, not only because it avoids the potential confound of sedation or restraints, but because activated brain states may serve to accentuate differences that only manifest partially while a subject is in the resting state. Perfusion or metabolic mapping using autoradiography allows one to examine changes in brain function at the circuit level across the entire brain with a spatial resolution (approximately 100 micro) appropriate for the rat or mouse brain, and a temporal resolution (seconds-minutes) sufficient for capturing acute brain changes. Here we summarize the application of these methods to the functional brain mapping of behaviors involving locomotion of small animals, methods for the three-dimensional reconstruction of the brain from autoradiographic sections, voxel based analysis of the whole brain, and generation of maps of the flattened rat cortex. Application of these methods in animal models promises utility in improving our understanding of motor function in the normal brain, and of the effects of neuropathology and treatment interventions such as exercise have on the reorganization of motor circuits.
Quandt, Fanny; Hummel, Friedhelm C
Neuromuscular stimulation has been used as one potential rehabilitative treatment option to restore motor function and improve recovery in patients with paresis. Especially stroke patients who often regain only limited hand function would greatly benefit from a therapy that enhances recovery and restores movement. Multiple studies investigated the effect of functional electrical stimulation on hand paresis, the results however are inconsistent. Here we review the current literature on functional electrical stimulation on hand motor recovery in stroke patients. We discuss the impact of different parameters such as stage after stoke, degree of impairment, spasticity and treatment protocols on the functional outcome. Importantly, we outline the results from recent studies investigating the cortical effects elicited by functional electrical stimulation giving insights into the underlying mechanisms responsible for long-term treatment effects. Bringing together the findings from present research it becomes clear that both, treatment outcomes as well as the neurophysiologic mechanisms causing functional recovery, vary depending on patient characteristics. In order to develop unified treatment guidelines it is essential to conduct homogenous studies assessing the impact of different parameters on rehabilitative success.
Patel, Ashish; Suntharalingam, Mohan
Radiotherapy and surgery have both played prominent roles in the treatment of esophageal cancer since the beginning of the 20th century. Although the use of radiotherapy alone to treat esophageal cancer has a long history, it has not demonstrated improved outcomes compared with surgery alone. The disappointing rates of survival and local control associated with single-modality therapy and the need for effective nonsurgical management led to the development of definitive chemoradiotherapy paradigms for esophageal cancer. Adding cytotoxic chemotherapy to radiotherapy for additive or synergistic effect was described as early as 1968, and over time, treatment has shifted from single-modality therapy toward combined-modality therapy using chemotherapy and radiotherapy. This approach eventually demonstrated superior outcomes in patients with esophageal cancer when compared to radiotherapy alone. Maximum benefit of this therapy depends on the appropriate addition of surgery and the optimization of radiosensitizing chemotherapy. A burgeoning area of research has focused on improving definitive chemoradiotherapy strategies through the incorporation of newer chemotherapeutic agents and targeted biologic agents. An overview of the history of chemoradiotherapy in the treatment of esophageal cancer is presented, as well as a discussion of ongoing studies and future areas of promising research. PMID:19461907
Kozak, Katarzyna; Rębowski, Marek; Kozak, Józef
Introduction Intramural esophageal tumors (IET) are located between unchanged mucous membrane and muscularis mucosae. They can be both benign and malignant. Aim To evaluate diagnostic and therapeutic difficulties of IET. Material and methods During the years 2010–2015, 11 patients with IET were treated in our clinic. Diagnostics included gastroscopy, computed tomography of the chest, endoscopic ultrasound (EUS) guided fine needle biopsy, and positron emission tomography (PET) of the esophagus in cases with no histopathological confirmation. Results Based on the conducted analysis we diagnosed 1 case of gastrointestinal stromal tumor (GIST), 1 case of adenocarcinoma, and 2 cases of esophageal cysts. In another 7 cases radiological images resembled leiomyoma but with no histopathological confirmation. Esophagectomy was performed in 2 cases of malignant tumors and 1 case of a large benign tumor. In other cases surgical enucleation of tumors was performed. Postoperatively we diagnosed 6 cases of leiomyoma, 1 case of schwannoma, 2 esophageal cysts, 1 case of GIST and 1 of esophageal cancer. Conclusions Intramural esophageal tumors is a very diverse group of tumors, both malignant and benign. In every case of IET we should seek histopathological conformation. Treatment of IET depends on localization, size and histopathological type of lesion. PMID:28096828
Forbes, Ashley; Cooze, Jared; Malone, Craig; French, Vanessa; Weber, John T
Ethanol has well described acute effects on motor function, and chronic alcoholism can damage the cerebellum, which is associated with motor coordination, as well as motor learning. Binge drinking is common among preadolescents and adolescents, and this type of ethanol exposure may lead to long-term nervous system damage. In the current study, we analyzed the effects of periadolsecent/adolescent ethanol exposure on motor function in both male and female Sprague-Dawley rats. To simulate binge drinking, animals received an intraperitoneal injection of 25% (v/v) ethanol (3 g/kg) on postnatal days (PND) 25, 26, 29, 30, 33, 34, 37 and 38. On PND 42 and PND 61 animals were tested on their ability to traverse both square and round beams. There were no significant differences in the time to traverse the beams, or the amount of foot slips, between treated and untreated animals. On PND 48 and PND 62, animals were tested using a horizontal ladder walking apparatus. On PND 48 there were no differences in the ability of treated and untreated animals to traverse the ladder. On PND 62, there were no differences in the time to traverse the ladder, but ethanol treated animals had more foot slips than controls. On PND 43, we conducted footprint analysis of control and treated animals, which included measurements of stride length, paw overlap, and angle of foot placement. There was a significant difference in the angle of foot placement between treated and control animals, and this finding was significant for both male and female animals. There was also a significant overall difference in paw overlap between treatment groups. Although this effect was manifested in male animals there was no significant difference in females. These findings suggest that adolescent ethanol exposure can produce long-lasting effects on motor coordination, and that overall, effects are similar in males and females. In a second set of experiments, male rats received i.p. ethanol (3 g/kg) for 7 days (P31
Capaday, Charles; Ethier, Christian; Van Vreeswijk, Carl; Darling, Warren G.
Recent studies on the functional organization and operational principles of the motor cortex (MCx), taken together, strongly support the notion that the MCx controls the muscle synergies subserving movements in an integrated manner. For example, during pointing the shoulder, elbow and wrist muscles appear to be controlled as a coupled functional system, rather than singly and separately. The recurrent pattern of intrinsic synaptic connections between motor cortical points is likely part of the explanation for this operational principle. So too is the reduplicated, non-contiguous and intermingled representation of muscles in the MCx. A key question addressed in this article is whether the selection of movement related muscle synergies is a dynamic process involving the moment to moment functional linking of a variety of motor cortical points, or rather the selection of fixed patterns embedded in the MCx circuitry. It will be suggested that both operational principles are probably involved. We also discuss the neural mechanisms by which cortical points may be dynamically linked to synthesize movement related muscle synergies. Separate corticospinal outputs sum linearly and lead to a blending of the movements evoked by activation of each point on its own. This operational principle may simplify the synthesis of motor commands. We will discuss two possible mechanisms that may explain linear summation of outputs. We have observed that the final posture of the arm when pointing to a given spatial location is relatively independent of its starting posture. From this observation and the recurrent nature of the MCx intrinsic connectivity we hypothesize that the basic mode of operation of the MCx is to associate spatial location to final arm posture. We explain how the recurrent network connectivity operates to generate the muscle activation patterns (synergies) required to move the arm and hold it in its final position. PMID:23616749
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.
Afonin, B V; Rogov, V A; Ruvinova, L G; Poliakov, B I; Inozemtsev, S L
The effect of three exposures to Coriolis acceleration on the frequency and amplitude of fasting stomach contractions was investigated in 6 resistant and 16 susceptible to motion sickness test subjects. After tests all of them underwent gastroduodenoscopy and 4 subjects from each group were subjected to echography to measure gall bladder contractility in response to glucose-milk loads. After tests the motor activity of the stomach increased slightly in resistant subjects due to an increase of the amplitude and a slight decrease of biopotential frequency. During gastroscopy antral and pyloric sphincters were closed. In the stomach there was an insignificant amount of contents without gall. In the susceptible group, the motor activity was, on the contrary, inhibited due to a significant decline of the wave amplitude and frequency (by 40% and 11%, respectively). In the stomach, one or both sphincters were widely open; it also contained a large amount of gastric juice and gall. In 36% of susceptible and 17% resistant subjects, diaphragmatic hernia (at the esophageal opening) was found. Ultrasonic examination of the gall bladder showed that susceptible subjects developed its faster and stronger contraction when compared to resistant subject in response to glucose-milk loading. This pointed to a more prolonged duration of the gall excretion phase. Reactive changes of the gastroduodenal zone in response to motion tests facilitated duodenal-gastric reflux and major gastrointestinal symptoms of motion sickness.
Park, Jaechan; Cho, Jin Whan; Youn, Jinyoung; Kim, Yun Kwan; Kim, Sun Woong; Kim, Yun-Hee
Objective To investigate the clinical significance of upper and lower extremity transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs) in patients with parkinsonism. Methods Twenty patients (14 men, 6 women; mean age 70.5±9.1 years) suffering from parkinsonism were included in this study. All participants underwent single-pulse TMS session to assess the corticospinal excitability of the upper and lower extremity motor cortex. The resting motor threshold (RMT) was defined as the lowest stimulus intensity able to evoke MEPs of an at least 50 µV peak-to-peak amplitude in 5 of 10 consecutive trials. Five sweeps of MEPs at 120% of the RMT were performed, and the mean amplitude and latency of the MEPs were calculated. Patients were also assessed using the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) and the 5-meter Timed Up and Go (5m-TUG) test. Results There was a significant positive correlation between the RMTs of MEPs in the upper and lower extremities (r=0.612, p=0.004) and between the amplitude of MEPs in the upper and lower extremities (r=0.579, p=0.007). The RMT of upper extremity MEPs showed a significant negative relationship with the UPDRS-III score (r=–0.516, p=0.020). In addition, RMTs of lower extremity MEPs exhibited a negative relationship with the UPDRS-III score, but the association was not statistically significant (r=–406, p=0.075). Conclusion These results indicated that the RMT of MEPs reflect the severity of motor dysfunction in patients with parkinsonism. MEP is a potential quantitative, electrodiagnostic method to assess motor function in patients with parkinsonism. PMID:26949673
Nakamura, T; Ghilardi, M F; Mentis, M; Dhawan, V; Fukuda, M; Hacking, A; Moeller, J R; Ghez, C; Eidelberg, D
We examined the neural circuitry underlying the explicit learning of motor sequences in normal subjects and patients with early stage Parkinson's disease (PD) using 15O-water (H2 15O) positron emission tomography (PET) and network analysis. All subjects were scanned while learning motor sequences in a task emphasizing explicit learning, and during a kinematically controlled motor execution reference task. Because different brain networks are thought to subserve target acquisition and retrieval during motor sequence learning, we used separate behavioral indices to quantify these aspects of learning during the PET experiments. In the normal cohort, network analysis of the PET data revealed a significant covariance pattern associated with acquisition performance. This topography was characterized by activations in the left dorsolateral prefrontal cortex (PFdl), rostral supplementary motor area (preSMA), anterior cingulate cortex, and in the left caudate/putamen. A second independent covariance pattern was associated with retrieval performance. This topography was characterized by bilateral activations in the premotor cortex (PMC), and in the right precuneus and posterior parietal cortex. The normal learning-related topographies failed to predict acquisition performance in PD patients and predicted retrieval performance less accurately in the controls. A separate network analysis was performed to identify discrete learning-related topographies in the PD cohort. In PD patients, acquisition performance was associated with a covariance pattern characterized by activations in the left PFdl, ventral prefrontal, and rostral premotor regions, but not in the striatum. Retrieval performance in PD patients was associated with a covariance pattern characterized by activations in the right PFdl, and bilaterally in the PMC, posterior parietal cortex, and precuneus. These results suggest that in early stage PD sequence learning networks are associated with additional cortical
Shah, A K; Wolfsen, H C; Hemminger, L L; Shah, A A; DeVault, K R
Esophageal dysmotility is common in patients with Barrett's esophagus. Previously we have reported deterioration of esophageal motility after photodynamic therapy (PDT) in a heterogeneous group of patients with esophageal carcinoma. This prospective study in consecutive patients describes changes in motility noted after endoscopic ablation. Forty-seven patients referred to our institution for endoscopic ablation for Barrett's high grade dysplasia or mucosal carcinoma between August 2001 and May 2003 were prospectively evaluated with esophageal manometry before and after porfimer sodium PDT. Six patients did not complete the study. Manometry results were classified as normal, diffuse esophageal spasm, ineffective esophageal motility, or aperistalsis. Abnormal esophageal motility was found in 14 of 47 (30%) patients at study entry ([diffuse esophageal spasm] DES-3, [ineffective esophageal motility] IEM-7, Aperistalsis-4). After PDT, 11 of 41 patients with paired studies experienced a change in manometric diagnosis. Three patients had an improvement in motility, seven a worsening and one changed diagnosis, but did not particularly worsen or improve. No patient developed new aperistalsis. Therefore, abnormal motility was present in 19 of 41 (46%) patients after PDT (DES-2, IEM-14, Aperistalsis-3). There was a statistically significant (P = 0.016) relationship with longer segment Barrett's esophagus and deterioration of function. Baseline abnormalities in motility can occur in patients with Barrett's high-grade dysplasia or mucosal carcinoma. Changes in esophageal function also may occur following photodynamic therapy, but usually are not clinically significant. Worsening in function was more likely to occur in patients with longer segment Barrett's esophagus.
