Abnormal Motor Activity Research Articles

Investigating the association between symptoms and functional activity in brain regions in schizophrenia: A cross-sectional fmri-based neuroimaging study

Schizophrenia is a persistent neurological disorder profoundly affecting cognitive, emotional, and behavioral functions, prominently characterized by delusions, hallucinations, disordered speech, and abnormal motor activity. These symptoms often present diagnostic challenges due to their overlap with other forms of psychosis. Therefore, the implementation of automated diagnostic methodologies is imperative. This research leverages Functional Magnetic Resonance Imaging (fMRI), a neuroimaging modality capable of delineating functional activations across diverse brain regions. Furthermore, the utilization of evolving machine learning techniques for fMRI data analysis has significantly progressive. Here, our study stands as a novel attempt, focusing on the comprehensive assessment of both classical and atypical symptoms of schizophrenia. We aim to uncover associated changes in brain functional activity. Our study encompasses two distinct fMRI datasets (1.5T and 3T), each comprising 34 schizophrenia patients for the 1.5T dataset and 25 schizophrenia patients for the 3T dataset, along with an equal number of healthy controls. Machine learning algorithms are applied to assess data subsets, enabling an in-depth evaluation of the current functional condition concerning symptom impact. The identified voxels contribute to determining the brain regions most influenced by each symptom, as quantified by symptom intensity. This rigorous approach has yielded various new findings while maintaining an impressive classification accuracy rate of 97 %. By elucidating variations in activation patterns across multiple brain regions in individuals with schizophrenia, this study contributes to the understanding of functional brain changes associated with the disorder. The insights gained may inform differential clinical interventions and provide a means of assessing symptom severity accurately, offering new avenues for the management of schizophrenia.

Alterations of sleep initiation in NREM parasomnia after sleep deprivation – A multimodal pilot study

ObjectivesNREM parasomnias also known as disorders of arousal (DOA) are characterised by abnormal motor and autonomic activation during arousals primarily from slow wave sleep. Dissociative state between sleep and wake is likely responsible for clinical symptoms of DOA. We therefore investigated potential dissociation outside of parasomnic events by using simultaneous 256-channel EEG (hdEEG) and functional magnetic resonance imaging (fMRI). MethodsEight DOA patients (3 women, mean age = 27.8; SD = 4.2) and 8 gender and age matched healthy volunteers (3 women, mean age = 26,5; SD = 4.0) were included into the study. They underwent 30–32 h of sleep deprivation followed by hdEEG and fMRI recording. We determined 2 conditions: falling asleep (FA) and arousal (A), that occurred outside of deep sleep and/or parasomnic event. We used multimodal approach using data obtained from EEG, fMRI and EEG-fMRI integration approach. ResultsDOA patients showed increase in delta and beta activity over postcentral gyrus and cuneus during awakening period. This group expressed increased connectivity between motor cortex and cingulate during arousals unrelated to parasomnic events in the beta frequency band. They also showed lower connectivity between different portions of cingulum. In contrast, the greater connectivity was found between thalamus and some cortical areas, such as occipital cortex. ConclusionOur findings suggest a complex alteration in falling asleep and arousal mechanisms at both subcortical and cortical levels in response to sleep deprivation. As this alteration is present also outside of slow wave sleep and/or parasomnic episodes we believe this could be a trait factor of DOA.

EFFECT OF KARMA BASTI AND SHIRODHARA IN GRAHANI (irritable bowel syndrome)

