Mika Kallio

Physiological Background of the Loss of Fractal Heart Rate Dynamics

Background—Altered fractal heart rate (HR) dynamics occur during various disease states, but the physiological background of abnormal fractal HR behavior is not well known. We tested the hypothesis that the fractal organization of human HR dynamics is determined by the balance between sympathetic and vagal outflow. Methods and Results—A short-term fractal scaling exponent (&agr;1) of HR dynamics, analyzed by the detrended fluctuation analysis (DFA) method, and the high-frequency (HF) and low-frequency (LF) spectral components of R-R intervals (0.15 to 0.4 Hz; n=13), along with muscle sympathetic nervous activity (MSNA) from the peroneus nerve (n=11), were assessed at rest and during cold face and cold hand immersion in healthy subjects. During cold face immersion, HF power increased (from 6.9±1.3 to 7.6±1.2 ln ms2, P<0.01), as did MSNA (from 32±17 to 44±14 bursts/100 heartbeats, P<0.001), and LF/HF ratio decreased (P<0.01). Cold hand immersion resulted in a similar increase in MSNA (from 34±17 to 52±19 bursts/100 heartbeats, P<0.001) but a decrease in HF spectral power (from 7.0±1.3 to 6.5±1.1 ln ms2, P<0.05) and an increase in the LF/HF ratio (P<0.05). The fractal scaling index &agr;1 decreased in all subjects (from 0.85±0.27 to 0.67±0.30, P<0.0001) during cold face immersion but increased during cold hand immersion (from 0.77±0.22 to 0.97±0.20, P<0.01). Conclusions—The fractal organization of human HR dynamics is determined by a delicate interplay between sympathetic and vagal outflow, with the breakdown of fractal HR behavior toward more random dynamics occurring during coactivation of sympathetic and vagal outflow.

Cardiovascular reflex testing contributes to clinical evaluation and differential diagnosis of Parkinsonian syndromes

The differentiation between Parkinsons disease (PD), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA) may be difficult but is important for prognostic and therapeutic purposes. Varying degrees of autonomic failure have been described in PD and MSA, whereas its involvement in PSP remains controversial. The aim of this study was to investigate autonomic function in patients fulfilling strict clinical diagnostic criteria for the disorders above, to evaluate the diagnostic capacity of laboratory autonomic tests. The study group was consecutively recruited among patients referred to a movement disorder unit. Thirty‐four patients with PD, 15 patients with PSP, and 47 patients with MSA were compared with 18 healthy age‐matched controls. Autonomic tests included analysis of heart rate variability (HRV) in temporal domain, at rest and during forced respiration, as well as blood pressure (BP) changes during 75° head‐up tilt.

Muscle-Derived Collagen XIII Regulates Maturation of the Skeletal Neuromuscular Junction

Formation, maturation, stabilization, and functional efficacy of the neuromuscular junction (NMJ) are orchestrated by transsynaptic and autocrine signals embedded within the synaptic cleft. Here, we demonstrate that collagen XIII, a nonfibrillar transmembrane collagen, is another such signal. We show that collagen XIII is expressed by muscle and its ectodomain can be proteolytically shed into the extracellular matrix. The collagen XIII protein was found present in the postsynaptic membrane and synaptic basement membrane. To identify a role for collagen XIII at the NMJ, mice were generated lacking this collagen. Morphological and ultrastructural analysis of the NMJ revealed incomplete adhesion of presynaptic and postsynaptic specializations in collagen XIII-deficient mice of both genders. Strikingly, Schwann cells erroneously enwrapped nerve terminals and invaginated into the synaptic cleft, resulting in a decreased contact surface for neurotransmission. Consistent with morphological findings, electrophysiological studies indicated both postsynaptic and presynaptic defects in Col13a1−/− mice, such as decreased amplitude of postsynaptic potentials, diminished probabilities of spontaneous release and reduced readily releasable neurotransmitter pool. To identify the role of collagen XIII at the NMJ, shed ectodomain of collagen XIII was applied to cultured myotubes, and it was found to advance acetylcholine receptor (AChR) cluster maturation. Together with the delay in AChR cluster development observed in collagen XIII-deficient mutants in vivo, these results suggest that collagen XIII plays an autocrine role in postsynaptic maturation of the NMJ. Altogether, the results presented here reveal that collagen XIII is a novel muscle-derived cue necessary for the maturation and function of the vertebrate NMJ.

