Neither Cathodal nor Anodal Transcranial Direct Current Stimulation on the Left Dorsolateral Prefrontal Cortex alone or Applied During Moderate Aerobic Exercise Modulates Executive Function.

There is converging evidence that both aerobic exercise (AE) and transcranial direct current stimulation (tDCS) can acutely modulate executive functions (EF). In addition, recent studies have proposed the beneficial effects of applying tDCS during AE on physical performance. This study aimed to investigate whether tDCS applied during an AE session additionally or differently effects EF. Therefore, five experiments were conducted in a counterbalanced pre-post-retention crossover design to explore the acute effects of tDCS and AE on EF (inhibition and updating) once in isolation (i.e., either cathodal, anodal tDCS or AE alone as controls) and once in a combined application (i.e., anodal and cathodal tDCS during AE versus sham tDCS during AE). No differences were found in any experiment in the cognitive test parameters. However, in the case of anodal tDCS vs. sham during AE, heart rate was significantly affected. For cathodal tDCS vs. sham during AE, a significant Anova interaction indicated that cathodal tDCS during AE slightly reduced ratings of perceived exertion. The nonsignificant effects of tDCS on EFs are in contrast to previous studies, as no replication of existing observations could be achieved. Thus, the protocol applied in this study does not provide any strong evidence that a combination of AE and tDCS has any effects on EFs, but indicates effects on physiological parameters and subjective exhaustion ratings. Further research should consider changes in AE and tDCS parameters (e.g., intensity or exercise mode) and sequence of applications (online vs. offline).

Serum adiponectin levels are significantly reduced during the second half of normal pregnancy.

PURPOSE: To demonstrate the physiologic changes in adiponectin levels during the first vs second half of pregnancy. METHODS: Sixty-six females with uncomplicated pregnancies and normal pre-gestational BMI had serum adiponectin levels obtained at various gestational ages. Thirty-one samples were obtained during the first half of their pregnancy vs 35 in the second half. Thirty-three healthy non-pregnant females with comparable ages and BMI were controls. RESULTS: Mean adiponectin levels were 9.55 microg/dl (95% CI 8.2-10.77) vs 9.48 microg/dl (95% CI 8.44-10.66) in the control group in the first half of pregnancy (p = NS). We noted a 21% reduction in mean adiponectin levels (7.51 microg/dl) during the second half of pregnancy (p = 0.03) compared to the first half of pregnancy. CONCLUSION: Early pregnancy does not affect adiponectin levels. However, there is a significant reduction in adiponectin levels during the second half of pregnancy.

Potential pharmacokinetic basis for zolpidem dosing in children with sleep difficulties.

The pharmacokinetics of zolpidem was assessed in this open-label, dose-escalation study in children with insomnia. Twenty-one children, seven per age group (2-6, >6 to 12, >12 to 18 years), received a single dose of zolpidem at one of the three dose levels (0.125, 0.25, or 0.50 mg/kg (20 mg maximum dose)). Multiple pharmacokinetic measures were assessed at nine post-dose intervals and pharmacodynamics was assessed by polysomnography and actigraphy. Significant pharmacokinetic effects by dose were observed only as linear increases in maximum concentration (C(max), P<0.001) and area under the plasma concentration-time curve (AUC, P<0.001). Significant pharmacokinetic effects by age group included an increase in AUC (P=0.02), half-life (P=0.04), and mean residence time (P=0.01), whereas total body clearance decreased (P=0.01) and steady-state volume of distribution was variable. Pharmacodynamic measures were independent of the pharmacokinetic estimates. Overall, zolpidem was well tolerated and a pediatric dose of 0.25 mg/kg is recommended for future efficacy studies.

Repeated botulinum toxin injections can improve mobility in patients with spinal cord lesions.

