Neurophysiologic markers of primary motor cortex for laryngeal muscles and premotor cortex in caudal opercular part of inferior frontal gyrus investigated in motor speech disorder : a navigated transcranial magnetic stimulation (TMS) study

Transcranial magnetic stimulation studies have so far reported the results of mapping the primary motor cortex (M1) for hand and tongue muscles in stuttering disorder. This study was designed to evaluate the feasibility of repetitive navigated transcranial magnetic stimulation (rTMS) for locating the M1 for laryngeal muscle and premotor cortical area in the caudal opercular part of inferior frontal gyrus, corresponding to Broca's area in stuttering subjects by applying new methodology for mapping these motor speech areas. Sixteen stuttering and eleven control subjects underwent rTMS motor speech mapping using modified patterned rTMS. The subjects performed visual object naming task during rTMS applied to the (a) left M1 for laryngeal muscles for recording corticobulbar motor-evoked potentials (CoMEP) from cricothyroid muscle and (b) left premotor cortical area in the caudal opercular part of inferior frontal gyrus while recording long latency responses (LLR) from cricothyroid muscle. The latency of CoMEP in control subjects was 11.75 +/- A 2.07 ms and CoMEP amplitude was 294.47 +/- A 208.87 A mu V, and in stuttering subjects CoMEP latency was 12.13 +/- A 0.75 ms and 504.64 +/- A 487.93 A mu V CoMEP amplitude. The latency of LLR in control subjects was 52.8 +/- A 8.6 ms and 54.95 +/- A 4.86 in stuttering subjects. No significant differences were found in CoMEP latency, CoMEP amplitude, and LLR latency between stuttering and control-fluent speakers. These results indicate there are probably no differences in stuttering compared to controls in functional anatomy of the pathway used for transmission of information from premotor cortex to the M1 cortices for laryngeal muscle representation and from there via corticobulbar tract to laryngeal muscles.Peer reviewe

Neurophysiologic markers of primary motor cortex for laryngeal muscles and premotor cortex in caudal opercular part of inferior frontal gyrus investigated in motor speech disorder : a navigated transcranial magnetic stimulation (TMS) study

Transcranial magnetic stimulation studies have so far reported the results of mapping the primary motor cortex (M1) for hand and tongue muscles in stuttering disorder. This study was designed to evaluate the feasibility of repetitive navigated transcranial magnetic stimulation (rTMS) for locating the M1 for laryngeal muscle and premotor cortical area in the caudal opercular part of inferior frontal gyrus, corresponding to Broca's area in stuttering subjects by applying new methodology for mapping these motor speech areas. Sixteen stuttering and eleven control subjects underwent rTMS motor speech mapping using modified patterned rTMS. The subjects performed visual object naming task during rTMS applied to the (a) left M1 for laryngeal muscles for recording corticobulbar motor-evoked potentials (CoMEP) from cricothyroid muscle and (b) left premotor cortical area in the caudal opercular part of inferior frontal gyrus while recording long latency responses (LLR) from cricothyroid muscle. The latency of CoMEP in control subjects was 11.75 +/- A 2.07 ms and CoMEP amplitude was 294.47 +/- A 208.87 A mu V, and in stuttering subjects CoMEP latency was 12.13 +/- A 0.75 ms and 504.64 +/- A 487.93 A mu V CoMEP amplitude. The latency of LLR in control subjects was 52.8 +/- A 8.6 ms and 54.95 +/- A 4.86 in stuttering subjects. No significant differences were found in CoMEP latency, CoMEP amplitude, and LLR latency between stuttering and control-fluent speakers. These results indicate there are probably no differences in stuttering compared to controls in functional anatomy of the pathway used for transmission of information from premotor cortex to the M1 cortices for laryngeal muscle representation and from there via corticobulbar tract to laryngeal muscles.Peer reviewe

The Insulin-Mediated Modulation of Visually Evoked Magnetic Fields Is Reduced in Obese Subjects

