Reactivation-induced motor skill learning

Learning motor skills commonly requires repeated execution to achieve gains in performance. Motivated by memory reactivation frameworks predominantly originating from fear-conditioning studies in rodents, which have extended to humans, we asked the following: Could motor skill learning be achieved by brief memory reactivations? To address this question, we had participants encode a motor sequence task in an initial test session, followed by brief task reactivations of only 30 s each, conducted on separate days. Learning was evaluated in a final retest session. The results showed that these brief reactivations induced significant motor skill learning gains. Nevertheless, the efficacy of reactivations was not consistent but determined by the number of consecutive correct sequences tapped during memory reactivations. Highly continuous reactivations resulted in higher learning gains, similar to those induced by full extensive practice, while lower continuity reactivations resulted in minimal learning gains. These results were replicated in a new independent sample of subjects, suggesting that the quality of memory reactivation, reflected by its continuity, regulates the magnitude of learning gains. In addition, the change in noninvasive brain stimulation measurements of corticospinal excitability evoked by transcranial magnetic stimulation over primary motor cortex between pre- and postlearning correlated with retest and transfer performance. These results demonstrate a unique form of rapid motor skill learning and may have far-reaching implications, for example, in accelerating motor rehabilitation following neurological injuries.

Motor skill learning, in healthy or clinical populations, usually requires extensive execution of a motor task to achieve gains in performance. These gains are accumulated in two different time windows: during skill execution (online learning, see refs. 1–3) and between sessions, possibly through offline consolidation processes (offline learning, see refs. 4–6). Interestingly, frameworks stemming from synaptic-level studies (7–9), and further supported by evidence in rodents (10–13) and humans (14–20), suggest that even fully consolidated memories, presumably stable, can be strengthened, updated, or degraded following their reactivation. Could such brief memory reactivations enhance motor skill performance without extensive practice over multiple sessions? Motivated by a proof-of-principle study in a different domain, visual perceptual learning (15), here, we tested whether brief reactivations of an encoded motor skill can induce learning gains. We additionally tested whether such form of rapid learning generalizes to the untrained hand. The possibility of achieving skill improvements with a minimal amount of task execution could strongly impact skill learning research and have promising potential for the development of strategies to improve practice efficiency in daily life and following neurological impairments.To test the ability of memory reactivations to induce motor skill learning, participants practiced a motor sequence task (21) in which they were asked to type a five-digit sequence as fast and as accurate as they could (see Materials and Methods). The motor skill was first encoded in an initial test session, with a retest session conducted following 1 wk. Participants in the “Reactivations” group performed brief reactivations on two separate days between the test and retest. Each of these reactivation sessions lasted only 30 s, in which participants reactivated the skill memory by briefly performing a single trial of the task (Fig. 1A). The “Control” group performed only test and retest sessions without memory reactivations. Participants in the “Full Practice” group performed two full training sessions (12 trials each) between the test and retest. Learning gains were quantified as the difference in performance between the last trial of the test session and the first retest trial (5, 22–24), with performance quantified as the number of correct sequences tapped, a highly common measure combining both speed and accuracy (17, 23, 25, 26).Open in a separate windowFig. 1.Reactivation-induced learning gains. (A) Experimental design. Subjects first encoded the motor skill memory in a test session including 12 trials of the task and performed a retest session following 1 wk, followed by an intermanual transfer test. Participants in the Reactivations group (composed of High Continuity and Low Continuity) performed brief reactivations between test and retest in which they reactivated their skill memory by performing only a single 30 s trial of the task. Participants in the Full Practice group performed full 12 trials training sessions between test and retest. The Control group performed only test and retest sessions without reactivations. (B) An illustrated explanation of the CS calculation. In both examples, the number of correct sequences, errors, and total key presses are identical, but the CS is different. (C) Single-trial performance for all groups (High Continuity Reactivations marked in light blue, Low Continuity Reactivations in light red, Control in gray, and Full Practice in purple. The combined Reactivations groups are illustrated in dashed black). (D) Test versus retest single-subject performance presented in a scatterplot along a unit slope line (y = x) where each point reflects a participant (5, 46). Data accumulating above the unit line reflect subjects who improved from test to retest, expressing learning gains, while data points below the line indicate degraded retest performance. (E) Dashed black bars (corresponding to the right y-axis) reflect the percentage of participants on each side of the unit slope line in D, and the colored bars reflect the mean performance in test and retest sessions (corresponding to the left y-axis). (F) Mean transfer test performance compared to test performance. *P < 0.05, **P < 0.001. Error bars represent SEM.Because of the variable efficacy of reactivations, we reasoned that the quality of reactivations may determine their efficacy in inducing learning gains. Unintentional errors during reactivation might reactivate a different version of the memory and could strengthen erroneous memories instead of the original memory trace. This could possibly cause a decrease in learning gains or even result in deteriorated performance of the original memory. This is consistent with the concept of interruptions, previously suggested to affect task performance (27, 28), possibly by preventing encoding of coherent representations of memories (27, 29, 30). Accordingly, we reasoned that continuity, reflecting minimal interruptions, might play a role in defining the efficacy of reactivations. To that effect, “High” and “Low Continuity Reactivations” were separately analyzed (see Materials and Methods and Results). In addition, a replication experiment was conducted to confirm the role of continuity in reactivation efficacy.     