Lack of Collagen XV Impairs Peripheral Nerve Maturation and, When Combined with Laminin-411 Deficiency, Leads to Basement Membrane Abnormalities and Sensorimotor Dysfunction

Although the Schwann cell basement membrane (BM) is required for normal Schwann cell terminal differentiation, the role of BM-associated collagens in peripheral nerve maturation is poorly understood. Collagen XV is a BM zone component strongly expressed in peripheral nerves, and we show that its absence in mice leads to loosely packed axons in C-fibers and polyaxonal myelination. The simultaneous lack of collagen XV and another peripheral nerve component affecting myelination, laminin α4, leads to severely impaired radial sorting and myelination, and the maturation of the nerve is permanently compromised, contrasting with the slow repair observed in Lama4−/− single knock-out mice. Moreover, the Col15a1−/−;Lama4−/− double knock-out (DKO) mice initially lack C-fibers and, even over 1 year of age have only a few, abnormal C-fibers. The Lama4−/− knock-out results in motor and tactile sensory impairment, which is exacerbated by a simultaneous Col15a1−/− knock-out, whereas sensitivity to heat-induced pain is increased in the DKO mice. Lack of collagen XV results in slower sensory nerve conduction, whereas the Lama4−/− and DKO mice exhibit increased sensory nerve action potentials and decreased compound muscle action potentials; x-ray diffraction revealed less mature myelin in the sciatic nerves of the latter than in controls. Ultrastructural analyses revealed changes in the Schwann cell BM in all three mutants, ranging from severe (DKO) to nearly normal (Col15a1−/−). Collagen XV thus contributes to peripheral nerve maturation and C-fiber formation, and its simultaneous deletion from neural BM zones with laminin α4 leads to a DKO phenotype distinct from those of both single knock-outs.

Sympatho‐vagal interaction in the recovery phase of exercise

Reciprocal autonomic regulation occurs during incremental exercise. We hypothesized that sympatho‐vagal interplay may become altered after exercise because of the differences in recovery patterns of autonomic arms. The cardiac vagal activity was assessed by measurement of beat‐to‐beat R–R interval oscillations using a Poincaré plot method (SD1), and muscle sympathetic nervous activity (MSNA) was measured from peroneus nerve by a microneurography technique during and after exercise in 16 healthy subjects. Autonomic regulation was compared between the rest and after exercise (3·5 ± 1·0 min after exercise) at equal heart rates (HR). SD1 was at the equal level at the recovery phase (40 ± 21 ms) compared to the resting condition (38 ± 16 ms, P = ns) at comparable HR (57 ± 10 for both). MSNA was higher at the recovery phase (40 ± 19 burst per 100 heartbeats) than at rest (25 ± 13 burst per 100 heartbeats, P<0·0001). The difference of MSNA activity between rest and late recovery phase had a strong positive correlation with the difference in SD1 (r = 0·78, P<0·001) at equal HRs. Subjects who have a higher sympathetic activity in the recovery phase of exercise have a more augmented cardiac vagal activity resulting in an accentuated sympatho‐vagal outflow. The altered autonomic interaction observed here may partly explain the clustering of various cardiovascular events to the recovery phase of exercise.

Autonomic Cardiac Regulation During Spontaneous Nocturnal Hypoglycemia in Patients With Type 1 Diabetes

OBJECTIVE Experimental clamp studies have suggested that hypoglycemia evokes a reduction of cardiac vagal control in patients with type 1 diabetes. However, there are limited data on the influence of spontaneous nocturnal hypoglycemia on cardiac autonomic regulation. RESEARCH DESIGN AND METHODS Adults with type 1 diabetes (n = 37) underwent continuous glucose monitoring via a subcutaneous sensor as well as recording of R-R interval or electrocardiogram for 3 nights. Heart rate (HR) variability was analyzed during periods of hypoglycemia (glucose <3.5 mmol/L) (minimum length of 20 min) and a control nonhypoglycemic period (glucose >3.9 mmol/L) of equal duration and at the same time of night. RESULTS The duration of hypoglycemic and control episodes (n = 18) ranged from 20 to 190 min (mean 71 min). HR (62 ± 7 vs. 63 ± 9 beats per min; P = 0.30) or the high-frequency component of HR power spectrum (2,002 ± 1,965 vs. 1,336 ± 1,506 ms2; P = 0.26) did not change during hypoglycemia. Hypoglycemia resulted in a significant decrease in the low-frequency component of HR variability (2,134 ± 1,635 vs. 1,169 ± 1,029 ms2, respectively; P = 0.006). The decline in the glucose concentration displayed a significant positive correlation with the decrease of the low-frequency component of HR variability (r = 0.48; P = 0.04). The latter was closely related to an increase in muscle sympathetic nerve activity recorded in 10 subjects during controlled sympathetic activation. CONCLUSIONS Spontaneous nocturnal hypoglycemia in patients with type 1 diabetes results in a reduction of the low-frequency component of HR, which is best explained by excessive sympathetic activation without a concomitant withdrawal of vagal outflow.

