Silent period to transcranial magnetic stimulation: construction and properties of stimulus–response curves in healthy volunteers

Silent period (SP) is widely used in transcranial magnetic stimulation studies. Methodologically, SP is usually elicited at stimulus intensities corresponding to a certain percentage of corticomotor threshold. Because this approach might lead to factitious SP changes, the present study was designed to develop, in a stepwise manner, a method for investigating SP independently of corticomotor threshold. First, stimulus–response (S–R) curves of SP against stimulus intensity (SI) were constructed and quantitatively described in healthy volunteers. Second, various methodological issues such as the optimum model for describing the relationship between SP duration and SI and the importance of the type of stimulating coil were addressed. Finally, the proposed method and a commonly used method (eliciting SPs at 130% MT SI) were directly compared for a group of epileptic patients for whom administration of oxcarbazepine resulted in significant corticomotor threshold elevation. Twenty-one subjects (eleven females, median age, 38 years) were studied. SPs were obtained with a figure-of-eight coil using a standardized procedure (recording, FDI). Pilot experiments indicated that at least four trials were required, at each intensity level, to estimate the mean SP duration within 10% of the true mean. Therefore, SPs were determined from the average of four trials with 5% increments from 5 to 100% maximum SI. In a second set of experiments, SPs were obtained for fifteen subjects using a circular coil. In a third set of experiments, eight epileptic patients were studied before and after administration of oxcarbazepine (mean dose 1553 mg, range 900–1800 mg). The S–R curves were fitted to a Boltzman function and to first-order to fourth-order polynomial and sigmoid functions. The Boltzman function described the data accurately (R²=0.947–0.990). In addition, direct comparison of the six models with an F-test proved the superiority of the first. The best-fit parameters of the reference curve, i.e. the maximum and minimum values, the slope, and V₅₀ (the SI at which SP duration is halfway between Min and Max) were 230.8±3.31 ms (x±SEM), –11.51±3.31 ms, 11.56±0.65%, and 49.82±0.65%, respectively. When the curves obtained with the circular coil were compared with those obtained with the figure-of-eight coil, there were differences between V₅₀ (51.69±0.72 vs 47.95±0.82, P<0.001) and SP threshold (31.15 vs 24.77, P<0.01) whereas the other best-fit values did not differ significantly. Oxcarbazepine increased corticomotor threshold from 45.3±5.8% at baseline to 59.4±10.4% (P<0.001). According to the commonly used method, the drug significantly prolonged SP (from 117.6±42.4 ms to 143.5±46.5 ms, P<0.001) and, consequently, enhanced brain inhibition. In contrast, study of the SP curves led to the conclusion that oxcarbazepine does not affect the Max value and slope but significantly increases V₅₀ and SP threshold (from 54.5±4.9% to 59.9±7.2% and from 29.1±6.4% to 34.6±6.8%, respectively, P<0.01). These findings imply that oxcarbazepine does not enhance brain inhibitory mechanisms. Thus, in situations characterized by significant changes in corticomotor threshold the proposed method provides results clearly different from a commonly used approach. It is concluded that S–R curves obtained with a figure-of-eight coil in 5% increments and fitted to a Boltzman function provide an accurate, comprehensive, and clinically applicable method for exploring SP.Presented in part at the meeting of the EFNS, Helsinki, September 2003     

Model identification and estimation of organ-function parameters using radioactive tracers and the impulse-response function

Examination of the input-output events in functioning organs by the use of the impulse-response function (IRF) for a radioactive tracer is gaining more and more ground in nuclear medicine. This study summarizes the development of deconvolution analysis, laying special stress on the model-free approach. System linearity and time invariance are discussed, and means of eliminating noise in IRFs originating from the input and organ-time-activity curves are outlined. Typical IRFs are illustrated by flow diagrams, time-domain curves, and their representation by Laplace transforms. The cases of nondiffusible and diffusible tracers as well as parenchymally extracted and transported substances are discussed. Methods for the derivation of models and for the calculation of physiologically important parameters from theIRFs are suggested.At present, a guest scientist at the Institute for Medicine, Nuclear Research Center Jülich, Jülich, Federal Republic of Germany     