Mulavara, Ajitkumar P; Feiveson, Alan H; Fiedler, James; Cohen, Helen; Peters, Brian T; Miller, Chris; Brady, Rachel; Bloomberg, Jacob J
Astronauts returning from space flight and performing Earth-bound activities must rapidly transition from the microgravity-adapted sensorimotor state to that of Earth's gravity. The goal of the current study was to assess locomotor dysfunction and recovery of function after long-duration space flight using a test of functional mobility. Eighteen International Space Station crewmembers experiencing an average flight duration of 185 days performed the functional mobility test (FMT) pre-flight and post-flight. To perform the FMT, subjects walked at a self selected pace through an obstacle course consisting of several pylons and obstacles set up on a base of 10-cm-thick, medium-density foam for a total of six trials per test session. The primary outcome measure was the time to complete the course (TCC, in seconds). To assess the long-term recovery trend of locomotor function after return from space flight, a multilevel exponential recovery model was fitted to the log-transformed TCC data. All crewmembers exhibited altered locomotor function after space flight, with a median 48% increase in the TCC. From the fitted model we calculated that a typical subject would recover to 95% of his/her pre-flight level at approximately 15 days post-flight. In addition, to assess the early motor learning responses after returning from space flight, we modeled performance over the six trials during the first post-flight session by a similar multilevel exponential relation. We found a significant positive correlation between measures of long-term recovery and early motor learning (P < 0.001) obtained from the respective models. We concluded that two types of recovery processes influence an astronaut's ability to re-adapt to Earth's gravity environment. Early motor learning helps astronauts make rapid modifications in their motor control strategies during the first hours after landing. Further, this early motor learning appears to reinforce the adaptive realignment, facilitating re
Palumbo Júnior, Antonio; Da Costa, Nathalia Meireles; Esposito, Francesco; Fusco, Alfredo; Pinto, Luis Felipe Ribeiro
We have recently shown that HMGA2 is overexpressed in esophageal squamous cell carcinoma (ESCC) and its detection allows to discriminate between cancer and normal surrounding tissue proposing HMGA2 as a novel diagnostic marker. Interestingly, esophageal adenocarcinoma shows an opposite behavior with the overexpression of HMGA1 but not HMGA2. Moreover, we show that the suppression of HMGA2 in 2 ESCC cell lines reduces the malignant phenotype. Then, this paper highlights a differential induction of the HMGA proteins, depending on the cancer histological type, and reinforces the perspective of an innovative esophageal cancer therapy based on the suppression of the HMGA protein function and/or expression.
Adams, Richard J.; Lichter, Matthew D.; Krepkovich, Eileen T.; Ellington, Allison; White, Marga; Diamond, Paul T.
A study was conducted to investigate the criterion validity of measures of upper extremity (UE) motor function derived during practice of virtual activities of daily living (ADLs). Fourteen hemiparetic stroke patients employed a Virtual Occupational Therapy Assistant (VOTA), consisting of a high-fidelity virtual world and a Kinect™ sensor, in four sessions of approximately one hour in duration. An Unscented Kalman Filter-based human motion tracking algorithm estimated UE joint kinematics in real-time during performance of virtual ADL activities, enabling both animation of the user’s avatar and automated generation of metrics related to speed and smoothness of motion. These metrics, aggregated over discrete sub-task elements during performance of virtual ADLs, were compared to scores from an established assessment of UE motor performance, the Wolf Motor Function Test (WMFT). Spearman’s rank correlation analysis indicates a moderate correlation between VOTA-derived metrics and the time-based WMFT assessments, supporting the criterion validity of VOTA measures as a means of tracking patient progress during an UE rehabilitation program that includes practice of virtual ADLs. PMID:25265612
Ewen, Joshua B.; Lakshmanan, Balaji M.; Pillai, Ajay S.; McAuliffe, Danielle; Nettles, Carrie; Hallett, Mark; Crone, Nathan E.; Mostofsky, Stewart H.
Autism spectrum disorders (ASD) are thought to result in part from altered cortical excitatory-inhibitory balance; this pathophysiology may impact the generation of oscillations on electroencephalogram (EEG). We investigated premotor-parietal cortical physiology associated with praxis, which has strong theoretical and empirical associations with ASD symptomatology. Twenty five children with high-functioning ASD (HFA) and 33 controls performed a praxis task involving the pantomiming of tool use, while EEG was recorded. We assessed task-related modulation of signal power in alpha and beta frequency bands. Compared with controls, subjects with HFA showed 27% less left central (motor/premotor) beta (18–22 Hz) event-related desynchronization (ERD; p = 0.030), as well as 24% less left parietal alpha (7–13 Hz) ERD (p = 0.046). Within the HFA group, blunting of central ERD attenuation was associated with impairments in clinical measures of praxis imitation (r = −0.4; p = 0.04) and increased autism severity (r = 0.48; p = 0.016). The modulation of central beta activity is associated, among other things, with motor imagery, which may be necessary for imitation. Impaired imitation has been associated with core features of ASD. Altered modulation of oscillatory activity may be mechanistically involved in those aspects of motor network function that relate to the core symptoms of ASD. PMID:27199719
Batool, Sana; Soomro, Nabila; Amjad, Fareeha; Fauz, Rabia
Objective: To compare the effectiveness of constraint induced movement therapy versus motor relearning programme to improve motor function of hemiplegic upper extremity after stroke. Method: A sample of 42 patients was recruited from the Physiotherapy Department of IPM&R and Neurology OPD of Civil Hospital Karachi through non probability purposive sampling technique. Twenty one patients were placed to each experimental and control groups. Experimental group was treated with Constraint Induced Movement Therapy (CIMT) and control group was treated with motor relearning programme (MRP) for three consecutive weeks. Pre and post treatment measurements were determined by upper arm section of Motor Assessment Scale (MAS) and Self Care item of Functional Independence Measure (FIM) Scale. Results: Intra group analysis showed statistically significant results (p-value<0.05) in all items of MAS in both groups. However, advanced hand activities item of MAS in MRP group showed insignificant result (p-value=0.059). Self-care items of FIM Scale also showed significant result (p-value< 0.05) in both groups except dressing upper body item (p-value=0.059) in CIMT group and grooming and dressing upper body items (p-value=0.059 & 0.063) in MRP group showed insignificant p-values. Conclusion: CIMT group showed more significant improvement in motor function and self-care performance of hemiplegic upper extremity as compared to MRP group in patients with sub-acute stroke assessed by the MAS and FIM scales. Thus CIMT is proved to be more statistically significant and clinically effective intervention in comparison to motor relearning programme among the patients aged between 35-60 years. Further studies are needed to evaluate CIMT effects in acute and chronic post stroke population. PMID:26649007
Lindsay, Theodore; Sustar, Anne; Dickinson, Michael
Animals face the daunting task of controlling their limbs using a small set of highly constrained actuators. This problem is particularly demanding for insects such as Drosophila, which must adjust wing motion for both quick voluntary maneuvers and slow compensatory reflexes using only a dozen pairs of muscles. To identify strategies by which animals execute precise actions using sparse motor networks, we imaged the activity of a complete ensemble of wing control muscles in intact, flying flies. Our experiments uncovered a remarkably efficient logic in which each of the four skeletal elements at the base of the wing are equipped with both large phasically active muscles capable of executing large changes and smaller tonically active muscles specialized for continuous fine-scaled adjustments. Based on the responses to a broad panel of visual motion stimuli, we have developed a model by which the motor array regulates aerodynamically functional features of wing motion. VIDEO ABSTRACT.
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.
Gornicka-Pawlak, Elzbieta; Jabłońska, Anna; Chyliński, Andrzej; Domańska-Janik, Krystyna
The present study investigated influence of housing conditions on motor functions recovery and exploratory behavior following ouabain focal brain lesion in the rat. During 30 days post-surgery period rats were housed individually in standard cages (IS) or in groups in enriched environment (EE) and behaviorally tested. The EE lesioned rats showed enhanced recovery from motor impairments in walking beam task, comparing with IS animals. Contrarily, in the open field IS rats (both lesioned and control) traveled a longer distance, showed less habituation and spent less time resting at the home base than the EE animals. Unlike the EE lesioned animals, the lesioned IS rats, presented a tendency to hyperactivity in postinjury period. Turning tendency was significantly affected by unilateral brain lesion only in the EE rats. We can conclude that housing conditions distinctly affected the rat's behavior in classical laboratory tests.
Lee, MiHye; Ko, YoungJun; Shin, Mary Myong Sook; Lee, Wanhee
[Purpose] To investigate the effects of progressive functional training on lower limb muscle architecture and motor function of children with spastic cerebral palsy (CP). [Subjects] The subjects of this study were 26 children with spastic CP. [Methods] Thirteen subjects in the experimental group performed general neurodevelopmental treatment (NDT) and additional progressive functional trainings and 13 subjects in the control group performed only general NDT 3 times a week for 6 weeks. Ultrasonography, gross motor function measurement (GMFM) and the mobility questionnaire (MobQue) were evaluated. [Results] After the intervention, the muscle thickness of the quadriceps femoris (QF), cross-sectional area of the rectus femoris (RF), pennation angle of the gastrocnemius (GCM) and the MobQue score of the experimental group were significantly greater than those of the control group. The muscle thickness of QF correlated with the cross-sectional area (CSA) of RF and the pennation angle of GCM, and GMFM score correlated with the pennation angle of GCM. [Conclusion] Progressive functional training can increase muscle thickness, CSA, and the pennation angle of the lower limb muscles, and improve the mobility of spastic CP children making it useful as a practical adjunct to rehabilitation therapy. PMID:26157267
Kwon, Yong Hyun; Lee, Hye Young
[Purpose] The current study was designed to investigate the difference in lung capacity and muscle strengthening related to respiration depending on the level of the Gross Motor Function Classification System (GMFCS) in children with cerebral palsy (CP) through tests of respiratory function and respiratory pressure. [Subjects and Methods] A total of 49 children with CP who were classified as below level III of the GMFCS were recruited for this study. They were divided into three groups (i.e., GMFCS level I, GMFCS level II, and GMFCS level III). All children took the pulmonary function test (PFT) and underwent respiratory pressure testing for assessment of respiratory function in terms of lung capacity and respiratory muscle strength. [Results] The GMFCS level III group showed significantly lower scores for all tests of the PFT (i.e., forced vital capacity (FVC), forced expiratory volume at one second (FEV1), and slow vital capacity (SVC)) and testing for respiratory pressures (maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP)) compared with the other two groups. The results of post hoc analysis indicated that the GMFCS level III group differed significantly from the other two groups in terms of FVC, FEV1, MIP, and MEP. In addition, a significant difference in SVC was observed between GMFCS level II and III. [Conclusion] Children with CP who had relatively low motor function showed poor pulmonary capacity and respiratory muscle weakness. Therefore, clinical manifestations regarding lung capacity and respiratory muscle will be required in children with CP who demonstrate poor physical activity.