Irritable bowel syndrome (IBS) is a gastrointestinal disorder having a group of symptoms including abdominal pain and changes in the pattern of bowel movements without any evidence of underlying damage. The pathogenesis of IBS is not fully understood, although roles for abnormal gut motor and sensory activity, central neural dysfunction, psychological disturbances, stress and luminal factors have been proposed. About 10-15% of the people in the developed world are believed to be affected by IBS, it is estimated that 45% of people globally are affected by IBS. In Ayurveda, IBS can be correlated to Grahani Roga due to their clinical presentation. In this case an effort has been made to treat patients having symptoms of Muhurbaddha Muhurdravam (episode of difficult evacuation of bowel and loose stools), Udarashool (pain in abdomen) and Apakwa Malapravritti (sticky stool with mucus). Male Patient XYZ of age 54years treated with various Panchakarma procedures like Basti (herbal medicated enema), Taila Shirodhara (pouring Herbal medicated oil on head) and oral medications. At the end of 50 days of treatment (Kala basti-16days+ oral medication-34days) patient got significant improvement in the sign and symptoms of disease.

Restless sleep disorder in children with epileptic and non-epileptic nocturnal attacks.

Restless sleep disorder (RSD) is an important sleep disorder characterised by the presence of frequent large muscle movements (LMM) during sleep, which may be comorbid to other conditions/diseases. In this study, we investigated the frequency and the characteristics of RSD among children who were evaluated by polysomnography (PSG) due to epileptic and non-epileptic nocturnal attacks. We analysed consecutively children younger than 18 years who were referred for PSG recording due to abnormal motor activities during sleep. The diagnosis of nocturnal events as sleep-related epilepsy was made based on the current consensus. Patients who were referred with suspicion of sleep-related epilepsy, but who were diagnosed to have non-epileptic nocturnal events and children with a definitive diagnosis of NREM sleep parasomnias were also enrolled. Sixty-two children were analysed in this study (17 children with sleep-related epilepsy, 20 children with NREM parasomnia, and 25 children with nocturnal events not otherwise classified [neNOS]). The mean number of LMM, LMM index, LMM-associated with arousal and its index were all significantly higher in children with sleep-related epilepsy. Restless sleep disorder was present in 47.1% of patients with epilepsy, 25% of patients with parasomnia, and in 20% of patients with neNOS. The mean A3 duration and the A3 index were higher in children with sleep-related epilepsy and RSD compared with those with parasomnia and restless sleep disorder. Patients with RSD had lower ferritin levels than those without RSD in all subgroups. Our study demonstrates a high prevalence of restless sleep disorder in children with sleep-related epilepsy, associated with an increased cyclic alternating pattern.

CNS-dominant human FMRP isoform rescues seizures, fear, and sleep abnormalities in Fmr1-KO mice.

Fragile X syndrome is a neurodevelopmental disorder caused by the absence of the mRNA-binding protein fragile X messenger ribonucleoprotein (FMRP). Because FMRP is a highly pleiotropic protein controlling the expression of hundreds of genes, viral vector-mediated gene replacement therapy is viewed as a potential viable treatment to correct the fundamental underlying molecular pathology inherent in the disorder. Here, we studied the safety profile and therapeutic effects of a clinically relevant dose of a self-complementary adeno-associated viral (AAV) vector containing a major human brain isoform of FMRP after intrathecal injection into wild-type and fragile X-KO mice. Analysis of the cellular transduction in the brain indicated primarily neuronal transduction with relatively sparse glial expression, similar to endogenous FMRP expression in untreated wild-type mice. AAV vector-treated KO mice showed recovery from epileptic seizures, normalization of fear conditioning, reversal of slow-wave deficits as measured via electroencephalographic recordings, and restoration of abnormal circadian motor activity and sleep. Further assessment of vector efficacy by tracking and analyzing individual responses demonstrated correlations between the level and distribution of brain transduction and drug response. These preclinical findings further demonstrate the validity of AAV vector-mediated gene therapy for treating the most common genetic cause of cognitive impairment and autism in children.

