Effects of DDAVP on movement planning and execution processes in the healthy elderly.

Effects of DDAVP on speed and consistency of planning and executing simple and complex movements in healthy older adults were studied. A simple reaction time (SRT) task, a single-plane movement task, and two tasks involving multiplane movements of distal upper extremities were performed with and/or without a 0.6 ml intranasal dose (60 micrograms) of DDAVP or placebo. Results indicated that DDAVP had no significant effect on speed or consistency of SRT processes, or the speed with which simple or complex movements were planned or executed. There was also no effect on retention of motor responses.     

Vasopressin analog (DDAVP) facilitates concept learning in human males

The effects of desmopressin acetate (DDAVP) were studied in normal males. Subjects were given 60μg of DDAVP, a placebo, or no treatment and were given several behavioral tests. DDAVP enhanced learning of all problems on a concept shift task but had no effect on visual memory, anxiety, blood pressure or heart rate. It was suggested that DDAVP may influence memory via its actions on attention.     

Vasopressin analog influences the performance of males on a reaction time task

The effects of desmopressin acetate (DDAVP), a vasopressin analogue, were investigated using the Sternberg Item Recognition Task. This task requires a subject to memorize a target set of up to four digits and then quickly to decide whether or not a given probe was in the original memory set. Fifteen college aged males were used as subjects in this study. Subjects received, in a double blind procedure, 0.6 ml of DDAVP (60 micrograms) or an equal volume of vehicle solution during the first test session. One week later, during the second test session, the hormone-placebo treatments were reversed. The results indicated significant main effects for set size and decision type and an interaction between treatment and session. Treatment with DDAVP during the second but not the first session improved performance at each set size as compared to treatment with the vehicle. These results indicate that DDAVP, combined with experience on this task, improved attentional processes but did not influence memory, which would have been indicated by an interaction between treatment and size of memory set.     

Dose-dependent effects of DDAVP on memory in healthy young adult males: a preliminary study

Although several studies have demonstrated the efficacy of the vasopressin analog DDAVP in enhancing human memory, no previous study has reported the dose-response relationship of DDAVP to memory in healthy young adults. The present study was undertaken to explore the dose-response curve for DDAVP on recall of implicational sentences. Five doses of DDAVP (0, 5, 15, 30, and 60 micrograms) were administered intranasally to healthy young adult male volunteers. Results demonstrated a facilitation in cued recall after treatment with the 60-micrograms dose and a general impairment in recall after treatment with the 15-micrograms dose. These effects were independent of subject's weight, vocabulary ability, and concentration of salivary cortisol.     

Neural correlates of the difference between working memory speed and simple sensorimotor speed: an fMRI study

The difference between the speed of simple cognitive processes and the speed of complex cognitive processes has various psychological correlates. However, the neural correlates of this difference have not yet been investigated. In this study, we focused on working memory (WM) for typical complex cognitive processes. Functional magnetic resonance imaging data were acquired during the performance of an N-back task, which is a measure of WM for typical complex cognitive processes. In our N-back task, task speed and memory load were varied to identify the neural correlates responsible for the difference between the speed of simple cognitive processes (estimated from the 0-back task) and the speed of WM. Our findings showed that this difference was characterized by the increased activation in the right dorsolateral prefrontal cortex (DLPFC) and the increased functional interaction between the right DLPFC and right superior parietal lobe. Furthermore, the local gray matter volume of the right DLPFC was correlated with participants' accuracy during fast WM tasks, which in turn correlated with a psychometric measure of participants' intelligence. Our findings indicate that the right DLPFC and its related network are responsible for the execution of the fast cognitive processes involved in WM. Identified neural bases may underlie the psychometric differences between the speed with which subjects perform simple cognitive tasks and the speed with which subjects perform more complex cognitive tasks, and explain the previous traditional psychological findings.     

Vasopressin analog (DDAVP) improves memory in human males

One specific analog of arginine vasopression, 1-desamine-8-D-arginine vasopressin (DDAVP), has been shown to improve learning and memory in humans. Healthy young male adult subjects treated with DDAVP demonstrated better memory for implicational sentences than did control subjects. The same treatment had no influence on women given the same memory task. These results suggest that DDAVP may have a sexually dimorphic effect on learning and memory.     

Successful treatment of partial nephrogenic diabetes insipidus with thiazide and desmopressin

OBJECTIVE: To clarify whether combination treatment with desmopressin (DDAVP) and thiazide was clinically effective in a patient with congenital nephrogenic diabetes insipidus (CNDI), we evaluated the treatment in a 7-year-old boy with CNDI who had demonstrated a partial response to DDAVP. METHOD: Both volume of urine and the presence of nocturia were determined during treatment. RESULT: Neither the usual therapy of a low-salt diet and a thiazide nor intranasal therapy with a large dose of DDAVP was effective. However, combination treatment resulted in a decrease in urinary volume and the disappearance of nocturia. CONCLUSION: DDAVP coupled with thiazide may be useful for CNDI in patients who have shown a partial response to DDAVP.     