Left ventricular function following withdrawal of chronic metoprolol treatment in patients with ischaemic heart disease. A double blind study

The effect on left ventricular function of a gradual withdrawalof chronic metoprolol treatment in postinfarction patients wasstudied. All patients were in a randomized double-blind post-infarctionstudy with metoprolol (M 100–200 mg daily; N=14) or placebo(P; N =18). After three years treatment the study medicationwas gradually withdrawn during one week. M-mode echocardiography,guided by concomitant cross-sectional recordings, were performedbefore, one and 12 weeks after the withdrawal. Treatment (i.e.M or P) had to be reinstituted in eight patients (5 M; 3P) becauseof the development of disabling symptoms during the follow-up.Heart rate was lower in patients treated with M (57±4)than with P (69±10) (p<0.01). One week after withdrawalof M, heart rate had increased to 77± 13(p<0.001),while patients on P showed no significant change. In order tominimize the influence of heart rate on the evaluation of timeintervals in the cardiac cycle, heart rate dependent correctionfactors were used. One week after M withdrawal there was a prolongationof the pre-ejection period (PEP) from 120±15 ms to 133±16ms (p< 0.01), mainly due to a prolongation of the intervalfor early isovolumetric contraction (Q Mc) from 87±10ms to 101±11 ms (N=11; p0.001). Simultaneously, valuesfor isovolumetric relaxation increased from 228±28msto 286±39 MS (n = 11; p0.001), starting from a somewhatlower value than P before withdrawal, reaching an insignificantlyhigher level and returning to the levels of P. During withdrawalof P stable values were encountered. Twelve weeks after withdrawal,there were no longer significant differences between M and Pgroups. In conclusion, after a one week gradual withdrawal ofM in patients with ischaemic heart disease, a transient increaseof both isovolumetric contraction and relaxation phases occur,suggesting depressed myocardial function, despite a transientrebound increase in heart rate.     

Repeated short periods of regional myocardial ischemia: effect on local function and high energy phosphate levels

Summary The effect of recurrent periods of ischemia on the myocardium was investigated in 15 open-chest dogs. Ischemia was produced by 3 minutes of proximal occlusion of the left anterior descending coronary artery. Each occlusion was followed by reperfusion of 3 minutes duration. Forty occlusions with a total of 120 minutes of ischemia were performed, and regional function (sonomicrometry) as well as high energy phosphates (needle biopsies) were determined at the end of the 5th, 20th, and 40th period of ischemia and reperfusion. The first periods of ischemia had a cumulative effect both on regional postischemic function (44% and 59% respectively of preischemic control after 20 occlusions) and on the ATP content, but with increasing number of occlusions the additive effects became smaller (ATP reduction/mol/gww/per occlusion). The ATP breakdown per occlusion was diminished with increasing number of periods of ischemia, and no significant adenosine was measured in the ischemic myocardium. Higher than normal postischemic creatine phosphate levels (9.1 mol/g w w at the 40th reperfusion vs. 6.7 mol/gw w control) indicated a functioning oxidative phosphorylation in the presence of an ATP utilization problem at the sarcomere level, because indicators of the cellular energy level (energy charge, free energy change of ATP hydrolysis) quickly normalized during reperfusion. Stunned myocardium is therefore not a problem of energy supply but rather of energy utilization. Reduced ATP utilization and regional dysfunction are the expressions of the same cellular defect which resides either in the ATP-splitting contractile apparatus or in the electromechanical coupling. Contractile dysfunction during reperfusion protects the heart against subsequent periods of ischemia because ATP turnover is reduced.Parts of the results were presented at the 57th Sessions of the American Heart Association, Miami, Florida/U.S.A. 1984     

Left ventricular function before and after kidney transplantation. A prospective study in patients with juvenile-onset diabetes mellitus