Verylow frequency variability in arterial blood pressure and blood volume pulse

Several parameters of the cardiovascular system fluctuate spontaenously owing to the activity of the autonomic nervous system. In the study, the simultaneous very low frequency (VLF) fluctuations of the arterial blood pressure, the tissue blood content and the tissue blood volume pulse are investigated. The latter two parameters are derived from the baseline BL and the amplitude AM of the photoplethysmographic (PPG) signal, measured on the fingertips of 20 healthy male subjects: the changes in the PPG parameters AM and BV, defined by BV=const.-BL, are related to the change in the tissue blood volume pulse and the total tissue blood volume, respectively. The VLF fluctuations in BV and AM are directly correlated, those of AM preceding those of BV by 4–13 heart-beats. The VLF fluctuations in the systolic (SBP) and the diastolic (DBP) blood pressure are inversely correlated to those of AM and BV, those of AM preceding those of SBP and lagging behing those of DBP by about one heart-beat. For most subjects, the period P of the PPG pulse, which is equal to the cardiac cycle period, directly correlates with AM and BV and inversely correlates with DBP and SBP. On average, the fluctuations fluctuations in tissue blood volume, systolic blood volume pulse, diastolic and systolic blood pressure, and heart period, together with their interrelationship, can provide a better understanding of the autonomic nervous control of the peripheral circulation and a potential tool for the evaluation of its function.     

The pharyngo-laryngeal deficit in the acute form of infantile spinal muscular atrophy (Werdnig-Hoffmann disease)

The major complication in the acute form of infantile spinal muscular atrophy is the aspiration phenomenon, due to the pharyngo-laryngeal deficit. The radiographic findings of this deficit are characterized by epipharyngeal regurgitation, hypopharyngeal distention, good function of the cricopharyngeal sphincter and absence of epiglottic closure during the act of deglutition. The differential diagnosis of other neuromuscular entities is discussed in view of two documented radiographic cases.     

Cerebrospinal fluid zinc concentrations in febrile convulsions.