Locomotion Outcome Improvement in Mice with Glioblastoma Multiforme after Treatment with Anastrozole

Glioblastoma Multiforme (GBM) is a tumor that infiltrates several brain structures. GBM is associated with abnormal motor activities resulting in impaired mobility, producing a loss of functional motor independence. We used a GBM xenograft implanted in the striatum to analyze the changes in Y (vertical) and X (horizontal) axis displacement of the metatarsus, ankle, and knee. We analyzed the steps dissimilarity factor between control and GBM mice with and without anastrozole. The body weight of the untreated animals decreased compared to treated mice. Anastrozole reduced the malignant cells and decreased GPR30 and ERα receptor expression. In addition, we observed a partial recovery in metatarsus and knee joint displacement (dissimilarity factor). The vertical axis displacement of the GBM+anastrozole group showed a difference in the right metatarsus, right knee, and left ankle compared to the GBM group. In the horizontal axis displacement of the right metatarsus, ankle, and knee, the GBM+anastrozole group exhibited a difference at the last third of the step cycle compared to the GBM group. Thus, anastrozole partially modified joint displacement. The dissimilarity factor and the vertical and horizontal displacements study will be of interest in GBM patients with locomotion alterations. Hindlimb displacement and gait locomotion analysis could be a valuable methodological tool in experimental and clinical studies to help diagnose locomotive deficits related to GBM.

Probing motor dynamics at the muscle level-Acoustic myography in Parkinson's disease.

Acoustic myography (AMG) noninvasively probes muscle activity. We explored whether AMG captures abnormal motor activity in patients with Parkinson's disease (PD) and how this activity is modulated by antiparkinsonian medication. Twenty patients with PD underwent AMG of the biceps, triceps, extensor carpi radialis longus, and adductor policis muscles of the more affected arm during active and passive movements, using a mobile AMG device (CURO, Denmark). AMG and assessment of motor symptoms were performed in a pragmatic off-medication state, as well as one and 3 h after oral intake of 200 mg levodopa. Three AMG parameters were calculated using the CURO analysis system. Motor efficiency was expressed by the E-score, muscle fiber recruitment by the temporal T-score, spatial summation by the S-score, and S/T ratio. Twenty age- and sex-matched healthy subjects served as controls. Group mean values were statistically compared using unpaired two-tailed adjusted t-test and ANOVA with Tukey´s correction for multiple comparison (p≤ 0.05). For the biceps and extensor carpi radialis longus muscles, the active movement S:T ratio was lower in PD relative to healthy controls. The E-score was also lower during active and passive flexion/extension movements in the off-medication state. No significant between-group differences in the AMG scores were noted for the triceps muscle during active or passive movements. The active S:T ratio and the E-score during active elbow flexion and extension may offer a useful means to quickly assess abnormal motor activity and the effect of drug treatment in PD.

Aggressive behavior of patients with vascular dementia

There is a worldwide trend towards an increase in the number of people aged over 60, which in turn leads to an increase in the prevalence of vascular dementia and neuropsychiatric disorders, including the accompanying aggressive behavior. The authors analyze the relationship of neuropsychiatric symptoms with aggressive behavior and assess the impact of the evolution of dementia, socio-demographic factors on the development of aggressive behavior in some subtypes of vascular dementia based on literature data retrieved from Scopus, PubMed, eLibrary databases as well as national guidelines. Analyzing the publication was made by the method of the system analysis and generalization. The analysis of the literature suggests that aggressive behavior in patients with vascular dementia changes their lifestyle and worsens its quality, in addition, it increases the burden on caregivers. Also, this psychopathological process is one of the reasons for frequent hospitalizations of patients in psychiatric hospitals and social institutions, which becomes an urgent economic and medical problem at the state level. Of all the psychopathological symptoms in the clinical picture of vascular dementia, aggressive behavior periodically occurs together with apathy, depression, anxiety, abnormal motor activity and hallucinations. The question of the highest frequency of occurrence of aggressive tendencies in one or another subtype of vascular dementia remains debatable. Research on the relationship between dementia severity, gender, and aggressive behavior has been mixed. The question of the influence of the level of education on the manifestation of aggression in patients with vascular dementia remains completely unexplored. Thus, the above facts dictate the need for further study of these issues.

Evaluation of Chronic Constipation in Children With Autism Spectrum Disorder.