The aim of the present investigation was to discover whetherdisturbed left ventricular (LV) function limits renal replacementtherapy in patients with juvenile onset diabetes mellitus. Seventeenpatients given functioning kidney grafts were studied non-invasively(M-mode echocardiography, apexcardiography, phonocardiography)before renal transplant and an average of six, 13 and 44 monthsafter transplant. The main pretransplant findings were pronouncedLV hypertrophy with impaired diastolic LV function (prolongedrelaxation time + signs of decreased LV distensibility) anda hyperdynamic circulation. Most of these abnormalities were significantly less severe aftersuccessful kidney transplantation. LV mass decreased by 37%44 months after transplant (p<0.01) and LV diastolic andsystolic volumes decreased with a subsequent increase in ejectionfraction from 0.65 to 0.78 (p<0.01). The LV distensibilityand filling pattern improved significantly while the prolongedrelaxation time was unchanged. These findings imply that pretransplant disturbances in LV functionare related more to factors such as hypertension, volume overloadand uraemia than to diabetes per se because no pronounced improvementin the metabolic disorder resulting from diabetes can be expected,even after the most successful transplant. Disturbed LV functionshould not, therefore, exclude uraemic diabetics from renalreplacement.     

The Hunger Games: Homeostatic State-Dependent Fluctuations in Disinhibition Measured with a Novel Gamified Test Battery

Food homeostatic states (hunger and satiety) influence the cognitive systems regulating impulsive responses, but the direction and specific mechanisms involved in this effect remain elusive. We examined how fasting, and satiety, affect cognitive mechanisms underpinning disinhibition using a novel framework and a gamified test-battery. Thirty-four participants completed the test-battery measuring three cognitive facets of disinhibition: attentional control, information gathering and monitoring of feedback, across two experimental sessions: one after overnight fasting and another after a standardised meal. Homeostatic state was assessed using subjective self-reports and biological markers (i.e., blood-derived liver-expressed antimicrobial protein 2 (LEAP-2), insulin and leptin). We found that participants who experienced greater subjective hunger during the satiety session were more impulsive in the information gathering task; results were not confounded by changes in mood or anxiety. Homeostatic state did not significantly influence disinhibition mechanisms linked to attentional control or feedback monitoring. However, we found a significant interaction between homeostatic state and LEAP-2 on attentional control, with higher LEAP-2 associated with faster reaction times in the fasted condition only. Our findings indicate lingering hunger after eating increases impulsive behaviour via reduced information gathering. These findings identify a novel mechanism that may underpin the tendency to overeat and/or engage in broader impulsive behaviours.     

Effects of Daily Matcha and Caffeine Intake on Mild Acute Psychological Stress-Related Cognitive Function in Middle-Aged and Older Adults: A Randomized Placebo-Controlled Study

Matcha, a type of green tea, has a higher amino acid content than other types of tea. We previously examined the ability of matcha to improve cognitive function in older adults and determined that continuous matcha intake improves attention and executive function. This study aimed to compare the effects of matcha and caffeine and clarify the differences between these effects. The study was registered at the University Hospital Medical Information Network (UMIN000036578). The effect of single and continuous intake was compared, and the usefulness of continuous intake was evaluated under the stress condition. The Uchida–Kraepelin test (UKT) was used to induce mild acute stress, and the Cognitrax was used to evaluate cognitive function. A single dose of caffeine improved attentional function during or after stress loading. The reduced reaction time in the Cognitrax, observed following a single dose of matcha, was likely due to caffeine. The matcha group showed an increase in the amount of work after continuous intake, whereas the caffeine group only showed an increase in the amount of work for the UKT after a single dose. Ingesting matcha with caffeine improves both attention and work performance when suffering from psychological stress compared with caffeine alone.     

孕期胆固醇和氧化固醇与子代认知发育

胆固醇是大脑发育的重要物质基础,胚胎和胎儿发育需要母体持续转运胆固醇,氧化固醇是胆固醇的代谢物,包括胆固醇合成途径中的前体物和分结代谢过程中产生的代谢产物,可能与大脑功能密切相关。人群研究发现,孕妇血清/浆胆固醇水平与子代多动症、孤独症谱系障碍发病风险有关,但尚需进一步确证。