Spinal manipulative therapy and somatosensory activation

Manually-applied movement and mobilization of body parts as a healing activity has been used for centuries. A relatively high velocity, low amplitude force applied to the vertebral column with therapeutic intent, referred to as spinal manipulative therapy (SMT), is one such activity. It is most commonly used by chiropractors, but other healthcare practitioners including osteopaths and physiotherapists also perform SMT. The mechanisms responsible for the therapeutic effects of SMT remain unclear. Early theories proposed that the nervous system mediates the effects of SMT. The goal of this article is to briefly update our knowledge regarding several physical characteristics of an applied SMT, and review what is known about the signaling characteristics of sensory neurons innervating the vertebral column in response to spinal manipulation. Based upon the experimental literature, we propose that SMT may produce a sustained change in the synaptic efficacy of central neurons by evoking a high frequency, bursting discharge from several types of dynamically-sensitive, mechanosensitive paraspinal primary afferent neurons.     

Imino sugar inhibitors for treating the lysosomal glycosphingolipidoses

The inherited metabolic disorders of glycosphingolipid (GSL) metabolism are a relatively rare group of diseases that have diverse and often neurodegenerative phenotypes. Typically, a deficiency in catabolic enzyme activity leads to lysosomal storage of GSL substrates and in many diseases, several other glycoconjugates. A novel generic approach to treating these diseases has been termed substrate reduction therapy (SRT), and the discovery and development of N-alkylated imino sugars as effective and approved drugs is discussed. An understanding of the molecular mechanism for the inhibition of the key enzyme in GSL biosynthesis, ceramide glucosyltransferase (CGT) by N-alkylated imino sugars, has also lead to compound design for improvements to inhibitory potency, bioavailability, enzyme selectivity, and biological safety. Following a successful clinical evaluation of one compound, N-butyl-deoxynojirimycin [(NB-DNJ), miglustat, Zavesca], for treating type I Gaucher disease, issues regarding the significance of side effects and CNS access have been addressed as exposure of drug to patients has increased. An alternative experimental approach to treat specific glycosphingolipid (GSL) lysosomal storage diseases is to use imino sugars as molecular chaperons that assist protein folding and stability of mutant enzymes. The principles of chaperon-mediated therapy (CMT) are described, and the potential efficacy and preclinical status of imino sugars is compared with substrate reduction therapy (SRT). The increasing use of imino sugars for clinical evaluation of a group of storage diseases that are complex and often intractable disorders to treat has considerable benefit. This is particularly so given the ability of small molecules to be orally available, penetrate the central nervous system (CNS), and have well-characterized biological and pharmacological properties.     

Time course of a repetition effect on saccadic reaction time in non-human primates

Repeated training in a stimulus response task can lead to adaptive changes in the resulting behavior. Using a simple saccade task, we investigated the effect that the location of the target in the preceding trial had on the saccadic reaction time (SRT) of the current trial. To determine the time course of this effect, we varied the intertrial interval (ITI). Finally, we examined the pretarget discharge of single neurons in the intermediate layers of the superior colliculus (SC) during the task. Our data reveal that monkeys have a robust repetition effect in which there was an overall decrease in SRT and increase in SC pretarget activity when the target of the previous saccade was in the same location as that of the current trial. Additionally, we have shown a robust time course of this repetition effect, revealing that it exists for only a limited amount of time.     

Accuracy and precision of a wrist movement when vibrotactile prompts inform movement speed

Abstract

Purpose: This study investigated the effect of movement speed on task accuracy and precision when participants were provided temporally oriented vibrotactile prompts. Materials and methods: Participants recreated a simple wrist flexion/extension movement at fast and slow speeds based on target patterns conveyed via vibrating motors affixed to the forearm. Each participant was given five performance-blinded trials to complete the task at each speed. Movement accuracy (root mean square error) and precision (standard deviation) were calculated for each trial in both the spatial and temporal domains. Results: 28 participants completed the study. Results showed temporal accuracy and precision improved with movement speed (both: fast?>?slow, p?<?0.01), while all measures improved across trials (temporal accuracy and precision: trial 1?<?all other trials, p?<?0.05; spatial accuracy: trial 1 and 2?<?all other trials, p?<?0.05; spatial precision: trial 1?<?all other trials, p?<?0.05). Conclusions: Overall, temporal and spatial results indicate participants quickly recreated and maintained the desired pattern regardless of speed. Additionally, movement speed seems to influence movement accuracy and precision, particularly within the temporal domain. These results highlight the potential of vibrotactile prompts in rehabilitation paradigms aimed at motor re-education.     