Chronic constipation occurs frequently in children with autism spectrum disorder (ASD). The primary objective was to determine whether chronic constipation is associated with a higher rate of abnormal colonic motor activity in ASD children than in non-ASD children. A secondary goal was to determine if clinical variables could identify children with ASD at risk for possessing abnormal colonic motility. A retrospective, propensity-matched, case-control study compared colonic manometry (CM) of an ASD cohort and non-ASD controls with chronic constipation. Clinical variables were evaluated as potential predictors for abnormal colonic motility. Fifty-six patients with ASD and 123 controls without the diagnosis of ASD who underwent CM were included. Propensity score resulted in 35 matched cohorts of ASD and controls. The rate of abnormal CM findings between ASD and matched controls (24% vs 20%, P = 0.78) did not differ significantly. A prediction model of abnormal CM that included ASD diagnosis, duration of constipation, and soiling achieved a sensitivity of 0.94 and specificity of 0.65. The risk for abnormal colonic motility increased 11% for every 1-year increase in duration of constipation. Odds for abnormal motility were 30 times higher in ASD children with soiling than controls with soiling (P < 0.0001). Chronic constipation does not appear to be associated with a higher rate of abnormal colonic motility in children with ASD. Clinical information of disease duration and presence of soiling due to constipation show promise in identifying patients with ASD at a greater risk for abnormal colonic motility.

TO STUDY CLINICAL PRESENTATION AND TIME OF ONSET OF SEIZURE IN TERM AND PRETERM NEONATES AND THE BIOCHEMICALABNORMALITY IN SEIZURES IN TERM AND PRETERM NEONATES.

INTRODUCTION: Seizure is dened as paroxysmal involuntary disturbance of brain function. It may manifest as impairment or loss of consciousness, abnormal motor activity, behavioural abnormality, sensory disturbance or autonomic dysfunction. Any abnormal, repetitive and stereotypic behaviour in neonates should be evaluated as possible seizure. Neonatal seizures is a common neurological problem with a frequency range from 0.95 to 3.5/1000 live births. AIMS &amp; OBJECTIVES:To assess the importance of biochemical abnormalities in neonatal seizures and to evaluate clinical presentation &amp; time of onset of seizures in term and preterm neonates. MATERIAL &amp; METHODS: A total of 90 neonates presenting with seizures admitted to NICU of National Institute of Medical Sciences &amp; Research, Jaipur from conducted from 1st January 2019 till 30 th June 2020 were enrolled in the study. Detailed antenatal, natal, postnatal history along with detailed examination was done. Baseline characteristics of convulsing neonate including sex, gestational age, birth weight, head circumference &amp; length were recorded at admission. Clinical details of each seizure episode reported by the mother and subsequently observed by the resident doctors on duty were recorded i.e. age at onset of seizures, duration of seizure, number and type of seizure. Relevant investigations including biochemical parameters were done immediately after baby had seizures and before instituting any specic treatment. Etiology of neonatal seizures and associated biochemical abnormalities were diagnosed. RESULTS: In the present study, out of 90 neonates studied, 64 were full term of which 49(76.5%) were AGAand 15(23.5%) were SGA, whereas 26 cases were preterm. The male: female ratio is 1.3:1. Most neonatal seizures occur in rst 3 days of life, i.e. 60 %. Most of them occurred on rst day of life (34%). Birth asphyxia was the cause of neonatal seizures in 82 % neonates who developed seizures on day-1 of life. Birth asphyxia and septicemia are common cause of neonatal seizures in our study, followed by pure metabolic disturbances 20 %. In pure metabolic seizures, hypoglycemia (47.8%) is most common more in preterm babies (55%) followed by hypocalcemia. In cases of non- metabolic seizures, which showed associated biochemical abnormalities, hypoglycemia was most common abnormality 24 of 52 cases (46.15%). 12 cases (52.1%) are associated with birth asphyxia and 11 cases (47.9%) are associated with septicemia. CONCLUSION: Biochemical abnormalities are common in neonatal seizures and often go unrecognized. These abnormalities may signicantly contribute to seizure activity correction of these abnormalities may play a signicant role in seizure control. Hence, a biochemical work up is necessary for all cases of neonatal seizures.