BACKGROUND: Insulin is an anorexigenic hormone that contributes to the termination of food intake in the postprandial state. An alteration in insulin action in the brain, named "cerebral insulin resistance", is responsible for overeating and the development of obesity. METHODOLOGY/PRINCIPAL FINDINGS: To analyze the direct effect of insulin on food-related neuronal activity we tested 10 lean and 10 obese subjects. We conducted a magnetencephalography study during a visual working memory task in both the basal state and after applying insulin or placebo spray intranasally to bypass the blood brain barrier. Food and non-food pictures were presented and subjects had to determine whether or not two consecutive pictures belonged to the same category. Intranasal insulin displayed no effect on blood glucose, insulin or C-peptide concentrations in the periphery; however, it led to an increase in the components of evoked fields related to identification and categorization of pictures (at around 170 ms post stimuli in the visual ventral stream) in lean subjects when food pictures were presented. In contrast, insulin did not modulate food-related brain activity in obese subjects. CONCLUSIONS/SIGNIFICANCE: We demonstrated that intranasal insulin increases the cerebral processing of food pictures in lean whereas this was absent in obese subjects. This study further substantiates the presence of a "cerebral insulin resistance" in obese subjects and might be relevant in the pathogenesis of obesity

Serological Response to SARS-CoV-2 Vaccine in Hemodialyzed Patients and the Association with Later COVID-19 Positivity

Background: The effectiveness of the COVID-19 vaccine may differ in hemodialysis patients. The aim of this prospective multicenter study was to determine the degree of serological response to the SARS-CoV-2 vaccine in the population of dialysis patients and its association with later SARS-CoV-2 infections. Methods: A blood sample was taken for the determination of COVID-19 serological status (IgG antibodies) in 706 dialysis patients 16 weeks after vaccination with the second dose (Pfizer-BioNTech). Results: Only 314 (44.5%) hemodialyzed patients had a satisfactory response to the COVID-19 vaccine. Eighty-two patients (11.6%) had a borderline response, while 310 patients (43.9%) had an unsatisfactory (negative) post-vaccinal antibody titer. A longer dialysis vintage had an increased odds ratio (OR) of 1.01 for the occurrence of COVID-19 positivity after vaccination. In the group of subsequently positive patients, 28 patients (13.6%) died from complications of COVID-19. We have found differences in mean survival time between patients with and without appropriate responses to vaccination in favor of patients with a satisfactory serological response. Conclusions: The results showed that the dialysis population will not have the same serological response to the vaccine as the general population. The majority of dialysis patients did not develop a severe clinical picture or die at the time of positivity for COVID-19

Primer sequences used in RT-PCR analysis.

<p>Primer sequences used in RT-PCR analysis.</p

Bone biomarkers and hormones in high-5HT and low-5HT rats.

<p>Depicted are relative differences (%): for the overall difference between the high-5HT (H) and low-5HT (L) sublines, P<0.05 is considered significant; for contrasts between sublines at a given age and between different ages within the same subline, P<0.025 is considered significant (n = 5–10 rats/group). H-L indicates a difference between high-5HT and low-5HT animals. 12–2 indicates a difference between 12 months and 2 months old animals.</p

Systemic role of the peripheral 5HT.

<p>Gut synthesized 5HT enters the platelets via the 5HTT. The quantity of 5HT in platelets depends on the 5HTT activity, while the rate of 5HT synthesis in the gut is equal between both rat sublines (≈ sign). Changes in the serum Ca²⁺ level, influenced by PTH from parathyroid glands and by 1,25(OH)₂D₃ from the kidney, impact the platelet 5HTT activity, with a bidirectional effect on PSL (green-red arrow). Elevated 5HT bidirectionally influences the plasma insulin level (green-red arrow) and induces the hyperthrophy of pancreatic β-cells (dashed arrow), leading to type 2 diabetes with an increased plasma glucose, insulin resistance, glucose intolerance, visceral fat volume and decreased muscle strength. In return, plasma insulin level positively correlates with the PSL (+ sign). Increased insulin and 5HT have an additive effect on bone formation (green arrow). Elevated 5HT increases both bone formation and resorption (larger green arrow), thus increasing the bone turnover and resulting in the net bone loss (large red arrow). 5HT—serotonin, 5HTT—serotonin transporter, PSL—plasma serotonin level, PTH—parathyroid hormone.</p

Physiological characteristics of rats from high-serotonin (5HT) and low-5HT sublines.