Stereotactic radiotherapy for oligometastases in the lymph nodes

Even though systemic therapy is standard treatment for lymph node metastases, metastasis-directed stereotactic radiotherapy (SRT ) seems to be a valid option in oligometastatic patients with a low disease burden.Positron emission tomography-computed tomography (PET-CT ) is the gold standard for assessing metastases to the lymph nodes; co-registration of PET-CT images and planning CT images are the basis for gross tumor volume (GTV ) delineation. Appropriate techniques are needed to overcome target motion. SRT schedules depend on the irradiation site, target volume and dose constraints to the organs at risk (OARs) of toxicity. Although several fractionation schemes were reported, total doses of 48–60 Gy in 4–8 fractions were proposed for mediastinal lymph node SRT, with the spinal cord, esophagus, heart and proximal bronchial tree being the dose limiting OAR s. Total doses ranged from 30 to 45 Gy, with daily fractions of 7–12 Gy for abdominal lymph nodes, with dose limiting OARs being the liver, kidneys, bowel and bladder. SRT on lymph node metastases is safe; late side effects, particularly severe, are rare.     

Relationship between the dose of 1-deamino-8-d-arginine vasopressin (ddavp) and the antidiuretic response in man.

A definite relationship was found between the dose of DDAVP (1-24 mug intravenously and 5-320 mug intranasally) and the antidiuretic effects (expressed in changes in free water clearance per 100 ml GFR and in urine osmolality determined in 24 hour urine collection periods) in 7 patients with diabetes insipidus. The relationship was more conspicuous when the second 12 hour antidiuretic responses were considered, indicating a dose-dependent prolongation of the antidiuretic action. Time-curves of the antidiuretic responses proved the dose-dependent prolongation of the duration of antidiuretic action. Second 12 hour antidiuretic response increased more markedly when DDAVP was given divided in two doses a day as compared to the effects of the same quantity of the drug given as a single dose; only by the administration of excessive single doses the effects of the divided doses could be reproduced.     

Right- and left-brain hemisphere. Rhythm in reaction time to light signals is task-load-dependent: age,gender, and handgrip strength rhythm comparisons

In healthy mature subjects simple reaction time (SRT) to a single light signal (an easy task) is associated with a prominent rhythm with tau = 24 h of dominant (DH) as well as nondominant (NDH) hand performance, while three-choice reaction time (CRT), a complex task, is associated with tau = 24 h of the DH but tau < 24 h of the NDH. The aims of the study were to assess the influence of age and gender on the difference in tau of the NDH and DH, as it relates to the corresponding cortical hemisphere of the brain, in comparison to the rhythm in handgrip strength. Healthy subjects, 9 (5 M and 4 F) adolescents 10-16 yr of age and 15 (8 M and 7 F) adults 18-67 yr of age, active between 08:00 +/- 1 h and 23:00 +/- 1:30 h and free of alcohol, tobacco, and drug consumption volunteered. Data were gathered longitudinally at home and work 4-7 times daily for 11-20 d. At each test time the following variables were assessed: grip strength of both hands (Dynamometer: Colin-Gentile, Paris, France); single reaction time to a yellow signal (SRT); and CRT to randomized yellow, red, or green signal series with varying instruction from test to test (Psycholog-24: Biophyderm, France). Rhythms in the performance in SRT, CRT, and handgrip strength of both DH and NDH were explored. The sleep-wake rhythm was assessed by sleep-logs, and in a subset of 14 subjects it was also assessed by wrist actigraphy (Mini-Motionlogger: AMI, Ardsley NY). Exploration of the prominent period tau of time series was achieved by a special power spectra analysis for unequally spaced data. Cosinor analysis was used to quantify the rhythm amplitude A and rhythm-adjusted mean M of the power spectral analysis determined trial tau. A 24h sleep-wake rhythm was detected in almost all cases. In adults, a prominent tau of 24 h characterized the performance of the easy task by both the DH and NDH. In adults a prominent tau of 24 h was also detected in the complex CRT task performed by the DH, but for the NDH the tau was < 24 h. This phenomenon was not gender-related but was age-related since it was seldom observed in adolescent subjects. Hand-side differences in the grip strength rhythms in the same individuals were detected, the tau being ultradian rather than circadian in adolescent subjects while in mature subjects the tau frequently differed from that of the rhythm in CRT. These findings further support the hypothesis that functional biological clocks exist in both the left and right hemispheres of the human cortex.     