AIM: The aim of this study was to increase the knowledge about the response to botulinum toxin (BTX) injections to spastic leg muscle motor points (MP) in spinal cord lesion (SCL) patients, and describe improvement of mobility with repeated BTX injections. METHODS: Six patients with ASIA grade C or D SCL were studied at the Loewenstein Rehabilitation Center, Israel. The main outcome measures were: modified Ashworth scale scores, range of motion (ROM), and mobility spinal cord independence measure (SCIM) scores. BTX was injected twice within a few weeks' interval to the MP of spastic leg muscles. The outcome measures were monitored before each injection and 2 weeks or more after the second injection. RESULTS: Following the first BTX injection the tonus decreased, ROM increased in all 6 patients, and mo- bility functioning improved in 4 of them. Following the repeated injection the tonus further decrea- sed, ROM further improved in 5 of 6 patients, and mobility functions further improved in 4 of 6 patients. CONCLUSION: BTX can improve mobility in patients with SCL. Repeated injections may enhance the effect despite the concern for resistance formation. Further research is needed to support the findings and determine the optimal BTX doses and intervals between injections.

Electromyographic signal-activated functional electrical stimulation of abdominal muscles: the effect on pulmonary function in patients with tetraplegia.

BACKGROUND: Paralysis of abdominal muscles is the main cause of respiratory dysfunctions in patients with lower cervical spinal cord lesion. Activation of the abdominal muscles using functional electrical stimulation (FES) improved respiratory function in these patients. But application of FES frequently requires a caregiver, and it may not be well synchronized with the patient's respiratory activity. OBJECTIVE: To perform preliminary examination of electromyographic (EMG)-activated FES for caregiver-independent and synchronized cough and expiration induction in tetraplegia. DESIGN: Self-controlled study. SETTING: Loewenstein Rehabilitation Center, Raanana, Israel. SUBJECTS: A total of 10 male patients with complete or almost complete tetraplegia. MAIN OUTCOME MEASURES: Peak expiratory flow (PEF), forced vital capacity (FVC), and maximal voluntary ventilation (MVV). METHODS: The outcome measures were examined with the abdominal muscles unassisted or assisted by various methods. These included manual assistance or application of FES, activated by a caregiver, by the patient, or by EMG signals elicited from the patient's muscle. RESULTS: Manual assistance improved the mean PEF value by 36.7% (P<0.01) and the mean FVC value by 15.4% (P=0.01). FES did not significantly change most measurements, and patient-activated FES even reduced PEF (P<0.05). But following EMG-activated FES PEF and FVC values were higher than those following patient-activated FES (P<0.05 for PEF; P<0.01 for FVC), and their mean values were higher by 15.8 and 18.9%, respectively. CONCLUSIONS: Abdominal FES failed to improve respiratory function in this study, but applying FES to abdominal muscles by EMG from the patient's muscle may promote caregiver-free respiration and coughing in persons with cervical SCL.

A parametric fMRI investigation of context effects in sensorimotor timing and coordination.

Mounting evidence suggests that information derived from environmental and behavioral sources is represented and maintained in the brain in a context-dependent manner. Here we investigate whether activity patterns underlying movements paced according to an internal temporal representation depend on how that representation is acquired during a previous pacing phase. We further investigate the degree to which context dependence is modulated by different time delays between pacing and continuation. BOLD activity was recorded while subjects moved at a rate established during a pacing interval involving either synchronized or syncopated coordination. Either no-delay or a 3, 6 or 9s delay was introduced prior to continuation. Context-dependent regions were identified when differences in neural activity generated during pacing continued to be observed during continuation despite the intervening delay. This pattern was observed in pre-SMA, bilateral lateral premotor cortex, bilateral declive and left inferior semi lunar lobule. These regions were more active when continuation followed from syncopation than from synchronization regardless of the delay length putatively revealing a context-dependent neural representation of the temporal interval. Alternatively, task related regions in which coordination-dependent differences did not persist following the delay, included bilateral putamen and supplementary-motor-area. This network may support the differential timing demands of coordination. A classic prefrontal-parietal-temporal working memory network was active only during continuation possibly providing mnemonic support for actively maintaining temporal information during the variable delay. This work provides support for the hypothesis that some timing information is represented in a task-dependent manner across broad cortical and subcortical networks.

Assessing recovery in middle cerebral artery stroke using functional MRI.

