Facilitatory effects of 1 Hz rTMS in motor cortex of patients affected by migraine with aura

We previously showed paradoxical facilitatory effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on striate and extrastriate cortex of patients suffering migraine with aura. In this study we evaluated the effects of 1 Hz rTMS on the excitability of inhibitory and facilitatory circuits of motor cortex to explore whether the abnormal pattern of excitability extends beyond the sensory cortex also involving motor areas in migraine with aura. Nine patients affected by migraine with aura and eight healthy controls entered into the study. The hot spot for activation of the right abductor pollicis brevis (APB) was checked by means of a figure-of-eight coil and motor threshold (MT) recorded on this point. Nine hundred magnetic stimuli at 1 Hz frequency and 90% MT intensity were delivered at the hot spot. Before and after rTMS, intracortical inhibitory and facilitatory circuit excitability was assessed by means of a paired pulse paradigm (conditioning stimulus 80% MT and test stimulus 120% MT) with two different interstimulus intervals: 2 ms (inhibitory) and 10 ms (facilitatory). Amplitude of the responses was expressed as the percentage of motor evoked potential (MEP) to test stimulus alone. Results showed that in basal condition migraineurs present significantly reduced levels of intracortical inhibition (ICI) compared to controls. More importantly, opposite results were obtained in migraineurs with respect to controls when 1 Hz rTMS was applied. Specifically, whereas intracortical facilitation (ICF) significantly decreased in controls, it significantly increased in migraineurs. ICI levels were not significantly affected by low-frequency stimulation. Our results showed that motor as well as sensory cortex of migraine patients present an abnormal modulation of cortical excitability, where a relevant role is likely played by the inefficiency of inhibitory circuits.     

Elevated haemoglobin levels in the motor cortex following 1 Hz transcranial magnetic stimulation: a preliminary study

One hertz transcranial magnetic stimulation (TMS) over the motor cortex has been reported to increase activity in the motor cortex contralateral to stimulation, as evidenced by the elevated motor evoked potential on the corresponding hand muscle. Little research, however, has assessed concomitant changes in the haemoglobin level in the unstimulated motor cortex. An aim of this study was to measure the change of oxy- and deoxy-haemoglobin levels in the left motor cortex after 20 min of 1 Hz TMS over the right motor cortex. Subjects carried out a finger to thumb tapping task sequentially with six blocks of ten cycles (30 s on and 60 s off). One block was performed before TMS and five after TMS. The results show that the level of oxyhaemoglobin in the unstimulated cortex increased after TMS over the contralateral hemisphere and that the increase lasted 40 min after 1 Hz stimulation. Deoxy-haemoglobin was slightly decreased during the first 15 min after stimulation. The results identify long term physiological changes resulting from 1 Hz stimulation and help to inform our understanding of interhemispheric interactions in TMS studies.     

Absence of postexercise and delayed facilitation of motor cortex excitability in restless legs syndrome: evidence of altered cortical plasticity?

STUDY OBJECTIVE: Restless legs syndrome (RLS) is a neurologic disorder with well-defined clinical and diagnostic criteria but the pathophysiology of which is unclear. Previous studies have suggested alterations in motor cortex function in RLS. We aimed to compare motor cortex plasticity in subjects with RLS versus healthy controls. DESIGN: Biphasic single-pulse transcranial magnetic stimulation (TMS) of the nondominant hemisphere was used to define motor evoked potential (MEP) amplitude, motor threshold, and silent period. Subjects also performed 3 blocks (30-s, 60-s, and 90-s duration) of a bimanual motor task (exercise condition). Amplitude of MEPs elicited immediately after each block, and then after a 15-minute rest period were compared with baseline. The time course of intracortical inhibition was also tested using paired-pulse TMS at 1- to 6-millisecond interstimulus intervals. SETTING: Clinical neurophysiology laboratory in a General Hospital. STUDY PARTICIPANTS: For the single-pulse TMS procedures, the RLS group included 11 patients affected by primary RLS and the control group included 11 age- and sex-matched normal subjects. For the paired-pulse TMS procedures, there were 9 patients and 6 controls. INTERVENTIONS: None. RESULTS: There were no group differences in motor threshold and MEP amplitudes, but the silent period was significantly shorter in subjects with RLS. Compared with baseline, control subjects had larger MEP amplitudes after 30 and 60 seconds of exercise and also after the rest period. In contrast, MEP amplitudes in patients with RLS were not significantly different from baseline after any of the exercise conditions or following the rest period. Patients with RLS also had decreased short-latency paired-pulse inhibition. CONCLUSIONS: Findings show abnormal motor cortex inhibition and cortical excitability differences in RLS. We suggest the possibility of alterations in movement-related cortical plasticity in RLS.     

