A Comparison of Mother's Milk and the Neonatal Urine Metabolome: A Unique Fingerprinting for Different Nutritional Phenotypes.

The ability of metabolomics to provide a snapshot of an individual's metabolic state makes it a very useful technique in neonatology for investigating the complex relationship between nutrition and the state of health of the newborn. Through an 1H-NMR metabolomics analysis, we aimed to investigate the metabolic profile of newborns by analyzing both urine and milk samples in relation to the birth weight of neonates classified as AGA (adequate for the gestational age, n = 51), IUGR (intrauterine growth restriction, n = 14), and LGA (large for gestational age, n = 15). Samples were collected at 7 ± 2 days after delivery. Of these infants, 42 were exclusively breastfed, while 38 received mixed feeding with a variable amount of commercial infant formula (less than 40%) in addition to breast milk. We observed a urinary spectral pattern for oligosaccharides very close to that of the corresponding mother's milk in the case of exclusively breastfed infants, thus mirroring the maternal phenotype. The absence of this good match between the infant urine and human milk spectra in the case of mixed-fed infants could be reasonably ascribed to the use of a variable amount of commercial infant formulas (under 40%) added to breast milk. Furthermore, our findings did not evidence any significant differences in the spectral profiles in terms of the neonatal customize centile, i.e., AGA (adequate for gestational age), LGA (large for gestational age), or IGUR (intrauterine growth restriction). It is reasonable to assume that maternal human milk oligosaccharide (HMO) production is not or is only minimally influenced by the fetal growth conditions for unknown reasons. This hypothesis may be supported by our metabolomics-based results, confirming once again the importance of this approach in the neonatal field.

Use of intravenous sodium bicarbonate in neonatal intensive care units in Italy: a nationwide survey.

BACKGROUND: Metabolic Acidosis (MA) is a disturbance of the acid-base balance that can occur in preterm and critically ill term neonates due to different etiologies. Intravenous sodium bicarbonate (SB) has been traditionally used to correct such unbalance, despite the lack of evidence about its safety and efficacy. In literature, reported undesirable effects of treatment with SB in neonates include worsening of intracellular acidosis, impairment of myocardial function, cerebral blood flow fluctuations and intracranial hemorrhage. A national survey was conducted by the Neonatal Pharmacotherapy Study Group of the Italian Society of Neonatology with the aim to assess and describe attitudes and practices concerning the use of SB, particularly for the treatment of MA in Italian NICUs. METHODS: A questionnaire regarding treatment of MA and SB prescription habits was sent to the directors of 120 Italian NICUs from June 2017 to March 2018. RESULTS: The survey response rate was 97.5% (117/120 centers). Findings showed that in 55% of the surveyed NICUs (64/117 units) it is common practice to correct MA with intravenous SB. On the other hand, the remaining 45% of the units try to solve the metabolic disturbances adopting different approaches (improving perfusion, adjusting ventilation parameters or increasing blood volume). Moreover, to prevent the occurrence of MA, 37.6% of the NICUs (44/117) include buffer salts (lactate, acetate or both) in parenteral nutrition prescriptions. SB is also used as a treatment for other conditions, mainly pathologies with bicarbonate loss and tubular acidosis (respectively in 53.8 and 32.5% of the NICUs). CONCLUSION: This survey showed how SB is a commonly used treatment for MA in more than half of Italian NICUs, with indications and prescription criteria that significantly vary across centers. Based on current knowledge, it is reasonable to suggest that the management of neonatal MA should be firstly directed to identify the underlying disorders. Thus, the use of SB should be reserved only for selected cases, also considering the severity of SB adverse effects and the lack of evidence about its efficacy. Guidance for the management of MA is required to harmonize practices and reduce the use of potentially inappropriate and unsafe treatments.

Nationwide survey of neonatal transportation practices in Italy.