PRIMARY OBJECTIVE: To understand the temporal evolution of brain reorganization during recovery from stroke. RESEARCH DESIGN: A patient who suffered left middle cerebral artery stroke 9 months earlier was studied on three occasions, approximately 1 month apart. METHODS AND PROCEDURES: Brain activation was studied using functional Magnetic Resonance Imaging (fMRI). During each session, the patient performed a finger-to-thumb opposition task, which involved one bimanual and two unimanual conditions. Each condition consisted of overt movement of fingers and imagery of the same task. RESULTS: With recovery, greater recruitment was observed of the affected primary motor cortex (M1) and a decrease in activation of the unaffected M1 and supplementary motor area. In addition, the widespread activation of brain areas seen during the initial session changed to a more focused pattern of activation as the patient recovered. Imagery tasks resulted in similar brain activity as overt execution pointing to imagery as a potential tool for rehabilitation.

Animal models and analytical approaches for understanding the relationships between wine and cancer.

We used two approaches for studying the relationships between wine consumption, wine composition and cancer In the first approach, a transgenic mouse model of human neurofibromatosis, combined with the use of well-defined, chemically purified diets, showed that red wine contains nonalcoholic components that can delay tumor onset. In additional studies, catechin, the main monomeric polyphenol of red wine, delayed tumor onset in this mouse model in a positive, linear relationship when incorporated into the diet at levels of 0.5-4 mmol/kg diet. In the second approach, low doses of the chemical carcinogen 2-amino-1-methyl-6-phenylimidazo(4, 5-b)pyridine (PhlP) were administered to rats, and formation of DNA adducts was evaluated by accelerator mass spectrometry. Consumption of red wine solids (the residue from red wine remaining after removal of alcohol and water) and the wine polyphenol quercetin did not influence PhlP-DNA adduct levels or induce liver enzymes (glutathione-S-transferase and quinone reductase). However, quercetin did alter distribution of PhlP in the rat tissues compared to control animals and animals fed other potential dietary chemopreventive agents, including phenylethyl isothiocyanate and sulforaphane. These studies demonstrate the feasibility of these approaches for studying the chemopreventive potential of dietary components at physiologic levels in

Functional MRI reveals the existence of modality and coordination-dependent timing networks.

Growing evidence suggests that interval timing in humans is supported by distributed brain networks. Recently, we demonstrated that the specific network recruited for the performance of rhythmic timing is not static but is influenced by the coordination pattern employed during interval acquisition. Here we expand on this previous work to investigate the role of stimulus modality and coordination pattern in determining the brain areas recruited for performance of a self-paced rhythmic timing task. Subjects were paced with either a visual or an auditory metronome in either a synchronized (on the beat) or syncopated (off the beat) coordination pattern. The pacing stimulus was then removed and subjects continued to move based on the required interval. When compared with networks recruited for auditory pacing and continuation, the visual-specific activity was observed in the classic dorsal visual stream that included bilateral MT/V5, bilateral superior parietal lobe, and right ventral premotor cortex. Activity in these regions was present not only during pacing, when visual information is used to guide motor behavior, but also during continuation, when visual information specifying the temporal interval was no longer present. These results suggest a role for modality-specific areas in processing and representing temporal information. The cognitive demands imposed by syncopated coordination resulted in increased activity in a broad network that included supplementary motor area, lateral pre-motor cortex, bilateral insula, and cerebellum. This coordination-dependent activity persisted during the subsequent continuation period, when stimuli were removed and no coordination constraints were imposed. Taken together, the present results provide additional evidence that time and timing are served by a context-dependent distributed network rooted in basic sensorimotor processes.

Neural substrates of real and imagined sensorimotor coordination.

Much debate in the behavioral literature focuses on the relative contribution of motor and perceptual processes in mediating coordinative stability. To a large degree, such debate has proceeded independently of what is going on in the brain. Here, using blood oxygen level-dependent measures of neural activation, we compare physically executed and imagined rhythmic coordination in order to better assess the relative contribution of hypothesized neuromusculoskeletal mechanisms in modulating behavioral stability. The executed tasks were to coordinate index finger to thumb opposition movements of the right hand with an auditory metronome in either a synchronized (on the beat) or syncopated (off the beat) pattern. Imagination involved the same tasks, except without physical movement. Thus, the sensory stimulus and coordination constraints were the same in both physical and imagination tasks, but the motoric requirements were not. Results showed that neural differences between executed synchronization and syncopation found in premotor cortex, supplementary motor area, basal ganglia and lateral cerebellum persist even when the coordinative patterns were only imagined. Neural indices reflecting behavioral stability were not abolished by the absence of overt movement suggesting that coordination phenomena are not exclusively rooted in purely motoric constraints. On the other hand, activity in the superior temporal gyrus was modulated by both the presence of movement and the nature of the coordination, attesting to the intimacy between perceptual and motoric processes in coordination dynamics.