Interaction of two “polarization” dominant foci in the motor cortex

The effect of sequential treatments (with intervals of 30–60 min) to weak anodic direct currents (0.5–3 μA) to the representation area of the fore- and hindlimbs of the motor cortex were studied in conscious, non-immobilized rabbits. This procedure created foci of excitation with the properties of dominants, i.e., distant stimuli (sound, light) produced responses corresponding to behavioral reactions (limb movement). During formation of the second dominant focus, linked inhibition of excitation foci was seen at different time points: there was long-term inhibition of the first dominant focus by the second, which was followed by reciprocal inhibition between the excitation foci, which resembled a mutual relationship. The interaction of the two “polarization” dominant foci, consisting of the transient dominance of one and then the other focus, persisted over a long time scale (more than 1 h) after the current inducing the foci was switched off. These results provide evidence of the redistribution of excitation within the motor apparatus during formation of dominant foci in the motor cortex. Translated from Zhurnal Vysshei Nervoi Deyatel'nosti imeni I. P. Pavlova, Vol. 48, No. 4, pp. 607–615, July–August, 1998.     

Is somatosensory excitability more affected by the perspective or modality content of motor imagery?

Beneficial effects of mental practice likely arise because motor imagery involves largely similar neural networks as physical execution of the same movement. While it is known that the involvement of the motor system is favoured by focusing on the kinaesthetic modality and by the first person perspective, little is known about the impact of these factors on the somatosensory system. The present paper examines the effects on the somatosensory excitability of both perspective (the point of view of the person imagining a motor act) and modality (visual versus kinaesthetic) during mental practice. Seventeen healthy subjects participated. Quality of mental practice was controlled using chronometric tests and a subjective questionnaire. Excitability of the somatosensory system was assessed through the steady-state electroencephalographical response to a continuous train of electrical stimuli applied to the radial nerve, at the same time subjects were instructed to perform one of five tasks designed to separate the effects of perspective, modality and motor versus non-motor imagery. Kinaesthetic motor imagery exerts the largest effect on somatosensory excitability whereas visual motor imageries (1st and 3rd person perspectives) produce the same lower effect that static visual imagery does. Strikingly, specific effect of kinaesthetic motor imagery correlates with the selfselected speed to imagine and execute the same movement. These findings suggest a key role of the kinaesthetic content of motor imagery in recruiting the sensorimotor system.     

Activation of α1 and α2 noradrenergic receptors exert opposing effects on excitability of main olfactory bulb granule cells