Zinc modulates the activity of glutamic acid decarboxylase, the rate limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter. Low cerebrospinal fluid GABA values have been reported in association with several seizure disorders, including febrile convulsions. It is also known that fever and/or infections may cause a reduction in serum zinc concentrations. In this study the hypothesis that febrile convulsions are related to low cerebrospinal fluid zinc was tested. Cerebrospinal fluid zinc concentrations were measured in 66 febrile children: 32 with febrile convulsions, 18 with fever but without convulsions, and 16 with aseptic (viral) meningitis. There was no statistically significant difference in the cerebrospinal fluid zinc between the three groups of children, and the mean concentration was 26.2 micrograms/l. No significant relationship was found between either age, gender, maximal temperature, type of infection, or time of performance of the lumbar puncture and cerebrospinal fluid zinc concentration. These results do not support the hypothesis that febrile convulsions are related to reduced cerebrospinal fluid zinc concentrations.     

Analysis of umbilical artery flow parameters during fetal variable decelerations using computerized Doppler waveforms

Umbilical artery velocity waves were obtained by Doppler ultrasonography before, during, and after 20 episodes of fetal heart rate (FHR) variable decelerations (VD) during the active stage of labor in 8 women. During 50% of the VD periods, the umbilical artery resistance flow parameters increased significantly (p < 0.01). The increase in resistance preceded the decrease in FHR in six episodes (30%) of VD (AR-VD group; arterial resistance VD) and did not precede the change in FHR in another ten episodes (50%) of VD (VR-VD group; venous resistance VD). In the AR-VD group the FHR accelerations occurred before the decelerations in only 1 case (17%), while in the VR-VD group FHR accelerations preceded the decelerations in 8 out of the 10 episodes (80%). Using these Doppler studies, it may be possible to differentiate between two groups of VD: AR-VD - which are caused by umbilical artery occlusion and thus preceded by a measurable increase in umbilical artery resistance - and VR-VD - which are not preceded by a measurable increase in umbilical artery resistance and may be caused by fetal hypoxia.     

Restoration modalities of severely injured anterior teeth--gingival integration, papillae support, and predictable imperfections

This article presents 4 cases, each describing a different dental trauma and a different treatment modality. Because of various limitations, none of the results presented is esthetically perfect, but the outcomes were acceptable to both the operators and the patients. Such limitations should be predicted and discussed with patients before beginning treatment and should be regarded as acceptable compromises, unless other less conservative treatments are to be used.     

Effect of a fluoride varnish on the margin leakage and retention of luted provisional crowns

STATEMENT OF PROBLEM: Provisional crowns cemented with provisional luting agents are susceptible to washout, margin leakage, and secondary caries when placed for a prolonged period. PURPOSE: This study was conducted to determine the effect of combining a varnish containing 2.26% NaF with 2 provisional luting agents on the margin leakage and retention of provisional crowns. MATERIAL AND METHODS: Acrylic resin provisional crowns were fabricated for 8 shoulder-prepared molars. The eight provisional (N=24) crowns were luted individually with Temp-Bond (TB), Freegenol (FG), or Duraphat (DU). Specimens were thermocycled 500 times (5 degrees and 60 degrees C) with a 1-minute dwell time, stored in 100% relative humidity at 37 degrees C for 6 days, and then immersed in a 0.5% Gentian violet solution for 24 hours. Seven days after cementation, a removal test of the crowns (shear retention test) was conducted with a universal testing machine at a crosshead speed of 5 mm/min. Retention was determined as the maximum recorded force needed for crown dislodgment. DU varnish was applied to the inner surface of the dislodged crowns with no removal of the cement layer TB, FG (N=16). The crowns were relined with a 0.5-mm layer of acrylic resin and luted with a combination of luting agent and DU (TB, FG) N=16. No luting agent (NC) served as the control (N=8). Results were analyzed with the Wilcoxon matched-pairs signed-ranks test. Leakage at the margins was assessed with a 4-level dye penetration scale, and statistical differences were identified with a chi(2) test. All hypothesis testing was conducted at the 95% level of confidence. RESULTS: The mean 7-day retention forces were as follows: 44.5 N (Temp-Bond), 51.6 N (Freegenol), and 35.9 N (Duraphat). There were no significant differences among these values. Duraphat combined with Freegenol decreased the retention of provisional crowns, but Duraphat combined with Temp-Bond increased the retention of provisional crowns by 69-145%. Duraphat alone and in combination with both provisional luting agents significantly reduced margin leakage (P<.05). The least margin leakage was evident when the provisional crowns were luted with Duraphat alone. CONCLUSION: With regard to retention and margin leakage, the results of this study suggest that Duraphat varnish can be successfully used as provisional luting agent for single provisional crowns.     