Gili, Tommaso; Fiori, Valentina; De Pasquale, Giada; Sabatini, Umberto; Caltagirone, Carlo; Marangolo, Paola
Recent studies have shown that the systematic and repetitive observation of actions belonging to the experiential human motor repertoire without verbal facilitation enhances the recovery of verbs in non fluent aphasia. However, it is still an open question whether this approach extends its efficacy also on discourse productivity by improving the retrieval of other linguistic units (i.e. nouns, sentences, content words). Moreover, nothing is known regarding the neural substrates which support the language recovery process due to action observation treatment.In the present study, ten non fluent aphasics were presented with two videoclips (real everyday life context vs. familiar pantomimed context), each video for six consecutive weeks (Monday to Friday, weekend off). During the treatment, they were asked to observe each video and to describe it without verbal facilitation from the therapist. In all patients, language measures were collected before and at the end of treatment. Before and after each treatment condition (real vs. pantomimed context), each subject underwent a resting state fMRI. After the treatment, significant changes in functional connectivity were found in right sensory-motor networks which were accompanied by a significant improvement for the different linguistic units in the real context condition. On the contrary, the language recovery obtained in the pantomimed context did not match any functional modification. The evidence for a recruitment of the sensory-motor cortices during the observation of actions embedded in real context suggests to potentially enhance language recovery in non fluent aphasia through a simulation process related to the sensory-motor properties of actions.
Dysphagia, or difficulty swallowing, is a common problem. Although most cases are attributable to benign disease processes, dysphagia is also a key symptom in several malignancies, making it an important symptom to evaluate. The differential diagnosis of dysphagia requires an understanding of deglutition, in particular the oropharyngeal versus esophageal stages. Stroke is the leading cause of oropharyngeal dysphagia, which is common in older adults and frequently presents as part of a broader complex of clinical manifestations. In esophageal dysphagia, difficulty swallowing is often the main complaint and is caused by localized neuromuscular disorders or obstructive lesions.
Prosperini, Luca; Piattella, Maria Cristina
Rehabilitation is recognized to be important in ameliorating motor and cognitive functions, reducing disease burden, and improving quality of life in patients with multiple sclerosis (MS). In this systematic review, we summarize the existing evidences that motor and cognitive rehabilitation may enhance functional and structural brain plasticity in patients with MS, as assessed by means of the most advanced neuroimaging techniques, including diffusion tensor imaging and task-related and resting-state functional magnetic resonance imaging (MRI). In most cases, the rehabilitation program was based on computer-assisted/video game exercises performed in either an outpatient or home setting. Despite their heterogeneity, all the included studies describe changes in white matter microarchitecture, in task-related activation, and/or in functional connectivity following both task-oriented and selective training. When explored, relevant correlation between improved function and MRI-detected brain changes was often found, supporting the hypothesis that training-induced brain plasticity is specifically linked to the trained domain. Small sample sizes, lack of randomization and/or an active control group, as well as missed relationship between MRI-detected changes and clinical performance, are the major drawbacks of the selected studies. Knowledge gaps in this field of research are also discussed to provide a framework for future investigations. PMID:26064692
Rasova, Kamila; Prochazkova, Marie; Tintera, Jaroslav; Ibrahim, Ibrahim; Zimova, Denisa; Stetkarova, Ivana
There is still little scientific evidence for the efficacy of neurofacilitation approaches and their possible influence on brain plasticity and adaptability. In this study, the outcome of a new kind of neurofacilitation approach, motor programme activating therapy (MPAT), was evaluated on the basis of a set of clinical functions and with MRI. Eighteen patients were examined four times with standardized clinical tests and diffusion tensor imaging to monitor changes without therapy, immediately after therapy and 1 month after therapy. Moreover, the strength of effective connectivity was analysed before and after therapy. Patients underwent a 1-h session of MPAT twice a week for 2 months. The data were analysed by nonparametric tests of association and were subsequently statistically evaluated. The therapy led to significant improvement in clinical functions, significant increment of fractional anisotropy and significant decrement of mean diffusivity, and decrement of effective connectivity at supplementary motor areas was observed immediately after the therapy. Changes in clinical functions and diffusion tensor images persisted 1 month after completing the programme. No statistically significant changes in clinical functions and no differences in MRI-diffusion tensor images were observed without physiotherapy. Positive immediate and long-term effects of MPAT on clinical and brain functions, as well as brain microstructure, were confirmed.
Abada, Yah-se K.; Nguyen, Huu Phuc; Schreiber, Rudy; Ellenbroek, Bart
Rationale Huntington disease (HD) is frequently first diagnosed by the appearance of motor symptoms; the diagnosis is subsequently confirmed by the presence of expanded CAG repeats (> 35) in the HUNTINGTIN (HTT) gene. A BACHD rat model for HD carrying the human full length mutated HTT with 97 CAG-CAA repeats has been established recently. Behavioral phenotyping of BACHD rats will help to determine the validity of this model and its potential use in preclinical drug discovery studies. Objectives The present study seeks to characterize the progressive emergence of motor, sensorimotor and cognitive deficits in BACHD rats. Materials and Methods Wild type and transgenic rats were tested from 1 till 12 months of age. Motor tests were selected to measure spontaneous locomotor activity (open field) and gait coordination. Sensorimotor gating was assessed in acoustic startle response paradigms and recognition memory was evaluated in an object recognition test. Results Transgenic rats showed hyperactivity at 1 month and hypoactivity starting at 4 months of age. Motor coordination imbalance in a Rotarod test was present at 2 months and gait abnormalities were seen in a Catwalk test at 12 months. Subtle sensorimotor changes were observed, whereas object recognition was unimpaired in BACHD rats up to 12 months of age. Conclusion The current BACHD rat model recapitulates certain symptoms from HD patients, especially the marked motor deficits. A subtle neuropsychological phenotype was found and further studies are needed to fully address the sensorimotor phenotype and the potential use of BACHD rats for drug discovery purposes. PMID:23874679
The rapidly expanding population of older adults raises concern in EPA over aging-related vulnerability to environmental exposures. Deficits in motor function are frequent with advancing age. An increase in interindividual variability is also commonly accepted. Increased variabil...
Moawad, Fouad J; Cheng, Edaire; Schoepfer, Alain; Al-Haddad, Sahar; Bellizzi, Andrew M; Dawson, Heather; El-Zimaity, Hala; Guindi, Maha; Penagini, Roberto; Safrooneva, Ekaterina; Chehade, Mirna
Eosinophilic esophagitis (EoE) is a chronic antigen-mediated immune disease of the esophagus characterized by symptoms related to esophageal dysfunction, as well as significant esophageal eosinophilia. Although dense eosinophilia is the hallmark of EoE, other characteristic histologic features have been described that may help distinguish EoE from other competing diagnoses, although none are specific to EoE. One or more foods and, at times, environmental allergens trigger EoE. Left untreated, esophageal inflammation in EoE may lead to esophageal remodeling and stricture formation. Symptoms in EoE vary with age, as they relate to the progression of the disease from an inflammatory to a fibrostenotic phenotype over time. There are currently no U.S. Food and Drug Administration-approved therapies for EoE. Current options include various dietary-restriction therapies, topical corticosteroids, and esophageal dilations. Several emerging therapies aiming at restoring the esophageal barrier function or targeting various inflammatory cells or their mediators are under investigation.
Pierella, Camilla; Abdollahi, Farnaz; Farshchiansadegh, Ali; Pedersen, Jessica; Thorp, Elias; Mussa-Ivaldi, Ferdinando A.; Casadio, Maura
The concept of human motor redundancy attracted much attention since the early studies of motor control, as it highlights the ability of the motor system to generate a great variety of movements to achieve any single well-defined goal. The abundance of degrees of freedom in the human body may be a fundamental resource in the learning and remapping problems that are encountered in human–machine interfaces (HMIs) developments. The HMI can act at different levels decoding brain signals or body signals to control an external device. The transformation from neural signals to device commands is the core of research on brain-machine interfaces (BMIs). However, while BMIs bypass completely the final path of the motor system, body-machine interfaces (BoMIs) take advantage of motor skills that are still available to the user and have the potential to enhance these skills through their consistent use. BoMIs empower people with severe motor disabilities with the possibility to control external devices, and they concurrently offer the opportunity to focus on achieving rehabilitative goals. In this study we describe a theoretical paradigm for the use of a BoMI in rehabilitation. The proposed BoMI remaps the user’s residual upper body mobility to the two coordinates of a cursor on a computer screen. This mapping is obtained by principal component analysis (PCA). We hypothesize that the BoMI can be specifically programmed to engage the users in functional exercises aimed at partial recovery of motor skills, while simultaneously controlling the cursor and carrying out functional tasks, e.g. playing games. Specifically, PCA allows us to select not only the subspace that is most comfortable for the user to act upon, but also the degrees of freedom and coordination patterns that the user has more difficulty engaging. In this article, we describe a family of map modifications that can be made to change the motor behavior of the user. Depending on the characteristics of the
Jahnsen, Reidun; Aamodt, Geir; Rosenbaum, Peter
The present study investigated the reliability of self-reported rating of Gross Motor Function Classification System (GMFCS) levels compared with professional rating, and changes in gross motor function over time, in adults with cerebral palsy. Twenty-nine females and 33 males aged between 18 years 5 months and 62 years 11 months (mean age 34y 7mo [SD 10y 6mo]) participated in the study. Participants rated their current gross motor function using the GMFCS and reported their judgement of their gross motor function at age 10 to 12 years. The project leader, a physical therapist, also classified participants' current GMFCS levels and conducted a chart review on all accessible medical records of participants' gross motor function when they were 10 to 12 years old, rating the GMFCS level accordingly. Intraclass correlation coefficients (ICC) between self-reported and professional ratings showed excellent agreement (ICC=0.93-0.95, 95% confidence interval [CI] 0.89-0.97). More than half the participants experienced a stable gross motor function from the age of 10 to 12 years to the present. Those at GMFCS Levels II and III at the age of 10 to 12 years (according to the professional rating) had significant change for the worse in gross motor function over time, with odds ratios of 9.30 (95% CI 1.2-73.0, p=0.03) and 7.00 (95% CI 1.1-43.0, p=0.04) respectively. Interview data on circumstances regarding changes in gross motor function since childhood are also reported. Changes in GMFCS level were mostly associated with physical or social environmental factors.
Huang, Zonghao; Wang, Zhigong; Lv, Xiaoying; Zhou, Yuxuan; Wang, Haipeng; Zong, Sihao
Hemiparesis is one of the most common consequences of stroke. Advanced rehabilitation techniques are essential for restoring motor function in hemiplegic patients. Functional electrical stimulation applied to the affected limb based on myoelectric signal from the unaffected limb is a promising therapy for hemiplegia. In this study, we developed a prototype system for evaluating this novel functional electrical stimulation-control strategy. Based on surface electromyography and a vector machine model, a self-administered, multi-movement, force-modulation functional electrical stimulation-prototype system for hemiplegia was implemented. This paper discusses the hardware design, the algorithm of the system, and key points of the self-oscillation-prone system. The experimental results demonstrate the feasibility of the prototype system for further clinical trials, which is being conducted to evaluate the efficacy of the proposed rehabilitation technique.
Stage IB Esophageal Adenocarcinoma; Stage IIA Esophageal Adenocarcinoma; Stage IIB Esophageal Adenocarcinoma; Stage IIIA Esophageal Adenocarcinoma; Stage IIIB Esophageal Adenocarcinoma; Stage IIIC Esophageal Adenocarcinoma
Marongiu, Roberta; Arango-Lievano, Margarita; Francardo, Veronica; Morgenstern, Peter; Zhang, Xiaoqun; Cenci, M. Angela; Svenningsson, Per; Greengard, Paul; Kaplitt, Michael G.