The mammalian main olfactory bulb (MOB) receives a dense noradrenergic innervation from the pontine nucleus locus coeruleus that is important for neonatal odor preference learning and odor processing in mature animals. Modulation of GABAergic granule cells (GCs) is thought to play a key role in the net functional impact of norepinephrine (NE) release in the MOB, yet there are few direct studies of the influence of NE on these cells. In the present study we investigated noradrenergic modulation of GC excitability using electrophysiological approaches in rat MOB slices. A moderate concentration of NE (10 μM) and the α1 receptor agonist phenylephrine (10 μM) depolarized and increased spontaneous or current injection-evoked spiking in GCs. By contrast, low NE concentrations (0.1–1.0 μM) or the α2 receptor agonist clonidine (Clon, 10 μM) hyperpolarized and decreased the discharge of GCs. The effects of NE (10 μM) were blocked by antagonism of α1 and α2 receptors. Inhibitory effects of low NE concentrations were blocked or converted to excitatory responses by α2 receptor blockade, whereas excitatory effects of the moderate NE concentration were converted to inhibitory responses after α1 receptor blockade. NE (10 μM) and phenylephrine elicited inward currents that reversed near the potassium equilibrium potential. The effects of NE and phenylephrine were associated with increased membrane input resistance. Clonidine elicited an outward current associated with decreased membrane input resistance that reversed near the potassium equilibrium potential. These results indicate that α1 and α2 receptor activation exert opposing effects on GC excitability. Low concentrations of NE acting via α2 receptors suppress GC excitability, while higher concentrations of NE acting at α1 receptors increase GC excitability. These findings are consistent with recent findings that α1 and α2 receptor activation increase and decrease, respectively, GABAergic inhibition of mitral cells. The differential affinities of α1 and α2 noradrenergic receptor subtypes may allow for differential modulation of GABA release and olfactory processing as a function of the level of NE release, which in turn, is regulated by behavioral state.     

The amplitude and phase precision of 40 Hz auditory steady-state response depend on the level of arousal

The aim of this study was to investigate, in healthy subjects, the modulation of amplitude and phase precision of the auditory steady-state response (ASSR) to 40 Hz stimulation in two resting conditions varying in the level of arousal. Previously, ASSR measures have shown to be affected by the level of arousal, but the findings are somewhat controversial. Generally, ASSR is diminished in sleep but it may be increased in drowsiness. Besides, ASSR reduction has been observed in schizophrenia. However, schizophrenic patients are known to have a disturbance of arousal level, what makes it pertinent to know the effects of fluctuations in arousal on passive response to gamma-range stimulation. In nine healthy volunteers trains of 40 Hz click stimuli were applied during two conditions: in the “high arousal” condition subjects were sitting upright silently reading a book of interest; in the “low arousal” condition subjects were sitting in a reclined position with eyes closed and the lights turned off. The 64-channel EEG data was wavelet transformed and the amplitude and phase precision of the wavelet transformed evoked potential were decomposed by the recently proposed multi-subject non-negative multi-way factorization (NMWF) (Morup et al. in J Neurosci Methods 161:361–368, 2007). The estimates of these measures were subjected to statistical analysis. The amplitude and phase precision of the ASSR were significantly larger during the low arousal state compared to the high arousal condition. The modulation of ASSR amplitude and phase precision by differences in the arousal level during recording warrants caution when investigating oscillatory brain activity and interpreting the findings of reduced ASSR in schizophrenia. It also emphasizes the necessity of standardized recording procedures and monitoring the level of arousal during ASSR testing.     

Comparison of real beat-to-beat signals with commercially available 4 Hz sampling on the evaluation of foetal heart rate variability

Evaluation of foetal heart rate (FHR) variability is an essential part of foetal monitoring, but a precise quantification of this parameter depends on the quality of the signal. In this study, we compared real FHR beat-to-beat signals with 4 Hz sampling provided by commercial foetal monitors on linear and nonlinear indices and analysed their clinical implications. Simultaneous acquisition of beat-to-beat signals and their 4 Hz sampling rate counterparts was performed using a scalp electrode, during the last hour of labour in 21 fetuses born with an umbilical artery blood (UAB) pH ≥ 7.20 and 6 born with an UAB pH < 7.20. For each case, the first and last 10 min segments were analysed, using time and frequency domain linear, and nonlinear FHR indices, namely mean FHR, low frequency, high frequency, approximate, sample and multiscale entropy. Significant differences in variability indices were found between beat-to-beat and 4 Hz sampled signals, with a lesser effect seen with 2 Hz sampling. These differences did not affect physiological changes observed during labour progression, such as decreased entropy and linear time domain indices, and increased frequency domain indices. However, significant differences were found in the discrimination between fetuses born with different UAB pHs, with beat-to-beat sampling providing better results in linear indices and 4 Hz sampling better results in entropy indices. In conclusion, different FHR sampling frequencies can significantly affect the quantification of variability indices. This needs to be taken into account in the interpretation of FHR variability and in the development of new equipment.     