BACKGROUND: Despite regionalization of perinatal care provides for the "in utero" transfer of high-risk pregnancies, there will always be a number of neonates who undergo acute inter-facility transport. The presence of a well-organized Neonatal Emergency Transport Service (NETS) can prevent and reduce risks of transportation, especially for very preterm infants, and is therefore mandatory for any program of regionalization of perinatal care. Italian National Health System is highly decentralized and Regions are autonomous to structure, plan and delivery their regional health services. Consequently, organization models and resources available vary widely and significant regional differences in access and quality of health services have been reported in the past years. A national survey was conducted in 2015 by the neonatal transport study group of the Italian Society of Neonatology with the aim to describe neonatal transfer practices and to assess the Neonatal Emergency Transport Services (NETS) status in the 20 Italian regions. METHODS: A questionnaire regarding neonatal transfer practices and NETS activity for the previous year (2014) was sent to the 44 NETS operating in the 20 Italian regions. Demographic data were obtained from the Italian National Statistical Institute (ISTAT). RESULTS: The overall survey response rate was 100%. In 2014, only 12 (60%) of the 20 Italian regions were fully covered by NETS, 3 (15%) regions were partially covered, while neonatal transport was not available in 5 (25%) regions. Overall, in 2014, the 44 NETS operating in Italy transported a total of 6387 infants, including 522 (8.17%) having a gestational age < 28 weeks. CONCLUSIONS: The organization of NETS in Italy is devolved on a regional basis, resulting in a large heterogeneity of access and quality to services across the country. Where available, NETS are generally well-equipped and organized but limited volume of activities often cannot guarantee adequate levels of skills of personnel or an appropriate cost-efficiency ratio. The regions reported with lack of NETS have managed, or are trying, to fill the gap, but continuing efforts to reduce regional differences in the availability and quality of services are still needed.

Trace elements, oxidative status and antioxidant capacity as biomarkers in very low birth weight infants.

Reference data on trace elements, oxidative status and antioxidants in very low birth weight infants (VLBW) are limited and need to be updated for use in clinical settings. Serum and urine of 30 VLBW infants (mean weight, 1167g) at mean age of 23.8 (t0) and 37.8 (t1) days were analyzed. Cadmium (Cd), copper (Cu), iron (Fe), mercury (Hg), manganese (Mn), selenium (Se) and zinc (Zn), nitrate/nitrite (NOx), catalase (CAT), CuZnFeMn-superoxide dismutases (CuZnFeMn-SODs), total antioxidant capacity (SAC: sum of thiols, proteins, bilirubin, uric acid, ß-beta-carotene, ascorbic acid, vitamin E) and total oxidative status (SOS: sum of lipo- and hydroperoxides) were determined. A higher urinary excretion of Cu and Zn was observed at t0 than at t1; while an increase in urine Cd was found at t1 respect to t0. A deficiency in serum levels of Cu and Zn was also found. A lower CAT activity, a higher total oxidants level (SOS) and a reduction of total antioxidant barriers (SAC) were observed in some infants. No Fe and Mn deficiency or Hg overload was found; also CuZnFeMn-SODs and NOx levels did not change. The findings showed that losses of trace elements and incomplete mineral body stores were more pronounced in the earlier life stage (at 23.8th day) than later on; moreover, antioxidant defenses were poor and lipo- and hydroperoxides were higher still at 5 weeks of infants' life.

Prevalence and determinants of preconception folic acid use: an Italian multicenter survey.

BACKGROUND: Women in many countries are advised to use folic acid supplements before and early during pregnancy to reduce the risk of neural tube defects in their infants. This study aimed to update the prevalence and to identify possible determinants of preconception folic acid supplement use in Italian women. METHODS: The study was based on cross-sectional data from seven maternity clinics located in six Italian regions from January to June, 2012. Data on maternal characteristics and supplement use were collected for 2,189 women using a self-administered questionnaire. RESULTS: Preconception folic acid use was reported by 23.5 % (n = 515) of the participants. Of these, 479 (93 %) women had taken folic acid supplements on a daily basis as recommended by the health authorities. Women who both had intended their pregnancy and had requested a preconception health visit to a doctor/gynecologist were substantially more likely than the reference group to initiate folic acid supplementation before their pregnancy (48.6 versus 4.8 %). Preconception folic acid use was also associated with higher maternal age, higher education, marriage/cohabitation, lower parity, infertility treatments, and chronic disease. CONCLUSIONS: Data from seven maternity clinics located in six Italian regions indicate that preconception folic acid supplement use in many Italian women is low. Women who do not plan their pregnancy or do not request a preconception health visit to their doctor have among the lowest prevalence of preconception folic acid use. Improving folate status in these and other supplemental non-users may have important disease preventive effects.