Physical Activity and Aerobic Fitness are Positively Associated With Heart Rate Variability in Obese Adults

BACKGROUND Autonomic nervous system (ANS) dysfunction and obesity are intrinsically related to each other. In normal-weight subjects physical activity (PA) and fitness are related to cardiovascular autonomic regulation, providing evidence that aerobic training may improve ANS functioning measured by heart rate variability (HRV). The goal of this study was to investigate the association between lifetime PA, aerobic fitness and HRV in obese adults. METHODS Participants included 107 (87 females) volunteers (mean age 44.5 years, median BMI 35.7) who completed health and lifestyle questionnaires and measurements of maximal aerobic performance, anthropometry and 24 h HRV. RESULTS In the multivariate linear regression analyses, lifetime physical activity explained 40% of the variance in normal R-R intervals (SDNN). Each 1-category increase in the activity index increased SDNN by 15.4 (P = .009) and 24% of the variance in natural logarithmic value of ultra-low frequency power (P = .050). High measured VO2max explained 45% of the variance in natural logarithmic value of high-frequency power (P = .009) and 25% of the variance in low frequency/high frequency ratio (P < .001). CONCLUSIONS Lifetime physical activity and aerobic fitness may reduce obesity-related health risks by improving the cardiac autonomic function measured by HRV in obese working-age subjects. This research supports the role of lifetime physical activity in weight management strategies and interventions to reduce obesity-related health risks.

Delayed N2 response in Go condition in a visual Go/Nogo ERP study in children who stutter

PURPOSE OF THE STUDY The main aim of the study was to investigate the attentional and inhibitory abilities and their underlying processes of children who stutter by using behavioural measurement and event-related potentials (ERP) in a visual Go/Nogo paradigm. METHODS Participants were 11 children who stutter (CWS; mean age 8.1, age range 6.3-9.5 years) and 19 typically developed children (TDC; mean age 8.1, age range 5.8-9.6 years). They performed a visual Go/Nogo task with simultaneous EEG recording to obtain ERP responses. RESULTS Results showed that CWS had longer N2 and P3 latencies in the Go condition compared to the TDC. In contrast, the groups did not differ significantly in the Nogo condition or behavioural measures. CONCLUSIONS Our findings did not confirm less efficient inhibitory control in CWS but suggest atypical attentional processing such as stimulus evaluation and response selection. EDUCATIONAL OBJECTIVES The reader will be able to (a) describe recent findings on attention and inhibitory control in children who stutter, (b) describe the measurement of attentional processing, including inhibitory control, and (c) describe the findings on attentional processing in children who stutter as indexed by the event-related potentials in a visual Go/Nogo paradigm.

Atypical brain activation in children who stutter in a visual Go/Nogo task: An ERP study

OBJECTIVE The aim of the study was to investigate inhibitory control by evaluating possible differences in the strength and distribution of the brain activity in a visual Go/Nogo task in children who stutter (CWS) compared to typically developing children (TDC). METHODS Eleven CWS and 19 TDC participated. Event related potentials (ERP) were recorded using a 64-channel EEG-cap during an equiprobable visual Go/Nogo task. The global field power (GFP) as well as the mean amplitudes in the P3 time frame were compared between groups. Additionally, the potential maps of the groups were investigated visually in the N2 and P3 time windows. RESULTS The groups differed significantly in the right frontal area especially in the Nogo condition (p<0.001) with CWS showing smaller (less positive) mean amplitudes, most likely due to a prolonged and asymmetrical N2 component. Also the fronto-central Nogo P3 component was rather indistinct in CWS, but easily recognizable in TDC in the potential maps. CONCLUSIONS The CWS show atypical brain activation compared to the TDC in a Go/Nogo task as indexed by the excessive N2-related activity in both conditions and reduced P3-related activity in Nogo condition. SIGNIFICANCE These findings indicate atypical stimulus evaluation and response inhibition processes in CWS.

Exercise and Fitness Are Related to Peripheral Nervous System Function in Overweight Adults

PURPOSE This study examined the association between physical activity and fitness and peripheral nervous system (PNS) function in overweight and obese individuals. METHODS Forty nondiabetic overweight adults (mean +/- SD; age = 44 +/- 11 yr) were recruited for the study. Peroneal motor nerve and radial, sural, and medial plantar sensory nerve conductions were studied. Maximal oxygen uptake was measured in an incremental bicycle ergometer test. Physical activity was assessed by accelerometer and self-reporting. We analyzed the data using multiple stepwise linear regression models adjusted for age, height, and skin temperature. RESULTS VO2max predicted 17% of peroneal distal compound muscle action potential (CMAP) amplitude variation and 16% of peroneal proximal CMAP amplitude variation. Physical activity index at the age of 30 yr predicted 9% of peroneal motor nerve conduction velocity (NCV), 8% of peroneal F-wave maximum latency, 14% of medial plantar sensory latency, and 10% of medial plantar sensory NCV variation. CONCLUSIONS Physical activity and fitness are positively associated with PNS function and should be encouraged in overweight people.