Complex spike activity in the oculomotor vermis of the cerebellum: a vectorial error signal for saccade motor learning?

Brain stem signals that generate saccadic eye movements originate in the superior colliculus. They reach the pontine burst generator for horizontal saccades via short-latency pathways and a longer pathway through the oculomotor vermis (OMV) of the cerebellum. Lesion studies implicate the OMV in the adaptation of saccade amplitude that occurs when saccades become inaccurate because of extraocular muscle weakness or behavioral manipulations. We studied the nature of the possible error signal that might drive adaptation by examining the complex spike (CS) activity of vermis Purkinje (P-) cells in monkeys. We produced a saccade error by displacing the target as a saccade was made toward it; a corrective saccade 200 ms later eliminated the resulting error. In most P-cells, the probability of CS firing changed, but only in the error interval between the primary and corrective saccade. For most P-cells, CSs occurred in a tight cluster 100 ms after error onset. The probability of CS occurrence depended on both error direction and size. Across our sample, all error directions were represented; most had a horizontal component. In more than one half of our P-cells, the probability of CS occurrence was greatest for error sizes <5° and less for larger errors. In the remaining cells, there was a uniform increased probability of CS occurrence for all errors 7–9°. CS responses disappeared when the target was extinguished during a saccade. We discuss the properties of this putative CS error signal in the context of the characteristics of saccade adaptation produced by the target displacement paradigm.     

Further studies on the antinociceptive effects ofΔ acid

The antinociceptive effects of (THC-7-oic) acid have been investigated further with particular regard to the influence of certain experimental parameters in the hot plate test. These included the degree of the thermal stimulus, the nature of the vehicle and a possible role for copper in the response. A temperature effect similar to that seen with nonsteroidalantiinflammatory drugs (NSAIDs) was observed, 55° produced observable antinociception, however, at a surface temperature of 58°C no drug effect was seen. Non-aqeous vehicles such as peanut oil increased the potency of THC-7-oic acid. Finally, the substitution of purified water for tap water reduced,the drug response which could be partially restored by adding copper to the purified drinking water. An increase in the inhibitory effect when copper was added was also seenin vitro in a cell culture model where the acid reduced prostaglandin synthesis induced by THC. Our findings suggest that THC-7-oic acid probably acts by mechanisms similar to the NSAIDs and that the above mentioned experimental conditions can greatly influence the outcome of studies with this agent.     

An iontophoretic study of the effects of α-amino-hydroxy-5-methyl-4-isoxazole propionic acid lesions of the nucleus basalis magnocellularis on cholinergic and GABAergic influences on frontal cortex neurones of rats