The ethics of the placebo in clinical practice

While discussions of the ethics of the placebo have usually dealt with their use in a research context, the authors address here the question of the placebo in clinical practice. It is argued, firstly, that the placebo can be an effective treatment. Secondly, it is demonstrated that its use does not always entail deception. Finally guidelines are presented according to which the placebo may be used for clinical purposes. It is suggested that in select cases, use of the placebo may even be morally imperative. The argument is illustrated by three case vignettes.     

Convulsions in childhood shigellosis. Clinical and laboratory features in 153 children

We studied 153 children who experienced convulsions associated with shigellosis. The male-female ratio was 1.2:1.0. Thirty-six children had a previous history of febrile convulsions, and 31 children had a family history of convulsive disorder. Most of the children were 0.5 to 3 years of age, although 49 (32%) were older than 3 years of age and 20 (13.1%) were older than 5 years of age. All children were febrile; in 75% of the children, the temperature was over 39 degrees C. The majority of the children had generalized, self-limited convulsions, which lasted less than ten minutes. In 30 children the seizures were categorized as complex; ten of them had recurrent episodes, although none had any residual neurologic deficit. The total leukocyte count was usually within normal limits, but the differential count characteristically showed a marked increase in the number of band forms. Hypocalcemia (blood calcium level, less than 9.01 mg/dL [less than 2.25 mmol/L]) was observed in four patients; hyponatremia (blood sodium level, 130 mEq/L [130 mmol/L]), in 11 patients; and hypernatremia (blood sodium level, 157 mEq/L [157 mmol/L]), in one patient. Electroencephalographic (EEG) studies were performed in ten children, and lumbar punctures were performed in 34 children; both procedures usually yielded normal results. Shigella sonnei was isolated from 69% of the children; Shigella flexneri from 25%; Shigella boydii from 5%; and Shigella dysenteriae from 1%. Due to the benign and self-limited nature of most of the convulsions, neither diagnostic procedures, nor drug therapy, are usually necessary. These measures should, however, be considered in complicated cases characterized by focal or prolonged seizures.     

Placental transfer of analogs of glucose and amino acids in experimental intrauterine growth retardation.

We have employed the model in which one uterine artery is ligated to study maternofetal transport and tissue uptake of glucose and amino acids in the intrauterine growth-retarded rat. On the 18th day of gestation, the artery supplying one uterine horn was ligated. Two days later the rats received [3H]2-deoxyglucose and [14C]alpha-aminoisobutyric acid iv. One hour later the growth-retarded and control fetuses were delivered by Cesarean section and appropriate blood samples were obtained. The growth-retarded fetuses had an average weight reduction of 27%, significantly increased placental to fetal weight ratio and brain to body ratio, and a significantly reduced liver to body body ratio. Total radioactivity derived from tritiated deoxyglucose in whole fetal tissues, placenta, liver, and brain were significantly decreased in the intrauterine growth-retarded (IUGR) fetuses; this was also true per gram of tissue except for liver. Liver to plasma, brain to plasma, and whole fetal tissue to plasma 3H ratios were significantly increased in the IUGR group. The radioactivity derived from [14C]alpha-aminoisobutyric acid was significantly reduced in whole fetal tissues, placenta, liver, and brain in the IUGR fetuses whether expressed per whole organ or per gram of tissue. Significant differences in liver to plasma, brain to plasma, and whole tissue to plasma 14C ratios were not observed.