Complications of dopamine replacement for Parkinson’s disease (PD) can limit therapeutic options, leading to interest in identifying novel pathways that can be exploited to improve treatment. p11 (S100A10) is a cellular scaffold protein that binds to and potentiates the activity of various ion channels and neurotransmitter receptors. We have previously reported that p11 can influence ventral striatal function in models of depression and drug addiction, and thus we hypothesized that dorsal striatal p11 might mediate motor function and drug responses in parkinsonian mice. To focally inhibit p11 expression in the dorsal striatum, we injected an adeno-associated virus (AAV) vector producing a short hairpin RNA (AAV.sh.p11). This intervention reduced the impairment in motor function on forced tasks, such as rotarod and treadmill tests, caused by substantia nigra lesioning in mice. Measures of spontaneous movement and gait in an open-field test declined as expected in control lesioned mice, whereas AAV.sh.p11 mice remained at or near normal baseline. Mice with unilateral lesions were then challenged with l-dopa (levodopa) and various dopamine receptor agonists, and resulting rotational behaviors were significantly reduced after ipsilateral inhibition of dorsal striatal p11 expression. Finally, p11 knockdown in the dorsal striatum dramatically reduced l-dopa–induced abnormal involuntary movements compared with control mice. These data indicate that focal inhibition of p11 action in the dorsal striatum could be a promising PD therapeutic target to improve motor function while reducing l-dopa–induced dyskinesias. PMID:26787858
Marongiu, Roberta; Arango-Lievano, Margarita; Francardo, Veronica; Morgenstern, Peter; Zhang, Xiaoqun; Cenci, M Angela; Svenningsson, Per; Greengard, Paul; Kaplitt, Michael G
Complications of dopamine replacement for Parkinson's disease (PD) can limit therapeutic options, leading to interest in identifying novel pathways that can be exploited to improve treatment. p11 (S100A10) is a cellular scaffold protein that binds to and potentiates the activity of various ion channels and neurotransmitter receptors. We have previously reported that p11 can influence ventral striatal function in models of depression and drug addiction, and thus we hypothesized that dorsal striatal p11 might mediate motor function and drug responses in parkinsonian mice. To focally inhibit p11 expression in the dorsal striatum, we injected an adeno-associated virus (AAV) vector producing a short hairpin RNA (AAV.sh.p11). This intervention reduced the impairment in motor function on forced tasks, such as rotarod and treadmill tests, caused by substantia nigra lesioning in mice. Measures of spontaneous movement and gait in an open-field test declined as expected in control lesioned mice, whereas AAV.sh.p11 mice remained at or near normal baseline. Mice with unilateral lesions were then challenged with l-dopa (levodopa) and various dopamine receptor agonists, and resulting rotational behaviors were significantly reduced after ipsilateral inhibition of dorsal striatal p11 expression. Finally, p11 knockdown in the dorsal striatum dramatically reduced l-dopa-induced abnormal involuntary movements compared with control mice. These data indicate that focal inhibition of p11 action in the dorsal striatum could be a promising PD therapeutic target to improve motor function while reducing l-dopa-induced dyskinesias.
Rehme, Anne K; Volz, Lukas J; Feis, Delia-Lisa; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian
Several neurobiological factors have been found to correlate with functional recovery after brain lesions. However, predicting the individual potential of recovery remains difficult. Here we used multivariate support vector machine (SVM) classification to explore the prognostic value of functional magnetic resonance imaging (fMRI) to predict individual motor outcome at 4-6 months post-stroke. To this end, 21 first-ever stroke patients with hand motor deficits participated in an fMRI hand motor task in the first few days post-stroke. Motor impairment was quantified assessing grip force and the Action Research Arm Test. Linear SVM classifiers were trained to predict good versus poor motor outcome of unseen new patients. We found that fMRI activity acquired in the first week post-stroke correctly predicted the outcome for 86% of all patients. In contrast, the concurrent assessment of motor function provided 76% accuracy with low sensitivity (<60%). Furthermore, the outcome of patients with initially moderate impairment and high outcome variability could not be predicted based on motor tests. In contrast, fMRI provided 87.5% prediction accuracy in these patients. Classifications were driven by activity in ipsilesional motor areas and contralesional cerebellum. The accuracy of subacute fMRI data (two weeks post-stroke), age, time post-stroke, lesion volume, and location were at 50%-chance-level. In conclusion, multivariate decoding of fMRI data with SVM early after stroke enables a robust prediction of motor recovery. The potential for recovery is influenced by the initial dysfunction of the active motor system, particularly in those patients whose outcome cannot be predicted by behavioral tests.
Silva, D; Santos, F; Piedade, S; Morais-Almeida, M
Eosinophilic esophagitis (EoE) is an inflammatory immune-mediated disease with predominant eosinophilic inflammation characterized by the presence of esophageal dysfunction symptoms. Treatment delay can be associated with disease complications, like esophageal strictures, that can justify the use of invasive procedures which are not deprived of side effects. We present a case report of a 14 year old child with severe esophageal stricture secondary to EoE, that was treated with topical and systemic corticosteroid before any invasive procedure was considered. After 26 weeks of medical treatment, significant improvement of esophageal dysfunction occurred with histological remission and stricture resolution. In patients with severe esophageal strictures secondary to EoE, the need for esophageal dilation procedures should be considered only after anti-inflammatory treatment.
Mallory, Grant W.; Grahn, Peter J.; Hachmann, Jan T.; Lujan, J. Luis; Lee, Kendall H.
Spinal cord injury (SCI) can be defined as a loss of communication between the brain and the body due to disrupted pathways within the spinal cord. While many promising molecular strategies have emerged to reduce secondary injury and promote axonal regrowth, there is still no effective cure and recovery of function remains limited. Functional electrical stimulation (FES) represents a strategy developed to restore motor function without the need for regenerating severed spinal pathways. Despite its technological success, however, FES has not been widely integrated into the lives of spinal cord injury survivors. In this review, we briefly discuss the limitations of existing FES technologies. Additionally, we discuss how optogenetics, a rapidly evolving technique used primarily to investigate select neuronal populations within the brain, may eventually be used to replace FES as a form of therapy for functional restoration following SCI. PMID:25659246
Objective To assess the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) on balance function in patients with chronic stroke. Methods Thirty participants with chronic stroke were enrolled in this study. High frequency (10 Hz) rTMS was delivered with butterfly-coil on trunk motor spot. Each patient received both real and sham rTMS in a random sequence. The rTMS cycles (real or sham) were composed of 10 sessions each, administered over two weeks, and separated by a 4-week washout period. Balance function was measured by Berg Balance Scale and computerized dynamic posturography to determine the effect of rTMS before and one day after the end of each treatment period, as well as at a 1-month follow-up. Results The balance function was significantly improved after high frequency rTMS as compared with that after sham rTMS (p<0.05). There was no serious adverse effect in patients during the treatment period. Conclusion In the chronic stroke patients, high frequency rTMS to the trunk motor area seems to be a helpful way to improve balance function without any specific adverse effects. Further studies are needed to identify the underlying mechanism and generate a detailed protocol. PMID:27847712
Yu, Lili; Huang, Qiuchen; Hu, Chunying; Ye, Miao
[Purpose] The purpose of this study was to explore the immediate effects of different frequencies of auditory stimulation on the lower limb motor function of healthy people. [Subjects and Methods] The subjects were 7 healthy people (5 males and 2 females). The subjects’ lower limb function was measured without auditory stimulation (control), and with auditory stimulation of 500, 1,000, 1,500, and 2,000 Hz. The measured parameters were maximum knee extension torque, average knee extension torque, the Timed Up and Go test (TUG) time, Functional Reach (FR), and the 10-meter walking time. [Results] The TUG times of 500, 1,500, and 2,000 Hz auditory stimulation showed significant decreases compared to the control. The 10-m walking times of 1,000 and 2,000 Hz auditory stimulation showed significant decreases compared to the control. [Conclusion] The results show that auditory stimulation improved the TUG and 10-meter walking times of healthy people and that different frequencies of auditory stimulation had different effects on lower limb motor function. PMID:27630392
Zhou, F. Q.; Tan, Y. M.; Wu, L.; Zhuang, Y.; He, L. C.; Gong, H. H.
Several neuroimaging studies have suggested brain reorganisation in patients with cervical spondylotic myelopathy (CSM); however, the changes in spontaneous neuronal activity that are associated with connectedness remain largely unknown. In this study, functional connectivity strength (FCS), a data-driven degree centrality method based on a theoretical approach, was applied for the first time to investigate changes in the sensory-motor network (SMN) at the voxel level. Comparatively, CSM not only showed significantly decreased FCS in the operculum-integrated regions, which exhibited reduced resting-state functional connectivity (rsFC) around the Rolandic sulcus, but it also showed increased FCS in the premotor, primary somatosensory, and parietal-integrated areas, which primarily showed an enhanced rsFC pattern. Correlation analysis showed that altered FCS (in the left premotor-ventral/precentral-operculum, right operculum-parietale 4, and right S1) was associated with worsening Japanese Orthopaedic Association scores and that the rsFC pattern was influenced by cervical cord micro-structural damage at the C2 level. Together, these findings suggest that during myelopathy, the intrinsic functional plasticity of the SMN responds to the insufficient sensory and motor experience in CSM patients. This knowledge may improve our understanding of the comprehensive functional defects found in CSM patients and may inspire the development of new therapeutic strategies in the future. PMID:25897648
Chang, Ming-Wen; Young, Ming-Shing; Lin, Mao-Tsun
This study describes a high-accuracy inclined plane test system for quantitative measurement of the limb motor function of laboratory rats. The system is built around a microcontroller and uses a stepping motor to drive a ball screw, which changes the angle of the inclined plane. Any of the seven inclination speeds can be selected by the user. Two infrared (IR) LED/detector pairs function as interrupt sensors for objective determination of the moment that the rat loses its grip on the textured flooring of the starting area and slips down the plane. Inclination angle at the moment of IR interrupt (i.e. rat slip) is recorded. A liquid crystal display module shows the inclination speed and the inclination angle. The system can function as a stand alone device but a RS232 port allows connection to a personal computer (PC), so data can be sent directly to hard disk for storage and analysis. Experiments can be controlled by a local keypad or by the connected PC. Advantages of the presented system include easy operation, high accuracy, non-dependence on human observation for determination of slip angle, stand-alone capability, low cost and easy modification of the controlling software for different types of experiments. A fully functional prototype of the system is described. The prototype was used experimentally by a hospital group testing traumatic brain injury experiments, and some of their results are presented for system verification. It is found that the system is stable, accurate and easily used by investigators.
Han, Qi; Cao, Changshu; Ding, Yuetong; So, Kwok-Fai; Wu, Wutian; Qu, Yibo; Zhou, Libing
Despite the obvious clinical interest, our understanding of how developmental mechanisms are redeployed during degeneration and regeneration after brain and spinal cord injuries remains quite rudimentary. In animal models of spinal cord injury, although spontaneous regeneration of descending axons is limited, compensation by intact corticospinal axons, descending tracts from the brainstem, and local intrinsic spinal networks all contribute to the recovery of motor function. Here, we investigated spontaneous motor compensation and plasticity that occur in the absence of corticospinal tract, using Celsr3|Emx1 mice in which the corticospinal tract is completely and specifically absent as a consequence of Celsr3 inactivation in the cortex. Mutant mice had no paresis, but displayed hyperactivity in open-field, and a reduction in skilled movements in food pellet manipulation tests. The number of spinal motoneurons was reduced and their terminal arbors at neuromuscular junctions were atrophic, which was reflected in electromyography deficits. Rubrospinal projections, calretinin-positive propriospinal projections, afferent innervation of motoneurons by calretinin-positive segmental interneurons, and terminal ramifications of monoaminergic projections were significantly increased. Contrary to control animals, mutants also developed a severe and persistent disability of forelimb use following the section of the rubrospinal tract at the C4 spinal level. These observations demonstrate for the first time that the congenital absence of the corticospinal tract induces spontaneous plasticity, both at the level of the motor spinal cord and in descending monoaminergic and rubrospinal projections. Such compensatory mechanisms could be recruited in case of brain or spinal cord lesion or degeneration.
Alaverdashvili, Mariam; Hackett, Mark J; Caine, Sally; Paterson, Phyllis G
While protein-energy malnutrition in the adult has been reported to induce motor abnormalities and exaggerate motor deficits caused by stroke, it is not known if alterations in mature cortical neurons contribute to the functional deficits. Therefore, we explored if PEM in adult rats provoked changes in the biochemical profile of neurons in the forelimb and hindlimb regions of the motor cortex. Fourier transform infrared spectroscopic imaging using a synchrotron generated light source revealed for the first time altered lipid composition in neurons and subcellular domains (cytosol and nuclei) in a cortical layer and region-specific manner. This change measured by the area under the curve of the δ(CH2) band may indicate modifications in membrane fluidity. These PEM-induced biochemical changes were associated with the development of abnormalities in forelimb use and posture. The findings of this study provide a mechanism by which PEM, if not treated, could exacerbate the course of various neurological disorders and diminish treatment efficacy.