Body composition in the elderly: the influence of nutritional factors and physical activity.

BACKGROUND: Controversy exists regarding the relative contribution of diet and exercise to body composition. Few studies have examined these associations in the elderly, where changes occur in the body fat to muscle ratio. OBJECTIVE: The primary objective of this paper is to determine whether energy intake or physical activity are associated with body composition. Secondly, to investigate whether specific macronutrients are associated with fat or lean tissue. DESIGN: Data (n= 1404) for this cross-sectional analysis were collected from a population-based sub-sample of elderly enrollees in the Cardiovascular Health Study (CHS). Dietary intake and physical activity were assessed by questionnaires. Body composition was measured by Dual Energy X-ray Absorptiometry (DEXA). Linear regression models were used to assess the associations of diet and activity with body composition. RESULTS: Total energy intake was not associated with any of the body composition measures. Higher dietary saturated fat was associated with higher percent body mass as fat and trunk fat in both sexes (p<0.01), and in men other dietary fats were associated with body fat. In women, distance walked was inversely associated with fat masses even after adjustment for pace of walking. In both sexes, faster pace of walking was associated with lower body and fat mass (p<0.01). Lean muscle mass was not associated with physical activity or dietary intakes. CONCLUSION: Physical activity and dietary fat intake in this the elderly population were more closely associated with body fat mass than was total energy intake.

Practice-dependent modulation of neural activity during human sensorimotor coordination: a functional Magnetic Resonance Imaging study.

We investigated the degree to which differences in the pattern of blood oxygen level dependent activity (BOLD) between syncopated and synchronized coordination patterns are altered by practice. Baseline levels of BOLD activity were obtained from eight subjects while they syncopated or synchronized with an auditory metronome at 1.25 Hz. Subjects then practiced syncopation at the same rate for four consecutive sessions. Post practice scans of the two coordination patterns were then performed. Before practice, baseline syncopation activated a much broader network of both cortical and subcortical regions than synchronization that included Supplementary Motor Area (SMA), bilateral putamen, left thalamus, bilateral superior temporal gyrus as well as the vermis. This pattern of activity is hypothesized to reflect the extra timing and attention requirements of syncopation. After practice, activity in superior temporal gyrus and vermis were no longer observed during syncopation reflecting a reduction in the need for attention and the use of sensory feedback for guiding behavior. Surprisingly, post practice synchronization resulted in additional significant activations in SMA, inferior frontal gyrus and superior temporal gyrus as well as small activations in bilateral putamen. Practice with the more difficult syncopation task thus had a dual effect of decreasing the number of active regions during syncopation and increasing the number of active regions during synchronization. Since overt syncopation performance did not change significantly as a result of practice, these observed neural changes appear to be due to context- and history-dependent factors, rather than behavioral learning per se.

Walnut polyphenolics inhibit in vitro human plasma and LDL oxidation.

Recent epidemiologic studies have associated nut consumption with a reduced incidence of cardiovascular mortality. However, little is known about the contribution of nut polyphenols to antioxidant and cardiovascular protection. In this investigation, polyphenol-rich extracts from English walnuts (Juglans regia) were studied and compared with ellagic acid for their ability to inhibit in vitro plasma and LDL oxidation, as well as their effects on LDL alpha-tocopherol during oxidative stress. In addition, the Trolox equivalent antioxidant activity (TEAC) was determined and liquid chromatography electrospray detection mass spectrometry (LC-ELSD/MS) analyses of the walnut extracts were performed. 2,2'-Azobis'(2-amidino propane) hydrochloride (AAPH)-induced LDL oxidation was significantly inhibited by 87 and 38% with the highest concentration (1.0 micromol/L) of ellagic acid and walnut extract, respectively. In addition, copper-mediated LDL oxidation was inhibited by 14 and 84% in the presence of ellagic acid and walnut extract, respectively, with a modest, significant LDL alpha-tocopherol sparing effect observed. Plasma thiobarbituric acid reacting substance (TBARS) formation was significantly inhibited by walnut extracts and ellagic acid in a dose-dependent manner, and the extracts exhibited a TEAC value greater than that of alpha-tocopherol. LC-ELSD/MS analysis of the walnut extracts identified ellagic acid monomers, polymeric ellagitannins and other phenolics, principally nonflavonoid compounds. These results demonstrate that walnut polyphenolics are effective inhibitors of in vitro plasma and LDL oxidation. The polyphenolic content of walnuts should be considered when evaluating their antiatherogenic potential.