Pediatric Methamphetamine Toxicity: Clinical Manifestations and Therapeutic Use of Antipsychotics-One Institution's Experience.

Methamphetamine toxicity is common in the Southwestregion of the UnitedStates and presents diagnostic and treatment challenges in the pediatric population. The aim of our study was to characterize signs and symptoms of methamphetamine toxicity in pediatric patients, highlighting manifestations unique to this population. Additionally, our study sought to evaluate treatment modalities, specifically antipsychotics, in this population with the intent to characterize their adverse effects. This is a retrospective review ofpediatric patients (age > 2months ≤ 18years) at a tertiary care pediatric hospital with ICD-9 or ICD-10 codes suggestive of stimulant exposure between September 1, 2010, and July 31, 2017. Patients with clinical manifestations of sympathomimetic toxicity and confirmation of methamphetamine on urine drug testing via GC/MS were included. Nature, source, and route of exposure along with clinical manifestations including signs, complications, treatments utilized, and adverse events related to treatment were recorded. Specifically, adverse effects following administration of antipsychotics were studied. Seventy-nine patientsmet inclusion criteria: median age 2.0years. Typical manifestations of sympathomimetic toxicitywere common, including tachycardia (93.4%), hypertension (85.7%), agitation (79.7%), and abnormal motor activity (55.8%). The prominence of gastrointestinal signs (26.3%) and unique abnormal motor activity were notable. The most common treatments were intravenous fluids (96.1%) and benzodiazepines (77.9%). Antipsychotics were administered in 40.5% of cases, with haloperidol used in the majority. No patients developed seizures, dystonia, torsades de pointes, or hyperthermia after antipsychotic administration. Pediatric patients with methamphetamine toxicity commonlymanifest sympathomimetic signs.Antipsychoticswere often used as an adjunct treatment in this cohort of patients, and no adverse events were reported. Clinicians should be aware of prominent gastrointestinal signs and abnormal motor activity and neurologic manifestations unique to pediatric patients that will assist in making the correct diagnosis in cases of suspected methamphetamine toxicity.

Behavioral manifestations during REM sleep in idiopathic REM sleep behavior disorder

Introduction: Abnormal motor activity in rapid eye movement (REM) sleep is a major video-polysomnographic feature of idiopathic REM sleep behavior disorder (iRBD), which is considered as prodromal stage of synucleinopathies. The diagnosis is based on complex movements visible at the video recording during video-PSG, but more discreet motor manifestations can be observed as well. The aim was to perform a systematic video analysis of motor events in REM sleep.

The Correlation Between Children Who Use Bottle Feeding Ages 4 - 6 Years Against The Malocclusion

ABSTRACT&#x0D; Background: The prevalence of malocclusion in Indonesia is still very high at around 80% of the population and is one of the major dental and oral health problems, this is coupled with a low level of dental care awareness. The prevalence of malocclusion because of the habit of drinking milk with bottle feedings was 49.5% of 377 children. This is habit because, the habit of drinking milk with a bottle feeding causes the movement of the baby's tongue like a sucking motion. This abnormal tongue motor activity will result in aberrant swallowing habits which will eventually cause malocclusion. Purpose: To determine the correlation between children using bottle feeding aged 4 - 6 years to the occurrence of malocclusion. Methods: This study uses the Analytical Observational method with a cross sectional study design. The sample consisted of 30 children aged 4 - 6 years who met the criteria of the study determined by filling out questionnaires and intra-oral examination of samples Result: The result of Spearman's correlation statistical test, obtained the correlation coefficient value (r=0.435) which shows a moderate correlation. The results of the linear regression test to see if there are long-term effects of using a bottle feeding on the occurrence of malocclusion, obtained a value (p &lt;0.05) which shows a significant effect. Conclusion: There is a moderate correlation between children who use bottle feedings aged 4-6 years to malocclusion. The longer children use bottle feeding, the more severe the malocclusion of children.&#x0D; Keywords: Malocclusion, Bottle feeding