McLeod, Kevin R; Langevin, Lisa Marie; Goodyear, Bradley G; Dewey, Deborah
Developmental coordination disorder (DCD) and attention deficit/hyperactivity disorder (ADHD) are prevalent childhood disorders that frequently co-occur. Evidence from neuroimaging research suggests that children with these disorders exhibit disruptions in motor circuitry, which could account for the high rate of co-occurrence. The primary objective of this study was to investigate the functional connections of the motor network in children with DCD and/or ADHD compared to typically developing controls, with the aim of identifying common neurophysiological substrates. Resting-state fMRI was performed on seven children with DCD, 21 with ADHD, 18 with DCD + ADHD and 23 controls. Resting-state connectivity of the primary motor cortex was compared between each group and controls, using age as a co-factor. Relative to controls, children with DCD and/or ADHD exhibited similar reductions in functional connectivity between the primary motor cortex and the bilateral inferior frontal gyri, right supramarginal gyrus, angular gyri, insular cortices, amygdala, putamen, and pallidum. In addition, children with DCD and/or ADHD exhibited different age-related patterns of connectivity, compared to controls. These findings suggest that children with DCD and/or ADHD exhibit disruptions in motor circuitry, which may contribute to problems with motor functioning and attention. Our results support the existence of common neurophysiological substrates underlying both motor and attention problems.
Hatem, Samar M.; Saussez, Geoffroy; della Faille, Margaux; Prist, Vincent; Zhang, Xue; Dispa, Delphine; Bleyenheuft, Yannick
Stroke is one of the leading causes for disability worldwide. Motor function deficits due to stroke affect the patients' mobility, their limitation in daily life activities, their participation in society and their odds of returning to professional activities. All of these factors contribute to a low overall quality of life. Rehabilitation training is the most effective way to reduce motor impairments in stroke patients. This multiple systematic review focuses both on standard treatment methods and on innovating rehabilitation techniques used to promote upper extremity motor function in stroke patients. A total number of 5712 publications on stroke rehabilitation was systematically reviewed for relevance and quality with regards to upper extremity motor outcome. This procedure yielded 270 publications corresponding to the inclusion criteria of the systematic review. Recent technology-based interventions in stroke rehabilitation including non-invasive brain stimulation, robot-assisted training, and virtual reality immersion are addressed. Finally, a decisional tree based on evidence from the literature and characteristics of stroke patients is proposed. At present, the stroke rehabilitation field faces the challenge to tailor evidence-based treatment strategies to the needs of the individual stroke patient. Interventions can be combined in order to achieve the maximal motor function recovery for each patient. Though the efficacy of some interventions may be under debate, motor skill learning, and some new technological approaches give promising outcome prognosis in stroke motor rehabilitation. PMID:27679565
Bustamante, Juanita; Karadayian, Analia G; Lores-Arnaiz, Silvia; Cutrera, Rodolfo A
Ethanol has been known to affect various behavioral parameters in experimental animals, even several hours after ethanol (EtOH) is absent from blood circulation, in the period known as hangover. The aim of this study was to assess the effects of acute ethanol hangover on motor performance in association with the brain cortex energetic metabolism. Evaluation of motor performance and brain cortex mitochondrial function during alcohol hangover was performed in mice 6 hours after a high ethanol dose (hangover onset). Animals were injected i.p. either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover group). Ethanol hangover group showed a bad motor performance compared with control animals (p < .05). Oxygen uptake in brain cortex mitochondria from hangover animals showed a 34% decrease in the respiratory control rate as compared with the control group. Mitochondrial complex activities were decreased being the complex I-III the less affected by the hangover condition; complex II-III was markedly decreased by ethanol hangover showing 50% less activity than controls. Complex IV was 42% decreased as compared with control animals. Hydrogen peroxide production was 51% increased in brain cortex mitochondria from the hangover group, as compared with the control animals. Quantification of the mitochondrial transmembrane potential indicated that ethanol injected animals presented 17% less ability to maintain the polarized condition as compared with controls. These results indicate that a clear decrease in proton motive force occurs in brain cortex mitochondria during hangover conditions. We can conclude that a decreased motor performance observed in the hangover group of animals could be associated with brain cortex mitochondrial dysfunction and the resulting impairment of its energetic metabolism.
Eastwood, G.L.; Braverman, L.E.; White, E.M.; Vander Salm, T.J.
A 65-year-old woman suffered from both chronic gastroesophageal reflux, which was complicated by columnar metaplasia (Barrett's epithelium), and profound hypothyroidism. An esophageal motility tracing showed absence of peristalsis in the lower esophagus and the lower esophageal sphincter (LES) could not be identified. Thyroid replacement therapy, in conjunction with antacid and cimetidine treatment, was associated not only with improvement in the gastroesophageal reflux symptoms, but also with a return of esophageal peristalsis and LES pressure to normal. To support our clinical observations, we rendered four cats hypothyroid with /sup 131/I and documented a fall in LES pressure. We propose that abnormal smooth-muscle function of the esophagus may be another manifestation of the gastrointestinal motility disturbances which are associated with hypothyroidism.
Noterdaeme, Michele; Wriedt, Elke; Höhne, Christian
The objective of this study is to compare the cognitive profile, the motor and language functioning and the psychosocial adaptation of children with Asperger syndrome (AS) and with high-functioning autism (HFA). Subjects were recruited through the department Autism and Developmental Disorders of the Heckscher-Klinikum. To be included in the study, the full-scale-IQ had to be at least 80. Subjects with AS had to have a normal early language development and subjects with HFA a clear delay in language development, as reported by their parents. The sample consisted of 57 children with Asperger syndrome and 55 children with high-functioning autism. The mean age of the children was 10 years. All subjects were examined with a standardised test battery. Children with AS had a higher full-scale-IQ than children with HFA. This was due to a higher verbal-IQ. There were no significant differences in the performance-IQ. At a mean age of 10 years, subjects with AS had better language skills than subjects with HFA, but at least 30% showed clear receptive language problems. Motor problems were present in about 50% of the children with AS and HFA. The level of psychosocial adaptation was clearly reduced, but was comparable for the two groups. The differences in verbal-IQ and language skills between the two groups could be explained through the definition of the syndromes. The presence of language problems in the subjects with AS at age 10, the comparable degree of motor impairment and level of psychosocial adaptation question the validity of the distinction between AS and HFA within the category of pervasive developmental disorders.
Hellendoorn, Annika; Wijnroks, Lex; van Daalen, Emma; Dietz, Claudine; Buitelaar, Jan K; Leseman, Paul
In order to understand typical and atypical developmental trajectories it is important to assess how strengths or weaknesses in one domain may be affecting performance in other domains. This study examined longitudinal relations between early fine motor functioning, visuospatial cognition, exploration, and language development in preschool children with ASD and children with other developmental delays/disorders. The ASD group included 63 children at T1 (Mage = 27.10 months, SD = 8.71) and 46 children at T2 (Mage = 45.85 months, SD = 7.16). The DD group consisted of 269 children at T1 (Mage = 17.99 months, SD = 5.59), and 121 children at T2 (Mag e= 43.51 months, SD = 3.81). A subgroup nested within the total sample was randomly selected and studied in-depth on exploratory behavior. This group consisted of 50 children, 21 children with ASD (Mage = 27.57, SD = 7.09) and 29 children with DD (Mage = 24.03 months, SD = 6.42). Fine motor functioning predicted language in both groups. Fine motor functioning was related to visuospatial cognition in both groups and related to object exploration, spatial exploration, and social orientation during exploration only in the ASD group. Visuospatial cognition and all exploration measures were related to both receptive and expressive language in both groups. The findings are in line with the embodied cognition theory, which suggests that cognition emerges from and is grounded in the bodily interactions of an agent with the environment. This study emphasizes the need for researchers and clinicians to consider cognition as emergent from multiple interacting systems.
Ziereis, Susanne; Jansen, Petra
Children with Attention-Deficit/Hyperactivity Disorder (ADHD) often show major deficits in motor and cognitive abilities. Pharmacological treatment is commonly used to reduce ADHD symptoms. However, non-pharmacologic treatment methods would be preferred by parents, children and psychiatrists. Physical activity (PA) has been demonstrated to improve cognitive functioning in healthy populations. It can be hypothesized that there are similar beneficial effects in children with ADHD, however, very little is known about this issue. The purpose of the present study was to determine whether PA improves cognitive performance in children with ADHD. A total of 43 children with ADHD (32 boys and 11 girls) aged between seven and 12 years took part in the study. To investigate whether potential effects on executive functioning depend on the kind of PA, two different 12-week training programs were implemented. The study-design consisted of two experimental groups (EG1, n=13; EG2, n=14) and a wait-list control group (CG, n=16). Participants in EG1 took part in a training which focused on the abilities ball handling, balance and manual dexterity. Participants in EG2 group were trained in sports without a specific focus. The children in the CG group received no intervention. Participants completed assessments of working memory (WM) and motor performance before, immediately after the first training week and one week after the last session. After the 12-week intervention period, several measures of the EG1 and EG2s significantly improved over time. Furthermore, between group comparisons demonstrated significant improvements in both EG1 and EG2 compared to the CG in variables assessing WM performance and motor performance. These findings support the hypothesis that long-term PA has a positive effect on executive functions of children with ADHD, regardless of the specificity of the PA. The outcomes indicated that regular PA can be used as a complementary or alternative non
Williams, Jacqueline; Reid, Susan M.; Reddihough, Dinah S.; Anderson, Vicki
In addition to motor execution problems, children with hemiplegia have motor planning deficits, which may stem from poor motor imagery ability. This study aimed to provide a greater understanding of motor imagery ability in children with hemiplegia using the hand rotation task. Three groups of children, aged 8-12 years, participated: right…
Khalaf, Asseel; Hoad, Caroline L; Spiller, Robin C; Gowland, Penny A; Moran, Gordon W; Marciani, Luca
Magnetic resonance imaging (MRI) is a well established technique that has revolutionized diagnostic radiology. Until recently, the impact that MRI has had in the assessment of gastrointestinal motor function and bowel fluid distribution in health and in disease has been more limited, despite the novel insights that MRI can provide along the entire gastrointestinal tract. MRI biomarkers include intestinal motility indices, small bowel water content and whole gut transit time. The present review discusses new developments and applications of MRI in the upper gastrointestinal tract, the small bowel and the colon reported in the literature in the last 5 years. PMID:26600972
Cho, Sangjin; Shahriar, Md Rifat; Chong, Uipil
For the analysis of non-stationary signals generated by a non-linear process like fault of an induction motor, empirical mode decomposition (EMD) is the best choice as it decomposes the signal into its natural oscillatory modes known as intrinsic mode functions (IMFs). However, some of these oscillatory modes obtained from a fault signal are not significant as they do not bear any fault signature and can cause misclassification of the fault instance. To solve this issue, a novel IMF selection algorithm is proposed in this work.
Möller, Harald E.; Sieger, Tomáš; Schroeter, Matthias L.; Vymazal, Josef; Růžička, Evžen; Jech, Robert
To tackle the heterogeneity of Parkinson’s disease symptoms, most functional imaging studies tend to select a uniform group of subjects. We hypothesize that more profound considerations are needed to account for intra/inter-subject clinical variability and possibly for differing pathophysiological processes. Twelve patients were investigated using functional magnetic resonance imaging during visually-guided finger tapping. To account for disease heterogeneity, the motor score and individual symptom scores from the Unified Parkinson’s Disease Rating Scale (UPDRS-III) were utilized in the group-level model using two approaches either as the explanatory variable or as the effect of interest. Employment of the UPDRS-III score and symptom scores was systematically tested on the resulting group response to the levodopa challenge, which further accentuated the diversity of the diseased state of participants. Statistics revealed a bilateral group response to levodopa in the basal ganglia. Interestingly, systematic incorporation of individual motor aspects of the disease in the modelling amended the resulting activity patterns conspicuously, evidencing a manifold amount of explained variability by the particular score. In conclusion, the severity of clinical symptoms expressed in the UPDRS-III scores should be considered in the analysis to attain unbiased statistics, draw reliable conclusions and allow for comparisons between research groups studying Parkinson’s disease using functional magnetic resonance imaging. PMID:23418522
Starosta, Michał; Redlicka, Justyna; Brzeziański, Michał; Niwald, Marta; Miller, Elżbieta
Diseases of the central nervous system are the most common cause of mobility and cognitive impairment. Stroke is the leading cause of hospitalization in the Neurological Rehabilitation Departments. Age increases the risk of stroke, therefore monitoring basic medical parameters, including blood pressure especially under age of 65, is a very important part of preventive healthcare. According to data from the National Association of Stroke, in 10% of patients after brain stroke, recovery of motor functions and mental state is almost complete, in 25% impairment is minimal, in 40% the functional and cognitive disability is moderated or significant therefore requires rehabilitation, in 10% in view of impossibility of active rehabilitation patients requires comprehensive nursing care service at home or in special long term care centers. Early mortality after stroke is about 15% of patients. Neurological rehabilitation after the incident of stroke is based on a multidisciplinary, individual approach to the problems arising directly from the consequences of stroke as well as comorbidities and social conditions and welfare in order to enable the best level of functioning at home and in society. The article discusses motor and cognitive impairment, which is important from neurological rehabilitation point of view as well as opportunities for their improvement. In addition, the work includes a description of the major risk factors for stroke, together with chosen predisposing genes statement.