Unilateral lesions of the nucleus basalis magnocellularis (NBM) produced by -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid in rats caused, 8–10 weeks after the lesion, a 94% reduction in cortical acetylcholinesterase fibres and reduced activities of acetylcholinesterase and choline acetyltransferase by 70–80% in the frontal cortex ipsilateral to the lesion. In anaesthetized unlesioned control rats, iontophoretic administration of acetylcholine and carbachol produced atropine-sensitive inhibition and excitation of frontal cortical neurones, effects similar to those produced by electrically stimulating the NBM. The lesion reduced cortical neuronal firing rates but increased the percentage and sensitivity of neurones responding to acetylcholine, the predominant response changing from inhibition to excitation; response duration increased but latency was unaffected. The size of the response of individual neurones to carbachol, but not the percentage of sensitive neurones, was also increased in lesioned animals. The proportion of neurones responding to bicuculline and their individual sensitivities were increased by the lesion, suggesting that the lesion increased GABAergic tone; responses to glutamate were unchanged. The lesion did not affect the proportion of neurones in which acetylcholine modulated neuronal responses but reversed the nature of the modulation to predominantly excitatory; excitation was the predominant response to electrical forepaw stimulation in unlesioned control animals. This suggests a possible interaction between GABAergic and cholinergic mechanisms in selective attention and processing of cognitive information. Acute administration of di-isopropyl fluorophosphate to unlesioned animals significantly increased the number of frontal cortical neurones responding to acetylcholine, without affecting individual neuronal sensitivity or responses to carbachol and glutamate. The similarity of these effects to those of acetylcholine in lesioned animals suggests that the increased sensitivity to acetylcholine in the latter was due to loss of acetylcholinesterase, enabling diffusion of acetylcholine to more distant neurones. However, acetylcholinesterase does not hydrolyse carbachol and therefore it is necessary to postulate a different post-synaptic mechanism to explain the lesion-induced increases in the sensitivities of individual neurones to carbachol and to acetylcholine; interpretation of experimental findings should take these two mechanisms into account.     

Molecular mechanisms of the biphasic effects of interferon-γ on osteoclastogenesis

Although interferon-γ (IFN-γ) potently inhibits osteoclastogenesis, the suppressive effect is significantly reduced when osteoclast precursors are pre-exposed to the receptor activator of NF-κB (RANK) ligand (RANKL). However, the molecular mechanism underlying the biphasic effects of IFN-γ on osteoclastogenesis remains elusive. Here, we recapitulate the biphasic functions of IFN-γ in osteoclastogenesis in both tissue culture dishes and on bone slices. We further demonstrate that IFN-γ markedly suppresses the RANKL-induced expression of nuclear factor of activated T-cells c1 (NFATc1) in normal, but not RANKL-pretreated bone marrow macrophages (BMMs). Similarly, IFN-γ impairs the activation of the nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathways in normal, but not RANKL-pretreated, BMMs. These findings indicate that IFN-γ inhibits osteoclastogenesis partially by suppressing the expression of NFATc1 and the activation of the NF-κB and JNK pathways. Moreover, IFN-γ inhibits the RANKL-induced expression of osteoclast genes, but RANKL pretreatment reprograms osteoclast genes into a state in which they can no longer be suppressed by IFN-γ, indicating that IFN-γ inhibits osteoclastogenesis by blocking the expression of osteoclast genes. Finally, the IVVY(535-538) motif in the cytoplasmic domain of RANK is responsible for rendering BMMs refractory to the inhibitory effect of IFN-γ. Taken together, these findings provide important mechanistic insights into the biphasic effects of IFN-γ on osteoclastogenesis.     

The effects of 24 weeks of moderate- or high-intensity exercise on insulin resistance

This study was designed to investigate the effect of exercise intensity on insulin resistance by comparing moderate- and high-intensity interventions of equal energy cost. Maximum oxygen consumption (VO_2max), insulin, glucose and triglycerides were measured in 64 sedentary men before random allocation to a non-exercise control group, a moderate-intensity exercise group (three 400-kcal sessions per week at 60% of VO_2max) or a high-intensity exercise group (three 400-kcal sessions per week at 80% of VO_2max). An insulin sensitivity score was derived from fasting concentrations of insulin and triglycerides, and insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). Data were available for 36 men who finished the study. After 24 weeks, insulin concentration decreased by 2.54±4.09 and 2.37±3.35 mU l⁻¹, insulin sensitivity score increased by 0.91±1.52 and 0.79±1.37, and HOMA-IR decreased by −0.6±0.8 and −0.5±0.8 in the moderate- and high-intensity exercise groups, respectively. When data from the exercise groups were combined, one-way analysis of variance with one-tailed post hoc comparisons indicated that these changes were significantly greater than those observed in the control group (all P<0.05). Twenty-four week changes in insulin concentration, insulin sensitivity score and HOMA-IR were not significantly different between the exercise groups. These data suggest that exercise training is accompanied by a significant reduction in insulin resistance, as indicated by well-validated surrogate measures. These data also suggest that moderate-intensity exercise is as effective as high-intensity exercise when 400 kcal are expended per session.     