Vasopressin Analogue DDAVP in Diabetes Insipidus: Clinical and Laboratory Studies

In seven patients with cranial diabetes insipidus an analogue of vasopressin, DDAVP, produced an antidiuresis lasting up to 20 hours after a single intranasal dose. Lysine vasopressin (LVP) in the same dose produced a less potent antidiuresis which lasted for only three to four hours. The plasma half life of DDAVP was 7·8 and 75·5 min for the fast and slow phases, compared with 2·5 and 14·5 min for LVP. Radioiodine-labelled DDAVP was not destroyed by incubation with late pregnancy plasma, which contains an enzyme that inactivates vasopressin. The slow metabolic clearance of DDAVP, its absorption through the nasal mucosa, and its lack of side effects make this the ideal drug for the treatment of vasopressin-sensitive diabetes insipidus. Patients usually require 10 to 20 μg DDAVP given intranasally twice daily for good clinical control of their diabetes insipidus.     

Altered endogenous negativities of the visual event-related potential in remitted schizophrenia

Visual event-related potentials (ERPs) were recorded during a simple response task (SRT) and a discriminative response task (DRT) in remitted schizophrenic outpatients and age-matched controls to examine 2 endogenous negative potentials: NA and N2c. The NA potentials were derived by subtracting the ERPs for SRT from those for non-target stimuli in DRT. Other subtracting wave forms, N2c potentials, were calculated as the difference between ERPs for target and non-target stimuli in DRT. Schizophrenics showed retardation in NA and N2c peaks and degradation in N2c amplitude relative to controls. The NA peak latency increased as much as the latencies of N2c and reaction time for DRT in schizophrenia. The NA peak emerged prior to the N2c peak, while the NA peak latency correlated closely with the N2c latency. These results indicate that the retarded NA peak latency may serve as a physiological marker for neurobiological vulnerability of schizophrenia.     

Fast visual categorization and speed of processing in migraine]

It has been suggested that the visual cortex of migraine sufferers is hypersensitive. To test this hypothesis, we compared the speed of visual processing in eight migraine patients (including three with aura) and nine controls performing two categorisation tasks of different complexity. In the complex task developed by Thorpe et al. (1996), subjects had to detect the presence of animals in briefly presented photographs (20 ms). The speed of visual processing was measured by the latency of the differential cerebral activity that appears around 150 ms between target and non-target trials. In the simple task, subjects performed a square/circle categorisation. All subjects were faster (445 ms/497 ms) with a higher rate of success (97%/91%) in the simple task. But in both tasks, the behavioural performance and the associated evoked potentials did not show any difference suggesting a cortical hypersensitivity in migraine sufferers.     

Absorption of intragastrically administered DDAVP in conscious dogs

Plasma concentrations of DDAVP were measured after intragastric administration and intravenous infusion in dogs. Oral ingestion of DDAVP led to a dose dependent increase in peak plasma concentrations as well as area under the curve (AUC). Intravenous infusion of DDAVP (0.13 pmol/l min) resulted in a mean steady-state level of 20.3 pmol/l. Elimination half-lives for oral DDAVP were 77.6 and 76.1 min for low and high doses respectively. T1/2 estimated from the ascending part of the i.v. infusion curve was 50 min. A metabolic clearance rate (MCR) of 3.9 ml/kg . min was assessed from the i.v. steady-state level.     

Characterising Upper Limb Movements in Huntington's Disease and the Impact of Restricted Visual Cues

Background

Voluntary motor deficits are a common feature in Huntington''s disease (HD), characterised by movement slowing and performance inaccuracies. This deficit may be exacerbated when visual cues are restricted.

Objective

To characterize the upper limb motor profile in HD with various levels of difficulty, with and without visual targets.

Methods

Nine premanifest HD (pre-HD), nine early symptomatic HD (symp-HD) and nine matched controls completed a motor task incorporating Fitts'' law, a model of human movement enabling the quantification of movement timing, via the manipulation of task difficulty (i.e., target size, and distance between targets). The task required participants to make reciprocal movements under cued and blind conditions. Dwell times (time stationary between movements), speed, accuracy and variability of movements were compared between groups.

Results

Symp-HD showed significantly prolonged and less consistent movement times, compared with controls and pre-HD. Furthermore, movement planning and online control were significantly impaired in symp-HD, compared with controls and pre-HD, evidenced by prolonged dwell times and deceleration times. Speed and accuracy were comparable across groups, suggesting that group differences observed in movement time, variability, dwell time and deceleration time were evident over and above simple performance measures. The presence of cues resulted in greater movement time variability in symp-HD, compared with pre-HD and controls, suggesting that the deficit in movement consistency manifested only in response to targeted movements.

Conclusions

Collectively, these findings provide evidence of a deficiency in both motor planning, particularly in relation to movement timing and online control, which became exacerbated as a function of task difficulty during symp-HD stages. These variables may provide a more sensitive measure of motor dysfunction than speed and/or accuracy alone in symp-HD.