0003 LGI1 and CASPR2 Autoimmunity: Sleep Symptoms, Polysomnography, and Quantitative REM Sleep without Atonia

Abstract Introduction Sleep disturbances, including rapid eye movement (REM) behavior disorder (RBD), are known manifestations of voltage-gated-potassium-channel-complex VGKC-IgG seropositivity (VGKC+). Discovery of leucine-rich, glioma inactivated protein 1 (LGI1) and contactin-associated protein 2 (CASPR2) have refined our understanding of VGKC+. VGKC+ without LGI1/CASPR2-IgG (“double-negative”) has lost its clinical significance. Previous detailed sleep analysis of these subtypes has been limited. Methods We performed a retrospective study to characterize clinical and polysomnographic features of LGI1/CASPR2 seropositive (LGI1+/CASPR2+) and VGKC double-negative patients, including quantitative REM sleep without atonia (RSWA). Quantified RSWA was compared to matched controls and normative RSWA percentiles. Results Eleven LGI1+/CASPR2+ (LGI1+, 9) and twelve VGKC double-negative patients were analyzed. Insomnia was seen in 55% of LGI1+/CASPR2+ and 8% of VGKC double-negative patients (p=0.05). The LGI1+/CASPR2+ group had reduced slow wave sleep compared to the VGKC double-negative group. Five LGI1+ patients had clinical dream enactment behavior (DEB). Eight LGI1+ patients met quantitative diagnostic levels of RSWA. Higher RSWA levels were seen in the LGI1+/CASPR2+ group. Ten LGI1+/CASPR2+ patients received immunotherapy; all ten neurologically benefited with sleep benefits in 6/10. Conclusion Sleep disorders such as insomnia and RBD are part of the LGI1/CASPR2 autoimmune phenotype. Objective sleep manifestations can be seen on polysomnogram in the form of reduced N3 and elevated RSWA as compared to controls. Quantitative RSWA analysis identified RBD in more LGI1+ patients than clinical report or qualitative RSWA. In this study, RBD was only seen with LGI1+, not CASPR2+. The intermediate RSWA levels of the VGKC double-negative patients may suggest a spectrum of abnormal motor activity in these related antibodies. Additional studies are needed to further explore the biomarker potential of quantitative RSWA in autoimmune neurological conditions. Support This project was supported by the National Center forResearch Resources, National Institutes of Health, through Grant Number 1 UL1 RR024150- 01.

Characterization of the sleep disorder of anti-IgLON5 disease.

To characterize the sleep disorder of anti-IgLON5 disease. We reviewed 27 video-polysomnographies (V-PSG), 6 multiple sleep latency tests (MSLT), 2 videsomnoscopies with dexmedetomidine, and 10 actigraphies recorded during the disease course of five patients. Due to severe sleep architecture abnormalities, we used a novel modified sleep scoring system combining conventional stages with a descriptive approach in which two additional stages were identified: undifferentiated-NREM (UN-NREM) and poorly structured N2 (P-SN2) sleep that were characterized by abnormal motor activation and absence or sparse elements of conventional NREM sleep. Sleep-related vocalizations, movements, behaviors, and respiratory abnormalities were reported by bed-partners. In all patients, NREM sleep onset and sleep reentering after an awakening occurred as UN-NREM (median: 29.8% of total sleep time [TST]) and P-SN2 sleep (14.5% TST) associated with vocalizations and simple and quasi-purposeful movements. Sleep initiation was normalized in one patient with a high dose of steroids, but NREM sleep abnormalities reappeared in subsequent V-PSG. In all patients, if sleep continued uninterrupted, there was a progressive normalization with normal N2 (11.7% TST) and N3 (22.3% TST) sleep but stridor and obstructive apnea emerged. REM sleep behavior disorder (RBD) occurred in four patients. Sleep initiation was also altered in MSLT and dexmedetomidine-induced sleep. Actigraphy showed a 10-fold increase of nocturnal activity compared with controls. Sleep abnormalities remained stable during the disease. The sleep disorder of anti-IgLON5 disease presents as a complex sleep pattern characterized by abnormal sleep initiation with undifferentiated NREM sleep, RBD, periods of normal NREM sleep, stridor, and obstructive apnea.