Liu, Jian; Yang, Xiao-yu; Xia, Wei-wei; Dong, Jian; Yang, Mao-guang; Jiao, Jian-hang
Following central nervous system injury, axonal sprouts form distal to the injury site and extend into the denervated area, reconstructing neural circuits through neural plasticity. How to facilitate this plasticity has become the key to the success of central nervous system repair. It remains controversial whether fine motor skill training contributes to the recovery of neurological function after spinal cord injury. Therefore, we established a rat model of unilateral corticospinal tract injury using a pyramidal tract cutting method. Horizontal ladder crawling and food ball grasping training procedures were conducted 2 weeks before injury and 3 days after injury. The neurological function of rat forelimbs was assessed at 1, 2, 3, 4, and 6 weeks after injury. Axon growth was observed with biotinylated dextran amine anterograde tracing in the healthy corticospinal tract of the denervated area at different time periods. Our results demonstrate that compared with untrained rats, functional recovery was better in the forelimbs and forepaws of trained rats. The number of axons and the expression of growth associated protein 43 were increased at the injury site 3 weeks after corticospinal tract injury. These findings confirm that fine motor skill training promotes central nervous system plasticity in spinal cord injury rats. PMID:28197197
Fraiman, D; Miranda, M F; Erthal, F; Buur, P F; Elschot, M; Souza, L; Rombouts, S A R B; Schimmelpenninck, C A; Norris, D G; Malessy, M J A; Galves, A; Vargas, C D
This study aims at the effects of traumatic brachial plexus lesion with root avulsions (BPA) upon the organization of the primary motor cortex (M1). Nine right-handed patients with a right BPA in whom an intercostal to musculocutaneous (ICN-MC) nerve transfer was performed had post-operative resting state fMRI scanning. The analysis of empirical functional correlations between neighboring voxels revealed faster correlation decay as a function of distance in the M1 region corresponding to the arm in BPA patients as compared to the control group. No differences between the two groups were found in the face area. We also investigated whether such larger decay in patients could be attributed to a gray matter diminution in M1. Structural imaging analysis showed no difference in gray matter density between groups. Our findings suggest that the faster decay in neighboring functional correlations without significant gray matter diminution in BPA patients could be related to a reduced activity in intrinsic horizontal connections in M1 responsible for upper limb motor synergies.
Park, Si-Eun; Oh, Dae-Sik; Moon, Sang-Hyun
[Purpose] The purpose of this study was to identify the effects of oculo-motor exercise, functional electrical stimulation (FES), and proprioceptive neuromuscular facilitation (PNF) on the visual perception of spatial neglect patients. [Subjects and Methods] The subjects were randomly allocated to 3 groups: an oculo-motor exercise (OME) group, a FES with oculo-motor exercise (FOME) group, and a PNF with oculo-motor exercise (POME) group. The line bisection test (LBT), motor free visual test (MVPT), and Catherine Bergego Scale (CBS) were used to measure visual perception. These were performed 5 times per week for 6 weeks. [Results] The OME group and POME group showed significant improvements according to the LBT and MVPT results, but the FOME group showed no significant improvement. According to the CBS, all 3 groups showed significant improvements. The OME and POME groups showed improvement over the FOME group in the LBT and MVPT. However, there was no significant difference among the three groups according to the CBS. [Conclusion] These results indicate that oculo-motor exercise and PNF with oculo-motor exercise had more positive effects than FES with oculo-motor exercise on the visual perception of spatial neglect patients.
Park, Si-Eun; Oh, Dae-Sik; Moon, Sang-Hyun
[Purpose] The purpose of this study was to identify the effects of oculo-motor exercise, functional electrical stimulation (FES), and proprioceptive neuromuscular facilitation (PNF) on the visual perception of spatial neglect patients. [Subjects and Methods] The subjects were randomly allocated to 3 groups: an oculo-motor exercise (OME) group, a FES with oculo-motor exercise (FOME) group, and a PNF with oculo-motor exercise (POME) group. The line bisection test (LBT), motor free visual test (MVPT), and Catherine Bergego Scale (CBS) were used to measure visual perception. These were performed 5 times per week for 6 weeks. [Results] The OME group and POME group showed significant improvements according to the LBT and MVPT results, but the FOME group showed no significant improvement. According to the CBS, all 3 groups showed significant improvements. The OME and POME groups showed improvement over the FOME group in the LBT and MVPT. However, there was no significant difference among the three groups according to the CBS. [Conclusion] These results indicate that oculo-motor exercise and PNF with oculo-motor exercise had more positive effects than FES with oculo-motor exercise on the visual perception of spatial neglect patients. PMID:27190436
A long-standing difficulty in brain research has been to disentangle how information flows across circuits composed by multiple local and distant cerebral areas. At the large-scale level, several brain imaging methods have contributed to the understanding of those circuits by capturing the covariance or coupling patterns of blood oxygen level-dependent (BOLD) activity between distributed brain regions. The hypothesis is that underlying information processes are closely associated to synchronized brain activity, and therefore to the functional connectivity structure of the human brain. In this study, we have used a recently developed method called stepwise functional connectivity analysis. Our results show that motor and visual connectivity merge in a multimodal integration network that links together perception, action and cognition in the human functional connectome.
Hong, Wei-Hsien; Chen, Hseih-Ching; Shen, I-Hsuan; Chen, Chung-Yao; Chen, Chia-Ling; Chung, Chia-Ying
The aim of this study was to evaluate the relationships of muscle strength at different angular velocities and gross motor functions in ambulatory children with cerebral palsy (CP). This study included 33 ambulatory children with spastic CP aged 6-15 years and 15 children with normal development. Children with CP were categorized into level I (n=17) or level II (n=16) according to Gross Motor Function Classification System (GMFCS) levels. All children underwent curl-up test and isokinetic tests of the knee extensor and flexor muscle. Children with CP underwent the gross motor function assessments, including the Gross Motor Function Measure (GMFM-66) and the gross motor subtests of Bruininks-Oseretsky Test of Motor Proficiency (BOTMP). The hamstring-quadriceps ratio (HQ ratio) was calculated as 100%×(isokinetic peak torque of hamstring (knee flexor)/isokinetic peak torque of quadriceps (knee extensor)). Children with GMFCS level II had lower BOTMP and GMFM-66 scores, curl-up scores, HQ ratio, and knee muscle strength, especially knee flexor, compared to those with GMFCS level I. The regression analysis showed that knee flexor torques at 60 and 90°/s are mainly related to balance (r(2)=0.167, p=0.011) and strength (r(2)=0.243, p=0.002) while knee flexor torques at 120°/s mainly contribute to running speed and agility (r(2)=0.372, p<0.001). These findings suggest that children with CP had knee strength deficits, especially knee flexor. Postural muscle (knee flexor) strength dominated gross motor function than antigravity muscle strength (knee extensor). The knee flexor strength at different angular velocities was associated with various gross motor tasks. The HQ ratio may be used as a potential biomarker to probe the therapeutic effectiveness for muscle strengthening in these children. These data may allow clinician for formulating effective muscle strengthening strategies for these children.
Toschi, Nicola; Duggento, Andrea; Passamonti, Luca
The word 'e-motion' derives from the Latin word 'ex-moveo' which literally means 'moving away from something/somebody'. Emotions are thus fundamental to prime action and goal-directed behavior with obvious implications for individual's survival. However, the brain mechanisms underlying the interactions between emotional and motor cortical systems remain poorly understood. A recent diffusion tensor imaging study in humans has reported the existence of direct anatomical connections between the amygdala and sensory/(pre)motor cortices, corroborating an initial observation in animal research. Nevertheless, the functional significance of these amygdala-sensory/(pre)motor pathways remain uncertain. More specifically, it is currently unclear whether a distinct amygdala-sensory/(pre)motor circuit can be identified with resting-state functional magnetic resonance imaging (rs-fMRI). This is a key issue, as rs-fMRI offers an opportunity to simultaneously examine distinct neural circuits that underpin different cognitive, emotional and motor functions, while minimizing task-related performance confounds. We therefore tested the hypothesis that the amygdala and sensory/(pre)motor cortices could be identified as part of the same resting-state functional connectivity network. To this end, we examined independent component analysis results in a very large rs-fMRI data-set drawn from the Human Connectome Project (n = 820 participants, mean age: 28.5 years). To our knowledge, we report for the first time the existence of a distinct amygdala-sensory/(pre)motor functional network at rest. rs-fMRI studies are now warranted to examine potential abnormalities in this circuit in psychiatric and neurological diseases that may be associated with alterations in the amygdala-sensory/(pre)motor pathways (e.g. conversion disorders, impulse control disorders, amyotrophic lateral sclerosis and multiple sclerosis).
Goozee, Rhianna; O'Daly, Owen; Handley, Rowena; Reis Marques, Tiago; Taylor, Heather; McQueen, Grant; Hubbard, Kathryn; Pariante, Carmine; Mondelli, Valeria; Reinders, Antje A T S; Dazzan, Paola
The dopaminergic system plays a key role in motor function and motor abnormalities have been shown to be a specific feature of psychosis. Due to their dopaminergic action, antipsychotic drugs may be expected to modulate motor function, but the precise effects of these drugs on motor function remain unclear. We carried out a within-subject, double-blind, randomized study of the effects of aripiprazole, haloperidol and placebo on motor function in 20 healthy men. For each condition, motor performance on an auditory-paced task was investigated. We entered maps of neural activation into a random effects general linear regression model to investigate motor function main effects. Whole-brain imaging revealed a significant treatment effect in a distributed network encompassing posterior orbitofrontal/anterior insula cortices, and the inferior temporal and postcentral gyri. Post-hoc comparison of treatments showed neural activation after aripiprazole did not differ significantly from placebo in either voxel-wise or region of interest analyses, with the results above driven primarily by haloperidol. We also observed a simple main effect of haloperidol compared with placebo, with increased task-related recruitment of posterior cingulate and precentral gyri. Furthermore, region of interest analyses revealed greater activation following haloperidol compared with placebo in the precentral and post-central gyri, and the putamen. These diverse modifications in cortical motor activation may relate to the different pharmacological profiles of haloperidol and aripiprazole, although the specific mechanisms underlying these differences remain unclear. Evaluating healthy individuals can allow investigation of the effects of different antipsychotics on cortical activation, independently of either disease-related pathology or previous treatment. Hum Brain Mapp 38:1833-1845, 2017. © 2017 Wiley Periodicals, Inc.