Exploring the Role of Different Neonatal Nutrition Regimens during the First Week of Life by Urinary GC-MS Metabolomics.

In this study, a gas-chromatography mass spectrometry (GC-MS) metabolomics study was applied to examine urine metabolite profiles of different classes of neonates under different nutrition regimens. The study population included 35 neonates, exclusively either breastfed or formula milk fed, in a seven-day timeframe. Urine samples were collected from intrauterine growth restriction (IUGR), large for gestational age (LGA), and appropriate gestational age (AGA) neonates. At birth, IUGR and LGA neonates showed similarities in their urine metabolite profiles that differed from AGA. When neonates started milk feeding, their metabolite excretion profile was strongly characterized by the different diet regimens. After three days of formula milk nutrition, urine had higher levels of glucose, galactose, glycine and myo-inositol, while up-regulated aconitic acid, aminomalonic acid and adipic acid were found in breast milk fed neonates. At seven days, neonates fed with formula milk shared higher levels of pseudouridine with IUGR and LGA at birth. Breastfed neonates shared up-regulated pyroglutamic acid, citric acid, and homoserine, with AGA at birth. The role of most important metabolites is herein discussed.

Off-label and unlicensed drug treatments in Neonatal Intensive Care Units: an Italian multicentre study.

PURPOSE: The use of medicines among newborns admitted to intensive care units is characterized by a high prevalence of off-label/unlicensed use and a wide variability in the absence of international guidelines. A prospective cross-sectional study was organized with the aim to analyse drug prescriptions among all 107 Italian level III neonatal intensive care units. METHODS: An online questionnaire was used to collect detailed information for each newborn, and a classification was made about the license status of all prescriptions. In addition, prescriptions were analysed taking into account a practical guide prepared by the Italian Society of Neonatology (ISN). RESULTS: The 1-day survey (May­July 2014) regarded 220 newborn infants admitted to 36/107 Italian neonatal intensive care units: 191 prematures and 29 born at term. In total, 720 prescriptions (corresponding to 79 different drugs) were analysed: 191 (26.5 %) followed the terms of the product license, 529 (73.5 %) were off-label or unlicensed: 193/220 newborns (87.7 %) received at least one off-label/unlicensed prescription. Antiinfectives were the most common medicine used, followed by respiratory drugs and antianaemics; in an off-label manner, the most common was cardiovascular and central nervous system (CNS) drugs, gastrointestinals and antiinfectives. The most common categories of off-label use were age (34.4 %) and dosing frequency (20.6 %). Compared to ISN practical guide, prescriptions adhered more frequently to indications (100 % for ampicillin/sulbactam, >80 % for ampicillin, fluconazole, fentanyl, ranitidine and vancomicin). CONCLUSIONS: Our results confirm the high prevalence of off-label/unlicensed drug use in the neonatal population and underline a better adherence to indications based on clinical practice, suggesting the need to update information contained in the data sheets of medicines.

(1)H NMR-based urine metabolic profile of IUGR, LGA, and AGA newborns in the first week of life.