The Catz-Itzkovich SCIM: a revised version of the Spinal Cord Independence Measure.

PURPOSE: To examine the suitability of the revised Spinal Cord Independence Measure, the Catz-ltzkovich SCIM, for evaluation of patients with spinal cord lesions, as compared to the original SCIM and to the Functional Independence Measure (FIM). METHOD: The revised SCIM was applied by paired independent teams of occupational therapists, physiotherapists and nurses and the FIM by a single nurse. The examiners assigned scores to the functional capabilities of 28 patients with spinal cord lesions. The scores by the revised SCIM were analysed for reproducibility as between the two teams of examiners (interrater reliability) and for their correlation with the FIM scores. RESULTS: The frequency of identical scoring by two independent examiners (total agreement) was 80% or higher for 13/18 individual functions listed in the revised SCIM. In the self-care category it was 80-99%, as compared to 75-87% before revision. In neither bowel management nor bed mobility was there an increase over the original SCIM in the frequency of identical scores, despite rephrasing and restructuring of the scoring criteria. A high correlation was noted between the paired scores for all functions listed as well as for those comprising each of the four functional categories (r = 0.90-0.96, p <0.001). The total revised-SCIM scores were significantly correlated with those derived by the FIM (r = 0.835, p < 0.001). CONCLUSIONS: The findings indicate that the newly revised SCIM (Catz-Itzkovich) is a valid and highly reproducible measure of daily function in patients with spinal cord lesions, and is superior to the original SCIM. We recommend that it supersede the original SCIM.

Spinal pain independence measure--a new scale for assessment of primary ADL dysfunction related to LBP.

PURPOSE/METHOD: SPIM Spinal Pain Independence Measure. a new disability scale designed for patients with chronic low back pain disability, has been developed and studied at the Spinal Department of Loewenstein Rehabilitation Hospital. The SPIM differs from other existing scales for evaluation of chronic back disability, in that it is designated particularly for patients with deficits in primary ADL and evaluates function by observation. RESULTS/CONCLUSIONS: This study shows the SPIM to be reliable: it supports the validity of the scale and points out a possible advantage of the SPIM over existing scales in sensitivity to functional change of patients with prominent disability. Further elaboration and examination of the SPIM is still needed.

Influence of oligomer chain length on the antioxidant activity of procyanidins.

The antioxidant activity of catechin monomers and procyanidin (dimers to hexamers) fractions purified from cocoa was studied in two in vitro systems: liposomes and human LDL. Liposome oxidation (evaluated as formation of 2-thiobarbituric acid reactive substances) was initiated with 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH), 2,2'-azobis (2,4-dimethylvaleronitrile) (AMVN), iron/ascorbate, or UV-C; LDL oxidation (evaluated as formation of conjugated dienes) was initiated with Cu(2+) or AAPH. Catechin monomers and procyanidin fractions inhibited both liposome and LDL oxidation. Monomers, dimers, and trimers fractions were the most effective antioxidants when liposome oxidation was initiated in the aqueous phase. When oxidation was initiated in the lipid domains, higher molecular weight procyanidins were the most effective. All fractions significantly inhibited Cu-mediated LDL oxidation; no significant effect of procyanidin molecular weight was observed. The hexamer fraction was the least effective with respect to preventing AAPH initiated LDL oxidation. Results reported herein give further evidence on the influence of the oligomer chain length on the antioxidant protection by procyanidins.