Vernon, Natalia; Mohananey, Divyanshu; Ghetmiri, Ehsan; Ghaffari, Gisoo
Eosinophilic esophagitis (EoE) is a chronic inflammatory process characterized by symptoms of esophageal dysfunction and, histologically, by eosinophilic infiltration of the esophagus. In adults, it commonly presents with dysphagia, food impaction, and chest or abdominal pain. Chronic inflammation can lead to diffuse narrowing of the esophageal lumen which may cause food impaction. Endoscopic procedures to relieve food impaction may lead to complications such as esophageal perforation due to the friability of the esophageal mucosa. Spontaneous transmural esophageal rupture, also known as Boerhaave's syndrome, as a primary manifestation of EoE is rare. In this paper, we present two adult patients who presented with esophageal perforation as the initial manifestation of EoE. This rare complication of EoE has been documented in 13 other reports (11 adults, 2 children) and only 1 of the patients had been previously diagnosed with EoE. A history of dysphagia was present in 1 of our patients and in the majority of previously documented patients. Esophageal perforation is a potentially severe complication of EoE. Patients with a history of dysphagia and patients with spontaneous esophageal perforation should warrant an evaluation for EoE. PMID:24899902
Hasegawa, Atsushi; Takahashi, Masahito; Satomi, Kazuhiko; Ohne, Hideaki; Takeuchi, Takumi; Sato, Shunsuke; Ichimura, Shoichi
The aim of this study was to investigate forelimb motor function after cervical spinal cord injury in juvenile and adult rats. Both rats received a left segmental hemisection of the spinal cord after C3-C4 laminectomy. Behavioral evaluation of motor function was monitored and assessed using the New Rating Scale (NRS) and Forelimb Locomotor Scale (FLS) and by measuring the range of motion (ROM) of both the elbow and wrist. Complete left forelimb motor paralysis was observed in both rats. The NRS showed motor function recovery restored to 50.2 ± 24.7% in juvenile rats and 34.0 ± 19.8% in adult rats. FLS was 60.4 ± 26.8% in juvenile rats and 46.5 ± 26.9% in adult rats. ROM of the elbow and wrist were 88.9 ± 20.6% and 44.4 ± 24.1% in juvenile rats and 70.0 ± 29.2% and 40.0 ± 21.1% in adult rats. Thus, the NRS and ROM of the elbow showed a significant difference between age groups. These results indicate that left hemisection of the cervical spinal cord was not related to right-sided motor functions. Moreover, while motor paralysis of the left forelimb gradually recovered in both groups, the improvement was greater in juvenile rats.
Mathis, J G; Lehman, G A; Shanks, J C; Blom, E D; Brunelle, R L
Gastroesophageal reflux has been incriminated as a factor-inhibiting acquisition of esophageal speech after laryngectomy. Fourteen proficient esophageal speakers and 10 nonproficient speakers underwent esophageal manometry, esophageal pH probe testing, and Bernstein acid perfusion testing. Additionally, 175 laryngectomized members of Lost Chord Clubs answered mailed questionnaires about the frequency of reflux symptoms. Nonproficient and proficient esophageal speakers had a similar frequency of gastroesophageal reflux by pH probe testing, esophageal mucosal acid sensitivity by Bernstein testing, lower esophageal sphincter pressures, and gastroesophageal reflux symptoms. Gastroesophageal reflux does not appear to be a major factor in preventing esophageal speech.
Li, Meishan; Ogilvie, Hannah; Ochala, Julien; Artemenko, Konstantin; Iwamoto, Hiroyuki; Yagi, Naoto; Bergquist, Jonas; Larsson, Lars
Novel experimental methods, including a modified single fiber in vitro motility assay, X-ray diffraction experiments, and mass spectrometry analyses, have been performed to unravel the molecular events underlying the aging-related impairment in human skeletal muscle function at the motor protein level. The effects of old age on the function of specific myosin isoforms extracted from single human muscle fiber segments, demonstrated a significant slowing of motility speed (P < 0.001) in old age in both type I and IIa myosin heavy chain (MyHC) isoforms. The force-generating capacity of the type I and IIa MyHC isoforms was, on the other hand, not affected by old age. Similar effects were also observed when the myosin molecules extracted from muscle fibers were exposed to oxidative stress. X-ray diffraction experiments did not show any myofilament lattice spacing changes, but unraveled a more disordered filament organization in old age as shown by the greater widths of the 1, 0 equatorial reflections. Mass spectrometry (MS) analyses revealed eight age-specific myosin post-translational modifications (PTMs), in which two were located in the motor domain (carbonylation of Pro79 and Asn81) and six in the tail region (carbonylation of Asp900, Asp904, and Arg908; methylation of Glu1166; deamidation of Gln1164 and Asn1168). However, PTMs in the motor domain were only observed in the IIx MyHC isoform, suggesting PTMs in the rod region contributed to the observed disordering of myosin filaments and the slowing of motility speed. Hence, interventions that would specifically target these PTMs are warranted to reverse myosin dysfunction in old age.
Cunningham, David A.; Machado, Andre; Yue, Guang H.; Carey, Jim R.; Plow, Ela B.
The primary motor cortex (M1) possesses a functional somatotopic structure -representations of adjacent within-limb joints overlap to facilitate coordination while maintaining discrete centers for individuated movement. We examined whether similar organization exists across other sensorimotor cortices. Twenty-four right-handed healthy subjects underwent functional Magnetic Resonance Imaging (fMRI) while tracking complex targets with flexion/extension at right finger, elbow and ankle separately. Activation related to each joint at false discovery rate of .005 served as its representation across multiple regions. Within each region, we identified the Center of Mass (COM) for each representation, and overlap between representations of within-limb (finger and elbow) and between-limb joints (finger and ankle). Somatosensory (S1) and premotor cortices (PMC) demonstrated greater distinction of COM and minimal overlap for within- and between-limb representations. Contrarily, M1 and supplementary motor area (SMA) showed more integrative somatotopy with higher sharing for within-limb representations. Superior and inferior parietal lobule (SPL and IPL) possessed both types of structure. Some clusters exhibited extensive overlap of within- and between-limb representations, while others showed discrete COMs for within-limb representations. Our results help infer hierarchy in motor control. Areas as S1 may be associated with individuated movements, while M1 may be more integrative for coordinated motion; parietal associative regions may allow switch between both modes of control. Such hierarchy creates redundant opportunities to exploit in stroke rehabilitation. Use of complex rather than traditionally used simple movements was integral to illustrating comprehensive somatotopic structure; complex tasks can potentially help understand cortical representation of skill and learning-related plasticity. PMID:23920009
Sweetser, Seth; Busciglio, Irene A; Camilleri, Michael; Bharucha, Adil E; Szarka, Lawrence A; Papathanasopoulos, Athanasios; Burton, Duane D; Eckert, Deborah J; Zinsmeister, Alan R
Lubiprostone, a bicyclic fatty acid chloride channel activator, is efficacious in treatment of chronic constipation and constipation-predominant irritable bowel syndrome. The study aim was to compare effects of lubiprostone and placebo on colonic sensory and motor functions in humans. In double-blind, randomized fashion, 60 healthy adults received three oral doses of placebo or 24 microg lubiprostone per day in a parallel-group, placebo-controlled trial. A barostat-manometry tube was placed in the left colon by flexible sigmoidoscopy and fluoroscopy. We measured treatment effects on colonic sensation and motility with validated methods, with the following end points: colonic compliance, fasting and postprandial tone and motility indexes, pain thresholds, and sensory ratings to distensions. Among participants receiving lubiprostone or placebo, 26 of 30 and 28 of 30, respectively, completed the study. There were no overall effects of lubiprostone on compliance, fasting tone, motility indexes, or sensation. However, there was a treatment-by-sex interaction effect for compliance (P = 0.02), with lubiprostone inducing decreased fasting compliance in women (P = 0.06) and an overall decreased colonic tone contraction after a standard meal relative to fasting tone (P = 0.014), with greater effect in women (P < 0.01). Numerical differences of first sensation and pain thresholds (P = 0.11 in women) in the two groups were not significant. We concluded that oral lubiprostone 24 microg does not increase colonic motor function. The findings of decreased colonic compliance and decreased postprandial colonic tone in women suggest that motor effects are unlikely to cause accelerated colonic transit with lubiprostone, although they may facilitate laxation. Effects of lubiprostone on sensitivity deserve further study.
Esophageal voice obtained through logopedic treatment and speech produced by electronic prostheses is the principal means of verbal communication of laryngectomized patients. Several factors condition the success of logopedic rehabilitation: entity of hypopharyngeal surgical exeresis and scar repairing modalities; rehabilitation technique employed; patient's skill in controlling pharyngo-esophageal tract and articulation organs; patient motivation. A previous study executed by our School reported that only the 20% of the patients who did not practise logopedic therapy employed the laryngophone. Reduced use of electronic prosthesis depends on three factors: acoustic products of poor quality; evidence of anatomic and functional impairment pointed out by laryngophone use; limitation of manual activity during phonation. Electronic prostheses have a precise indication in the following cases: immediately after surgery; in case of logopedic treatment failure and when tracheo-esophageal prosthesis are contraindicated; when the esophageal voice has an insufficient volume or in noisy environments. Finally indicative criteria to introduce patients to the most suitable rehabilitation modality are reported.
Lacy, Brian E; Weiser, Kirsten
Symptoms of chest pain and dysphagia are common in the adult population. Most patients initially undergo an evaluation to exclude anatomic causes (ie, esophagitis, stricture) and cardiovascular disease as the etiology of these symptoms. Patients with persistent symptoms may then be referred for specialized testing of the esophagus, including esophageal manometry. Disorders of esophageal motility, which include achalasia, diffuse esophageal spasm, nutcracker esophagus, hypertensive lower esophageal sphincter, and ineffective motility are often identified in these patients. Unfortunately, the etiology of these disorders has not been well characterized and the treatment has not been standardized. This review will briefly discuss the impact, etiology, and diagnosis of esophageal motility disorders, and then focus on the medical management of these disorders using evidence from well-designed, prospective studies, where available.
Asaoka, Daisuke; Nagahara, Akihito; Hojo, Mariko; Matsumoto, Kenshi; Ueyama, Hiroya; Matsumoto, Kohei; Izumi, Kentaro; Takeda, Tsutomu; Komori, Hiroyuki; Akazawa, Yoichi; Shimada, Yuji; Osada, Taro; Watanabe, Sumio
The aim of the present study was to investigate the efficacy of a potassium-competitive acid blocker (PCAB) named vonoprazan (VPZ) for improving symptoms in patients with reflux esophagitis (RE), non-erosive reflux disease (NERD), and functional dyspepsia (FD). A hospital-based, retrospective study of outpatients in our department (Department of Gastroenterology, University of Juntendo, Tokyo, Japan) between March 2015 and August 2016 was performed. The patients who were experiencing heartburn, acid regurgitation, gastric pain, and/or a heavy feeling in the stomach of at least moderate severity at baseline were treated with 20 mg VPZ once daily for 4 weeks. The patients completed the global overall symptom (GOS) scale to determine their symptom severity at baseline and after the 4 week treatment period. The proportions of patients with RE, NERD, and FD achieving improvement of their symptoms, defined as a GOS scale score of 1 (‘no problem’) or 2 (‘minimal problem’), were evaluated. During 4 weeks of VPZ therapy, changes in the gastroesophageal reflux disease (GERD) score, which was defined as the total points for heartburn and acid regurgitation on the GOS scale in patients with RE and NERD, and in the FD score, which was defined as the total points for gastric pain and a heavy feeling in the stomach on the GOS scale in patients with FD, were also evaluated. A total of 88 eligible cases were included in the present study, comprising 20 patients with RE, 25 patients with NERD, and 43 patients with FD. The rates of symptomatic improvement in patients with RE, NERD, and FD were 75.0, 60.0, and 48.8%, respectively. For the patients who were first administered VPZ, the rates of symptomatic improvement were 90.9, 66.7, and 58.8% in patients with RE, NERD, and FD, respectively. For those patients who were resistant to 8 weeks of proton pump inhibitor therapy, the rates of symptomatic improvement were 55.6, 53.8, and 42.3% in patients with RE, NERD, and FD
Papageorgiou, T Dorina; Curtis, William A; McHenry, Monica; LaConte, Stephen M
This study examines the effects of neurofeedback provided by support vector machine (SVM) classification-based real-time functional magnetic resonance imaging (rt-fMRI) during two types of motor tasks. This approach also enables the examination of the neural regions associated with predicting mental states in different domains of motor control, which is critical to further our understanding of normal and impaired function. Healthy volunteers (n = 13) performed both a simple button tapping task, and a covert rate-of-speech counting task. The average prediction accuracy was approximately 95% for the button tapping task and 86% for the speech task. However, subsequent offline analysis revealed that classification of the initial runs was significantly lower - 75% (p<0.001) for button and 72% (p<0.005) for speech. To explore this effect, a group analysis was performed using the spatial maps derived from the SVM models, which showed significant differences between the two fMRI runs. One possible explanation for the difference in spatial patterns and the asymmetry in the prediction accuracies is that when subjects are actively engaged in the task (i.e. when they are trying to control a computer interface), they are generating stronger BOLD responses in terms of both intensity and spatial extent.