Under conditions of non-optimal supply of nutrients, maternal diet during gestation can alter the balance between anabolic and catabolic pathways of fetus and triggers an effect of programming to the metabolic syndrome. Metabolomics is an analytical technique that has been recently attracting increasing interest for the identification of biomarkers of dietary exposure. In this study, a NMR-based metabolomic approach was employed for an explorative analysis of the time-related urinary metabolic profiles of three groups of newborns receiving a different fetal nutrition: adequate for gestational age (AGA), with intrauterine growth retardation (IUGR), and large for gestational age (LGA). Urine samples were collected over the first week of life. Application of Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) evidenced similar time-related modifications in the metabolic profiles of the three classes of infants, consisting mainly of changes in levels of taurine, creatinine, betaine, and glycine. Furthermore, alterations in the content of citrate and myo-inositol were found to be characteristic of IUGR and LGA, whole levels were higher with respect to controls, while higher contents of betaine and succinate were noted in AGA. Our results positively support the application of the metabolomic approach in the study of the metabolic pathways associated to fetal malnutrition.

Approaches to supporting lactation and breastfeeding for very preterm infants in the NICU: a qualitative study in three European regions.

OBJECTIVES: To explore differences in approaches to supporting lactation and breastfeeding for very preterm infants in neonatal intensive care units (NICU) in 3 European regions. DESIGN: Qualitative cross-sectional study carried out by means of face-to-face semistructured interviews. Verbatim transcripts were coded using a theoretical framework derived from the literature and supplemented by data-driven concepts and codes. SETTING: 4 purposively selected NICUs in each of 3 European regions in 2010 (Ile-de-France in France, Lazio in Italy, and the former Trent region in the UK). PARTICIPANTS: NICU staff members (n=22). RESULTS: Policies and practices for managing mother's own milk for very preterm babies differed between regions, and were much more complex in Ile-de-France than in the Trent or Lazio regions. Staff approaches to mothers to initiate lactation differed by region, with an emphasis on the nutritional and immunological value of human milk in the Trent region and on the 'normalising' effect of breastfeeding on the mother-child relationship in Lazio. French and English staff expressed conflicting opinions about the use of bottles, which was routine in Italy. Italian informants stressed the importance of early maternal milk expression and feeding, but also mentioned discharging infants home before feeding at the breast was established. In Ile-de-France and Trent, successful feeding from the breast was achieved before discharge, although this was seen as a factor that could prolong hospitalisation and discourage continued breastfeeding for some women. CONCLUSIONS: Targeted health promotion policies in the NICU are necessary to increase the number of infants receiving their mother's milk and to support mothers with transfer of the infant to the breast. Integrating knowledge about the different approaches to lactation and breastfeeding in European NICUs could improve the relevance of recommendations in multiple cultural settings.

Is synchronised NIPPV more effective than NIPPV and NCPAP in treating apnoea of prematurity (AOP)? A randomised cross-over trial.

BACKGROUND: Apnoea, desaturations and bradycardias are common problems in preterm infants which can be treated with nasal continuous positive airway pressure (NCPAP) and nasal intermittent positive pressure ventilation (NIPPV). It is unclear whether synchronised NIPPV (SNIPPV) would be even more effective. OBJECTIVE: To assess the effects of flow-SNIPPV, NIPPV and NCPAP on the rate of desaturations and bradycardias in preterm infants and, secondarily, to evaluate their influence on pattern of breathing and gas exchange. PATIENTS AND METHODS: Nineteen infants (mean gestational age at study 30 weeks, 9 boys) with apnoeic spells were enrolled in a randomised controlled trial with a cross-over design. They received flow-SNIPPV, NIPPV and NCPAP for 4 h each. All modes were provided by a nasal conventional ventilator able to provide synchronisation by a pneumotachograph. The primary outcome was the event rate of desaturations (≤80% arterial oxygen saturation) and bradycardias (≤80 bpm) per hour, obtained from cardiorespiratory recordings. The incidence of central apnoeas (≥10 s) as well as baseline heart rate, FiO2, SpO2, transcutaneous blood gases and respiratory rate were also evaluated. RESULTS: The median event rate per hour during flow-SNIPPV, NIPPV and NCPAP was 2.9, 6.1 and 5.9, respectively (p<0.001 and 0.009, compared with flow-SNIPPV). Central apnoeas per hour were 2.4, 6.3 and 5.4, respectively (p=0.001, for both compared with flow-SNIPPV), while no differences in any other parameter studied were recorded. CONCLUSIONS: Flow-SNIPPV seems more effective than NIPPV and NCPAP in reducing the incidence of desaturations, bradycardias and central apnoea episodes in preterm infants.