Modulatory Influence of Rarely Repeated Immobilization Episodes on the Interleukin-1β-Dependent Reaction of Blood Leukocytes and Hepatoprotective Effect of Restraint Stress

Repeated episodes of 1-h restraint stress were accompanied by a decrease in the sensitivity of blood leukocytes and cytochrome P450-dependent monooxygenases of the liver to recombinant IL-1β. These changes are associated with the anti-infl ammatory hepatoprotective effect of chronic stress.     

Regional characteristics of electrical responses (in the band 1–225 Hz) in the cerebral cortex to conditioned stimuli in operant conditioning

Power spectra of short-term (less than 1 sec) electrical responses to conditioned stimuli were studied over the frequency range 1–225 Hz in dogs during food-related operant conditioning. These spectra demonstrated regional characteristics in terms of energy levels and frequency composition. Responses were more marked in the visual and parietal areas of the left hemisphere. Power in responses to a differential stimulus were significantly lower than with responses to positive stimuli, mainly because of the high-frequency range (80–225 Hz); energy levels in these two situations were similar during prestimulus intervals. The frequency composition of responses was defined by a series of discrete frequencies in the gamma (30–80 Hz) and high-frequency ranges. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 55, No. 5, pp. 658–670, September–October, 2005.     

Tool perception suppresses 10-12Hz μ rhythm of EEG over the somatosensory area

The perception of tools vs. other objects has been shown to activate the premotor (BA6) and somatosensory cortex (BA3), which neurally represent object affordance related to tool manipulability (Proverbio et al., 2011). The earliest tool/non-tool discrimination is represented by increased anterior negativity (210-270ms) in response to tools. In this study, we analyzed μ desynchronization with wavelet analysis based on EEG recordings in response to 300 familiar objects vs. tools in 11 participants. The results showed an early 140-175ms μ desynchronization over centro-parietal sites at approximately 10-12Hz during tool perception. The surface scalp distribution of μ power is compatible with neural generators located in the somatosensory cortex, but no source analysis was performed. These results support the hypothesis that there is a temporal and functional relationship between the rapid and transient μ suppression over the centro/parietal area and the successive increase in time-locked post-synaptic potentials (ERPs) in regions processing tool motor affordance.     

The effects of APOE-ε4 on the BOLD response

In the last decade, functional magnetic resonance imaging (fMRI) has emerged as a tool to study changes in brain function associated with a genetic risk for Alzheimer's disease (AD), with a particular focus on the effects of the APOE-ε4 allele. This review compiles the existing literature concerning the effects of APOE genotype on the blood oxygen level dependent (BOLD) response, measured during task-based functional magnetic resonance imaging. While most studies report a significant difference in brain activity between carriers and noncarriers of the ε4 allele, there are inconsistencies in the direction and location of change. These inconsistencies were addressed by examining the effect of task, family history of Alzheimer's disease, and age on the relationship between APOE genotype and the BOLD response, but no clear pattern emerged. The review discusses the interpretation of BOLD differences between ε4 carriers and noncarriers, provides suggestions for future studies, and highlights important limitations of this type of research.     

Do the effects of job stressors on health persist over time? A longitudinal study with observational stressor measures

Observational work analyses were conducted among 222 office workers (131 women, 91 men) from 12 German companies to measure stressors independently of worker appraisal. Stressors were determined twice (1990, 1991), along with 7 health indicators separately assessed by questionnaire. Health indicators were assessed again in 1992 and once more in 1998. This 2-wave, 2-variable design with 2 follow-up measurements of health indicators determines (a) the causal directions using cross-lagged partial correlations (stressors seem to have an impact on health); (b) the strength of the impact (cross-lagged correlations for Waves 1 to 4 range from .18相似文献