Dhaliwal, J; Tobias, V; Sugo, E; Varjavandi, V; Lemberg, D; Day, A; Bohane, T; Ledder, O; Jiwane, A; Adams, S; Henry, G; Dilley, A; Shi, E; Krishnan, U
Eosinophilic esophagitis (EoE) has only rarely been reported in esophageal atresia (EA) patients. A retrospective case analysis of all EA patients born at our center between January 1999 and April 2012 was performed. A total of 113 of patients were identified; 10 patients were excluded as a result of inadequate data. Eighteen patients (17%) were diagnosed with EoE. The average number of eosinophilis was 30/high-power field (HPF) (19/HPF-80/HPF). The median age for diagnosis of EoE was 1 year and 6 months (8 months-8 years and 7 months). Children with EoE had a significantly greater incidence of reflux symptoms, dysphagia, tracheomalacia, and 'hypoxic spells' (P < 0.05). EoE patients also underwent significantly more surgery including fundoplication and aortopexy when compared with those without EoE (P < 0.0001). Although the incidence of gastrostomy was greater in the EoE group (33% vs. 13%), this was not statistically significant. Half of the EoE patients had a coexisting atopic condition at time of diagnosis. The commonest condition was asthma 7/18 (38%) followed by specific food allergy 6/18 (33%). EoE was treated in 11 patients with either swallowed fluticasone or budesonide slurry. All improved clinically. Histologically, five had complete resolution and six had partial improvement. Six children with EoE were treated with acid suppression alone. All improved clinically, and 5/6 had subsequent histological resolution. One child who received acid suppression and an exclusion diet also improved. Seven patients (38%) had an esophageal stricture at time of EoE diagnosis. Five were dilated at time of the initial endoscopy, prior to the diagnosis of EoE being available. Two patients had resolution of their strictures on medical treatment of their EoE alone and did not require further dilatation. EoE was seen in 17% of children with EA in this study. EoE should be considered in EA patients with persistent symptoms on standard reflux treatment, increasing
Ding, Yuetong; Qu, Yibo; Feng, Jia; Wang, Meizhi; Han, Qi; So, Kwok-Fai; Wu, Wutian; Zhou, Libing
Brachial plexus injury (BPI) and experimental spinal root avulsion result in loss of motor function in the affected segments. After root avulsion, significant motoneuron function is restored by re-implantation of the avulsed root. How much this functional recovery depends on corticospinal inputs is not known. Here, we studied that question using Celsr3|Emx1 mice, in which the corticospinal tract (CST) is genetically absent. In adult mice, we tore off right C5–C7 motor and sensory roots and re-implanted the right C6 roots. Behavioral studies showed impaired recovery of elbow flexion in Celsr3|Emx1 mice compared to controls. Five months after surgery, a reduced number of small axons, and higher G-ratio of inner to outer diameter of myelin sheaths were observed in mutant versus control mice. At early stages post-surgery, mutant mice displayed lower expression of GAP-43 in spinal cord and of myelin basic protein (MBP) in peripheral nerves than control animals. After five months, mutant animals had atrophy of the right biceps brachii, with less newly formed neuromuscular junctions (NMJs) and reduced peak-to-peak amplitudes in electromyogram (EMG), than controls. However, quite unexpectedly, a higher motoneuron survival rate was found in mutant than in control mice. Thus, following root avulsion/re-implantation, the absence of the CST is probably an important reason to hamper axonal regeneration and remyelination, as well as target re-innervation and formation of new NMJ, resulting in lower functional recovery, while fostering motoneuron survival. These results indicate that manipulation of corticospinal transmission may help improve functional recovery following BPI. PMID:25003601
He, Hui; Luo, Cheng; Chang, Xin; Shan, Yan; Cao, Weifang; Gong, Jinnan; Klugah-Brown, Benjamin; Bobes, Maria A; Biswal, Bharat; Yao, Dezhong
Healthy aging is typically accompanied by a decrease in the motor capacity. Although the disrupted neural representations and performance of movement have been observed in older age in previous studies, the relationship between the functional integration of sensory-motor (SM) system and aging could be further investigated. In this study, we examine the impact of healthy aging on the resting-state functional connectivity (rsFC) of the SM system, and investigate as to how aging is affecting the rsFC in SM network. The SM network was identified and evaluated in 52 healthy older adults and 51 younger adults using two common data analytic approaches: independent component analysis and seed-based functional connectivity (seed at bilateral M1 and S1). We then evaluated whether the altered rsFC of the SM network could delineate trajectories of the age of older adults using a machine learning methodology. Compared with the younger adults, the older demonstrated reduced functional integration with increasing age in the mid-posterior insula of SM network and increased rsFC among the sensorimotor cortex. Moreover, the reduction in the rsFC of mid-posterior insula is associated with the age of older adults. Critically, the analysis based on two-aspect connectivity-based prediction frameworks revealed that the age of older adults could be reliably predicted by this reduced rsFC. These findings further indicated that healthy aging has a marked influence on the SM system that would be associated with a reorganization of SM system with aging. Our findings provide further insight into changes in sensorimotor function in the aging brain.
He, Hui; Luo, Cheng; Chang, Xin; Shan, Yan; Cao, Weifang; Gong, Jinnan; Klugah-Brown, Benjamin; Bobes, Maria A.; Biswal, Bharat; Yao, Dezhong
Healthy aging is typically accompanied by a decrease in the motor capacity. Although the disrupted neural representations and performance of movement have been observed in older age in previous studies, the relationship between the functional integration of sensory-motor (SM) system and aging could be further investigated. In this study, we examine the impact of healthy aging on the resting-state functional connectivity (rsFC) of the SM system, and investigate as to how aging is affecting the rsFC in SM network. The SM network was identified and evaluated in 52 healthy older adults and 51 younger adults using two common data analytic approaches: independent component analysis and seed-based functional connectivity (seed at bilateral M1 and S1). We then evaluated whether the altered rsFC of the SM network could delineate trajectories of the age of older adults using a machine learning methodology. Compared with the younger adults, the older demonstrated reduced functional integration with increasing age in the mid-posterior insula of SM network and increased rsFC among the sensorimotor cortex. Moreover, the reduction in the rsFC of mid-posterior insula is associated with the age of older adults. Critically, the analysis based on two-aspect connectivity-based prediction frameworks revealed that the age of older adults could be reliably predicted by this reduced rsFC. These findings further indicated that healthy aging has a marked influence on the SM system that would be associated with a reorganization of SM system with aging. Our findings provide further insight into changes in sensorimotor function in the aging brain. PMID:28111548
Lakhani, Bimal; Hayward, Kathryn S; Boyd, Lara A
The relationships between impairment, function, arm use and underlying brain structure following stroke remain unclear. Although diffusion weighted imaging is useful in broadly assessing white matter structure, it has limited utility in identifying specific underlying neurobiological components, such as myelin. The purpose of the present study was to explore relationships between myelination and impairment, function and activity in individuals with chronic stroke. Assessments of paretic upper-extremity impairment and function were administered, and 72-hour accelerometer based activity monitoring was conducted on 19 individuals with chronic stroke. Participants completed a magnetic resonance imaging protocol that included a high resolution T1 anatomical scan and a multi-component T2 relaxation imaging scan to quantify myelin water fraction (MWF). MWF was automatically parcellated from pre- and post-central subcortical regions of interest and quantified as an asymmetry ratio (contralesional/ipsilesional). Cluster analysis was used to group more and less impaired individuals based on Fugl-Meyer upper extremity scores. A significantly higher precentral MWF asymmetry ratio was found in the more impaired group compared to the less impaired group (p < 0.001). There were no relationships between MWF asymmetry ratio and upper-limb use. Stepwise multiple linear regression identified precentral MWF asymmetry as the only variable to significantly predict impairment and motor function in the upper extremity (UE). These results suggest that asymmetric myelination in a motor specific brain area is a significant predictor of upper-extremity impairment and function in individuals with chronic stroke. As such, myelination may be utilized as a more specific marker of the neurobiological changes that predict long term impairment and recovery from stroke.
The course of acquisition of various gross motor skills and changes in their patterns with advancing age, in addition to joint contracture, hand function, and mental ability, were investigated in 20 non-ambulatory children with spastic diplegia and periventricular leukomalacia. Among the diplegic children studied, those with lower locomotive ability also had lower hand function, lower mental ability and slower acquisition of gross motor skills. All subjects could roll by 24 months of age. Fourteen patients could creep by 18 months of age, and the remaining six by 30 months. Crawling was observed in only five patients with mild locomotive disability as a final locomotive pattern on the floor. Among ten patients with mild locomotive disability, three could sit by 2 years of age, six by 3 years, and one by 4 years. Among ten patients with severe disability, two, two, four and two children could sit at the ages of 2, 3, 4 and 5 years, respectively. Twelve patients could walk with support at between 2 and 5 years of age. Delay in acquisition of creeping or sitting differed somewhat among subjects with similar final locomotive disability. The majority of subjects with severe locomotive disability developed contracture of the hips and knees. Only two patients with mild disability had contracture of the ankles.
Otten, Paul; Kim, Jonghyun; Son, Sang Hyuk
Standard upper-limb motor function impairment assessments, such as the Fugl-Meyer Assessment (FMA), are a critical aspect of rehabilitation after neurological disorders. These assessments typically take a long time (about 30 min for the FMA) for a clinician to perform on a patient, which is a severe burden in a clinical environment. In this paper, we propose a framework for automating upper-limb motor assessments that uses low-cost sensors to collect movement data. The sensor data is then processed through a machine learning algorithm to determine a score for a patient’s upper-limb functionality. To demonstrate the feasibility of the proposed approach, we implemented a system based on the proposed framework that can automate most of the FMA. Our experiment shows that the system provides similar FMA scores to clinician scores, and reduces the time spent evaluating each patient by 82%. Moreover, the proposed framework can be used to implement customized tests or tests specified in other existing standard assessment methods. PMID:26287206
Gurbuz, Nigar; Afsar, Sevgi Ikbali; Ayaş, Sehri; Cosar, Sacide Nur Saracgil
[Purpose] This study aimed to evaluate the effectiveness of mirror therapy combined with a conventional rehabilitation program on upper extremity motor and functional recovery in stroke patients. [Subjects and Methods] Thirty-one hemiplegic patients were included. The patients were randomly assigned to a mirror (n=16) or conventional group (n=15). The patients in both groups underwent conventional therapy for 4 weeks (60-120 minutes/day, 5 days/week). The mirror group received mirror therapy, consisting of periodic flexion and extension movements of the wrist and fingers on the non-paralyzed side. The patients in the conventional group performed the same exercises against the non-reflecting face of the mirror. The patients were evaluated at the beginning and end of the treatment by a blinded assessor using the Brunnstrom stage, Fugl-Meyer Assessment (FMA) upper extremity score, and the Functional Independence Measure (FIM) self-care score. [Results] There was an improvement in Brunnstrom stage and the FIM self-care score in both groups, but the post-treatment FMA score was significantly higher in the mirror therapy group than in the conventional treatment group. [Conclusion] Mirror therapy in addition to a conventional rehabilitation program was found to provide additional benefit in motor recovery of the upper extremity in stroke patients.
Agostini, Michela; Moja, Lorenzo; Banzi, Rita; Pistotti, Vanna; Tonin, Paolo; Venneri, Annalena; Turolla, Andrea
Recent advances in telecommunication technologies have boosted the possibility to deliver rehabilitation via the internet (i.e. telerehabilitation). Several studies have shown that telerehabilitation is effective to improve clinical outcomes in disabling conditions. The aim of this review was to determine whether telerehabilitation was more effective than other modes of delivering rehabilitation to regain motor function, in different populations of patients.We searched PubMed, Embase and the Cochrane library retrieving 2360 records. Twelve studies were included involving different populations (i.e. neurological, total knee arthroplasty (TKA), cardiac) of patients. Inconclusive finding were found on the effect of telerehabilitation for neurological patients (SMD = 0.08, CI 95% = -0.13, 0.29), while both for cardiac (SMD = 0.24, CI 95% = 0.04, 0.43) and TKA patients (Timed Up and Go test: MD = -5.17, CI 95% = -9.79, -0.55) the results were in favour of telerehabilitation.Con