Investigation of the ¹H-NMR based urine metabolomic profiles of IUGR, LGA and AGA newborns on the first day of life.

(1)H-NMR spectroscopy coupled with multivariate statistical analysis was used for the first time to compare the urinary NMR metabolic profiles of neonates with intrauterine growth retardation (IUGR) and large for gestational age (LGA). For the sake of comparison, infants who were adequate for gestational age (AGA) were also analyzed. Pattern recognition methods, including Principal Component Analyses (PCA), Partial Least Squares Discriminant Analysis (PLS-DA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA), were used to analyze NMR data. Clear differences among the metabolic profiles of AGA, IUGR and LGA were observed. The main metabolites responsible for these differentiations were identified as myo-inositol, creatinine, creatine, citrate, urea and glycine. In particular, among these, myo-inositol may be a potential biomarker of an altered glucose metabolism during fetal development both in IUGR and LGA. This study highlights the applicability of NMR-based metabolomics for improving the understanding of the relations among nutrition, integrated metabolism and health in neonatology.

Bradykinesia of posed smiling and voluntary movement of the lower face in Parkinson's disease.

OBJECTIVE: Impaired facial expression, including spontaneous and emotional movements such as smiling, has been often reported in Parkinson's disease (PD). There is a general consensus that spontaneous smiling is abnormal in PD. Investigations on posed smiling yield contrasting results. Moreover, no study has yet addressed the relationship between posed smiling and abnormalities of voluntary movements of the lower face, global motor impairment and the effects of dopaminergic medication. METHODS: We investigated the kinematics of posed smiling (mimicking a smile shown in a picture) and those of voluntary movements of the lower face (showing the teeth as fast as possible - voluntary grinning) in 15 patients with PD (ON and OFF therapy) and in 16 healthy controls. Facial movements were recorded using a 3D optoelectronic system and analyzed using dedicated software. RESULTS: Some kinematic parameters of both posed smiling and voluntary grinning were abnormally lower in PD patients in comparison to healthy subjects. The kinematics of posed smiling correlated with those of voluntary grinning in PD patients but not in healthy controls. Posed smiling and voluntary grinning abnormalities were related to global motor severity but did not significantly improve upon L-dopa administration. CONCLUSIONS: These results suggest that posed smiling and voluntary grinning are both abnormal in PD patients and that they are likely mediated by a common pathophysiological mechanism.

Abnormal experimentally- and behaviorally-induced LTP-like plasticity in focal hand dystonia.

Idiopathic focal hand dystonia (FHD) arises from abnormal plasticity in the primary motor cortex (M1) possibly reflecting abnormal sensori-motor integration processes. In this transcranial magnetic stimulation (TMS) study in FHD, we evaluated changes in motor evoked potentials (MEPs) after intermittent theta burst stimulation (iTBS) and paired associative stimulation (PAS), techniques that elicit different forms of experimentally-induced long-term potentiation (LTP)-like plasticity in M1. We also examined behaviorally-induced LTP-like plasticity as reflected by early motor learning of a simple motor task. We studied 14 patients with FHD and 14 healthy subjects. MEPs were recorded before and after iTBS and PAS at the 25 ms interstimulus interval (PAS(25)) in separate sessions. Subjects did a simple motor task entailing repetitive index finger abductions. To measure early motor learning we tested practice-related improvement in peak velocity and peak acceleration. In FHD patients iTBS failed to elicit the expected MEP changes and PAS(25) induced abnormally increased MEPs in target and non-target muscles. In the experiment testing early motor learning, patients lacked the expected practice-related changes in kinematic variables. In FHD, the degree of early motor learning correlated with patients' clinical features. We conclude that experimentally-induced (iTBS and PAS) and behaviorally-induced LTP-like plasticity are both altered in FHD.

Weaning from mechanical ventilation.