<p>A. Indicators of 5HT homeostasis shown as “fold difference” between high- and low-5HT animals with 95% confidence intervals. Reference values were (mean±SD): a) for platelet serotonin level (PSL) 0.80±0.08 μg 5HT/mg platelet protein; b) for platelet serotonin uptake (PSU) 0.69±0.07 nmol 5HT/mg platelet protein/min. Rats were 2 months (PSU measurements) and 12 months (gut <i>Mao-A</i>, <i>Tph1</i> and <i>5HTT</i> expression) of age. PSL and gut 5HT turnover data are given for animals of 2 and 12 months of age. B. No difference in 5HT production and storage in the gut was observed between high- and low-5HT rat sublines. 5HT visualized by using immunohistochemistry was documented at 40× magnification and is depicted by black arrows. C-E. Physical characteristics of high-5HT and low-5HT animals (mean±SD). High-5HT animals are represented by black squares, low-5HT animals by open circles. C—body weight; D—femur length; E—hanging time in the string test (mean values from three 60-sec trials separated by 10-min intervals). Relative differences (%) are shown for subline*age interaction contrasts. P-values were adjusted for multiple comparisons (n = 6–15 rats/group). H-L indicates a difference between high-5HT and low-5HT animals. 12–2 indicates a difference between 12 months and 2 months old animals. Mao-A—monoamine oxidase A; Tph1 –tryptophan hydroxylase 1; 5HTT—serotonin transporter</p

3D model of trabecular bone reconstructed from μCT images for lumbar spine and distal femur in high-5HT and low-5HT rats at 2 and 12 months of age.

<p>A. Spine—μCT images. B-D. Spine—morphometric indices (mean±SD). E. Femur—μCT images. F-H. Femur—morphometric indices (mean±SD). Shown are relative differences (%): H-L (high-5HT vs. low-5HT animals) at different age; 12–2 months for high and low 5HT animals (n = 8–14 rats/group). Depicted are relative differences (%): for the overall difference between the high-5HT and low-5HT sublines, P<0.05 is considered significant; for contrasts between sublines at a given age and between different ages within the same subline, P<0.025 is considered significant.</p

<i>In vivo</i> effects of <i>Tph1</i> inhibition on platelet serotonin levels (PSL) and bone parameters in 12 months old high 5-HT subline.

<p>On day 1 of the experiment, PSL was measured and treatment with LX1032 (25 mg/kg) (n = 7) or vehicle (control, n = 6) was commenced. At the last day of treatment (Day 36), PSL was determined again. Animals were sacrificed 24 h after the last dose and bone volume (BV/TV, %), trabecular spacing (TbSp, mm) and number of trabecules (Tb.N, 1/mm) were determined in the femur and spine using μCT. A. Data are geometric means (±geometric SD) of PSL values on Day 1 and Day 36. A general linear mixed model (treatment, day [random], treatment*day interaction) was fitted to ln(PSL) and differences (expressed as percentages derived from geometric means ratios) were determined: a) in PSL between the two groups on days 1 and 36; b) in PSL between days 36 and 1, within each group; c) in change in PSL from Day 1 to Day 36 (interaction term coefficient) between the two groups. Adjustment for multiple comparisons was by the simulation method. B. Data are means (±SD) by bone parameter by group, separately for the femur and spine. A separate general linear model was fitted to each of the six ln-transformed outcomes. Differences between groups are expressed as percentage differences (derived from geometric means ratios). C. Non-parametric (Kendall's) regression of bone parameters on change in PSL from the start to the end of treatment. Data depict median slope with confidence interval, Kendall's tau coefficient and P-value.</p