Abnormal absorptive colonic motor activity in germ-free mice is rectified by butyrate, an effect possibly mediated by mucosal serotonin.

The role of short-chain fatty acids (SCFAs) in the control of colonic motility is controversial. Germ-free (GF) mice are unable to produce these metabolites and serve as a model to study how their absence affects colonic motility. GF transit is slower than controls, and colonization of these mice improves transit and serotonin [5-hydroxytryptamine (5-HT)] levels. Our aim was to determine the role SCFAs play in improving transit and whether this is dependent on mucosal 5-HT signaling. Motility was assessed in GF mice via spatiotemporal mapping. First, motor patterns in the whole colon were measured ex vivo with or without luminal SCFA, and outflow from the colon was recorded to quantify outflow caused by individual propulsive contractions. Second, artificial fecal pellet propulsion was measured. Motility was then assessed in tryptophan hydroxylase-1 (TPH1) knockout (KO) mice, devoid of mucosal 5-HT, with phosphate buffer, butyrate, or propionate intraluminal perfusion. GF mice exhibited a lower proportion of propulsive contractions, lower volume of outflow/contraction, slower velocity of contractions, and slower propulsion of fecal pellets compared with controls. SCFAs changed motility patterns to that of controls in all parameters. Butyrate administration increased the proportion of propulsive contractions in controls yet failed to in TPH1 KO mice. Propionate inhibited propulsive contractions in all mice. Our results reveal significant abnormalities in the propulsive nature of colonic motor patterns in GF mice, explaining the decreased transit time in in vivo studies. We show that butyrate but not propionate activates propulsive motility and that this may require mucosal 5-HT. NEW & NOTEWORTHY Understanding the role that the microbiota play in governing the physiology of colonic motility is lacking. Here, we offer for the first time, to our knowledge, a detailed analysis of colonic motor patterns and pellet propulsion using spatiotemporal mapping in the absence of microbiota. We show a striking difference in germ-free and control phenotypes and attribute this to a lack of fermentation-produced short-chain fatty acid. We then show that butyrate but not propionate can restore motility and that the butyrate effect likely requires mucosal 5-hydroxytryptamine.

A single-center audit of the indications and clinical impact of prolonged ambulatory small intestinal manometry.

Small bowel manometry is a diagnostic test available only in a few specialized referral centers. Its exact place in the management of refractory symptoms is controversial. The records of all patients who underwent 24-hour ambulatory duodenojejunal manometry over a 6-year period were retrospectively reviewed. We studied the clinical indications for small bowel manometry, and reviewed the impact of manometric findings on the clinical outcome. One hundred and forty-six studies were performed in 137 patients (46M, 91F) with a mean age of 44.9±15.7years. Mean follow-up duration was 15.1±22.6months. Appropriate endoscopic, radiological and gastric scintigraphy studies were performed in all patients prior to small bowel manometry. Criteria for abnormal motor activity were based on Bharucha's classification. The indications for small bowel manometry were chronic abdominal pain (n=43), slow-transit constipation (n=17), refractory gastroparesis (n=16), chronic diarrhea (n=7), recurrent episodes of subocclusion (n=16), postsurgical evaluation (n=36), suspicion of gut involvement in systemic disease (n=9), and unexplained nausea (n=2). The most common finding was a normal 24-hour ambulatory small bowel manometry (n=113). Thirty-three studies yielded abnormal findings which included extrinsic neuropathy (n=6), intrinsic neuropathy (n=18), intestinal myopathy (n=2), and subocclusion (n=7). Ambulatory small bowel manometry excluded a generalized motility disorder in 77% and had a significant impact on the subsequent clinical course in 23%. Ambulatory small bowel manometry is a useful and safe diagnostic tool to complement traditional investigative modalities in patients with severe unexplained abdominal symptoms.