Mechanical ventilation is often required by very preterm infants with respiratory failure, even if invasive respiratory support is related to lung injury and adverse neurologic outcomes. The exposure to mechanical ventilation should be therefore limited. Optimal extubation however remains challenging, as approximately 30% of intubated preterm infants fails attempted extubation due to poor respiratory drive, atelectasis, residual pulmonary function abnormalities or intercurrent illness. This review outlines the advantages of different weaning strategies that should be considered by neonatologists for current use to reduce unsuccessful extubation.

Blood cell counting in neonates: a comparison between a low volume micromethod and the standard laboratory method.

BACKGROUND: Iatrogenic anaemia caused by repeated blood sampling to monitor laboratory parameters can contribute, particularly in neonates, to the need for transfusion. "Point of care" laboratory equipment uses smaller amounts of blood for analytic determinations and could, therefore, help to prevent secondary anaemia. In this study we compared the results of haematological parameters measured using a standard laboratory method and using a "point of care" micromethod, with the aim of validating the use of this latter method in clinical practice in neonatology. MATERIALS AND METHODS: One hundred and fifty venous or capillary blood samples were taken from full-term or premature neonates 2-4 hours or 48 hours after birth. Each sample was processed by a standard haematology analyser and another micromethod instrument. Bland-Altman plots were constructed for each parameter and intra-class coefficients of correlation were calculated in order to evaluate the concordance between the two analysers. RESULTS: The concordance between the data obtained with the two analysers, expressed as the intra-class correlation, was 0.98 for white blood cell count, 0.97 for haemoglobin concentration, 0.96 for haematocrit, 0.95 for mean red cell volume and 0.98 for platelet count. The micromethod produced overestimated mean values for the leucocyte count (+1.27; p<0.001), haematocrit (+1.80; p<0.001) and platelet count (+13.55; p<0.001). CONCLUSIONS: Overall, the concordance between the values obtained with the two analysers was high for each of the parameters taken into consideration. In the case of haemoglobin and leucocytes, give the high intra-class correlation and lack of systematic overestimation of one method over another, the micromethod guarantees a correct evaluation; however, despite the high intra-class correlations for platelet counts, the systemic error seems to suggest that the micromethod cannot guarantee an appropriate evaluation of this parameter.

Bilateral clubfoot in three homozygous preterm triplets.

The etiology of congenital idiopathic talipes equinovarus deformity is unclear. Studies on populations, families, and twins have suggested a genetic component. However, the mode of inheritance does not fit classic patterns. The intrauterine posture and environmental and developmental causative factors have also been associated with the deformity. Neurologic, muscular, bony, connective tissue, and vascular structures can be affected. We present the case of monochorionic triplets with bilateral congenital idiopathic talipes equinovarus deformities. To the best of our knowledge, such a presentation has not been previously described and supports a genetic etiology of congenital idiopathic talipes equinovarus deformity.

Rates of bronchopulmonary dysplasia in very preterm neonates in Europe: results from the MOSAIC cohort.

BACKGROUND: A considerable local variability in the rate of bronchopulmonary dysplasia (BPD) has been recorded previously. OBJECTIVES: The objectives of the present study were to describe regional differences in the rate of BPD in very preterm neonates from a European population-based cohort and to further delineate risk factors. METHODS: 4,185 survivors to 36 weeks' postmenstrual age of 4,984 live-born infants born at 24+0-31+6 weeks' gestation in 2003 (the MOSAIC cohort) in 10 European regions were enrolled using predefined structured questionnaires. RESULTS: Overall median gestational age of preterms without BPD was 30 weeks (range 23-31), median birth weight 1,320 g (range 490-3,150) compared with 27 weeks (23-31) and 900 g (370-2,460) in those with BPD. The region-specific crude rate of BPD ranged from 10.2% (Italian region) to 24.8% (UK Northern region). Maternal hypertension, immaturity, male gender, small for gestational age, Apgar <7 and region of care were associated with an increased incidence of BPD on multivariate analysis. CONCLUSION: A wide variability of BPD between European regions may be explained by different local practices; the strongest association however was with degree of immaturity.

Variations in breastfeeding rates for very preterm infants between regions and neonatal units in Europe: results from the MOSAIC cohort.

OBJECTIVES: To compare breastfeeding rates at discharge for very preterm infants between European regions and neonatal units, and to identify characteristics associated with breast feeding using multilevel models. METHODS: Population-based cohort of 3006 very preterm births (22-31 weeks of gestation) discharged home from neonatal units in eight European regions in 2003. RESULTS: Breastfeeding rates varied from 19% in Burgundy to 70% in Lazio, and were correlated with national rates in the entire newborn population. Women were more likely to breast feed if they were older, primiparous and European; more premature, smaller and multiple babies or those with bronchopulmonary dysplasia were breast fed less. Variations across regions and neonatal units remained statistically significant after adjusting for maternal, infant and unit characteristics. CONCLUSION: It is possible to achieve high breastfeeding rates for very preterm infants, but rates varied widely across regions and neonatal units throughout Europe.

Metaplasticity of the human trigeminal blink reflex.

Although synaptic plasticity in the human cerebral cortex is governed by metaplasticity, whether a similar mechanism operates at brainstem level is unknown. In this study in healthy humans we examined the effects and interactions induced by pairing supraorbital nerve high-frequency electrical stimulation (HFS) protocols on the R2 component of the trigeminal blink reflex [Mao, J.B. & Evinger, C (2001) J Neurosci., 21:RC151(1-4)]. Changes in the R2 component were tested by pairing three different priming stimulation protocols inducing long-term potentiation (LTP)-like or long-term depression (LTD)-like effects (LTP-HFS and LTD-HFS), or no change (CONTROL-HFS) with a subsequent test LTP-HFS. Additionally, to examine changes in the R2 component induced by nonspecific factors, two CONTROL-HFS sessions were paired. Priming LTP-, LTD- or CONTROL-HFS potentiated, inhibited or left unchanged the area of the R2 component. Regardless of the type of priming LTP-, LTD- or CONTROL-HFS, the test LTP-HFS induced negligible differences in the R2 component. When two CONTROL-HFS sessions were paired, the test CONTROL-HFS increased the latency and markedly reduced the duration and area of the R2 component. The analysis of the normalized data across the first three experimental sessions, corrected for the inhibitory effects found in the fourth experiment, showed that the test LTP-HFS potentiated the R2 component area of the trigeminal blink reflex only when preceded by a priming LTD-HFS. We propose that homosynaptic metaplasticity might operate in the brainstem circuitry of the blink reflex.

Theta-burst stimulation over primary motor cortex degrades early motor learning.

Theta-burst stimulation (TBS) is currently used for inducing long-lasting changes in primary motor cortex (M1) excitability. More information is needed on how M1 is involved in early motor learning (practice-related improvement in motor performance, motor retention and motor consolidation). We investigated whether inhibitory continuous TBS (cTBS) is an effective experimental approach for modulating early motor learning of a simple finger movement in healthy humans. In a short task, 11 subjects practised 160 movements, and in a longer task also testing motor consolidation ten subjects practised 600 movements. During both experiments subjects randomly received real or sham cTBS over the left M1. Motor evoked potentials were tested at baseline and 7 min after cTBS. In the 160-movement experiment to test motor retention, 20 movements were repeated 30 min after motor practice ended. In the 600-movement experiment motor retention was assessed 15 and 30 min after motor practice ended, motor consolidation was tested by performing 20 movements 24 h after motor practice ended. Kinematic variables - movement amplitude, peak velocity and peak acceleration - were measured. cTBS significantly reduced the practice-related improvement in motor performance of finger movements in the experiment involving 160 movements and in the first part of the experiment involving 600 movements. After cTBS, peak velocity and peak acceleration of the 20 movements testing motor retention decreased whereas those testing motor consolidation remained unchanged. cTBS over M1 degrades practice-related improvement in motor performance and motor retention, but not motor consolidation of a voluntary finger movement.