Ventromedial medulla inhibitory neuron inactivation induces REM sleep without atonia and REM sleep behavior disorder

Despite decades of research, there is a persistent debate regarding the localization of GABA/glycine neurons responsible for hyperpolarizing somatic motoneurons during paradoxical (or REM) sleep (PS), resulting in the loss of muscle tone during this sleep state. Combining complementary neuroanatomical approaches in rats, we first show that these inhibitory neurons are localized within the ventromedial medulla (vmM) rather than within the spinal cord. We then demonstrate their functional role in PS expression through local injections of adeno-associated virus carrying specific short-hairpin RNA in order to chronically impair inhibitory neurotransmission from vmM. After such selective genetic inactivation, rats display PS without atonia associated with abnormal and violent motor activity, concomitant with a small reduction of daily PS quantity. These symptoms closely mimic human REM sleep behavior disorder (RBD), a prodromal parasomnia of synucleinopathies. Our findings demonstrate the crucial role of GABA/glycine inhibitory vmM neurons in muscle atonia during PS and highlight a candidate brain region that can be susceptible to α-synuclein-dependent degeneration in RBD patients.

Bimolecular Fluorescence Complementation of Alpha-synuclein Demonstrates its Oligomerization with Dopaminergic Phenotype in Mice

Alpha-synuclein (αSyn) is encoded by the first causal gene identified in Parkinson's disease (PD) and is the main component of Lewy bodies, a pathological hallmark of PD. aSyn-based animal models have contributed to our understanding of PD pathophysiology and to the development of therapeutics. Overexpression of human wildtype αSyn by viral vectors in rodents recapitulates the loss of dopaminergic neurons from the substantia nigra, another defining pathological feature of the disease. The development of a rat model exhibiting bimolecular fluorescence complementation (BiFC) of αSyn by recombinant adeno-associated virus facilitates detection of the toxic αSyn oligomers species. We report here neurochemical, neuropathological and behavioral characterization of BiFC of αSyn in mice. Overexpression and oligomerization of αSyn through BiFC is detected by conjugated fluorescence. Reduced striatal dopamine and loss of nigral dopaminergic neurons are accompanied neuroinflammation and abnormal motor activities. Our mouse model may provide a valuable tool to study the role of αSyn in PD and to explore therapeutic approaches.

Emotional, affective and behavioral disorders in a behavioral variant of frontotemporal dementia

To determine the prevalence and severity of non-cognitive nervous and psychiatric disorders (NNPD) in a behavioral variant of frontotemporal dementia. Twenty-nine patients with BVFTD, aged from 41 to 73 years (mean 60.7±8.1 years), were studied. All patients underwent neurological and neuropsychological examinations. NNPD were assessed using the Neuropsychiatric Inventory (J. Cummings et al). Twenty-seven patients underwent brain MRI with T1, T2 and FLAIR sequences. The most clinically significant symptoms of NNPD were apathy, behavioral disinhibition, eating disorders, abnormal motor activity and euphoria. Irritability, sleep disorders and excitement were less frequent. Anxiety and depression were identified in 13.8 and 20.7% of the patients, respectively. The severity of NNPD can increase and their spectrum can be qualitatively changed with the disease progression that indicates the spread of the neurodegenerative process. Patients with BVFTD had all NNPD with the exception of delusion and hallucinations. The character and degree of severity of some emotional, affective and behavioral disorders are associated with the predominant localization of the pathological process in frontal and temporal brain regions.