The effect of transcranial magnetic stimulation and peripheral nerve stimulation on corticomuscular coherence in humans

Cortex and muscle show coupled oscillations in the 15–35 Hz frequency band during voluntary movements. To obtain evidence of the neuronal network responsible for this rhythmicity we investigated the effect of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation on the coupling between eletcroencephalographic (EEG) activity recorded from the scalp over the motor cortex and electromyographic (EMG) activity recorded from the tibialis anterior (TA) muscle in 15 healthy human subjects. TMS over the leg area at intensities between 0.95 and 1.1 × threshold for a motor evoked potential (MEP) in the TA increased corticomuscular coherence in the 15–35 Hz frequency band. This effect lasted on average for 300 ms, but could last up to 600–800 ms in some subjects. Stimulation of motor nerves from the ankle muscles suppressed corticomuscular coherence in the 15–35 Hz frequency range between leg area EEG and TA EMG for a period up to 600–800 ms. In addition, increased coherence around 10 Hz was observed for a period up to 250 ms after the stimulation. Stimulation of motor nerves in the arm and motor nerves from the ankle muscles in the other leg had no effect. The findings indicate that TMS has direct access to the neuronal circuitry in the motor cortex, which generates the corticomuscular coherence. This effect was caused either by direct activation of corticospinal cells or by activation of local neuronal circuitries in the motor cortex. The effects of peripheral nerve stimulation suggest that an alternative rhythm generator may entrain the cortical cells into a lower 10 Hz rhythm and disrupt the 15–35 Hz rhythm.     

Absence of gamma-range corticomuscular coherence during dynamic force in a deafferented patient

Recently, we studied corticomuscular coherence (CMC) in a visuomotor task and showed for the first time gamma-range (30–45 Hz) CMC during isometric compensation of a periodically modulated dynamic force. We speculated that for the control of such forces, the sensorimotor system resonates at gamma-range frequencies to rapidly integrate the visual and proprioceptive information and produce the appropriate motor command. In this study, we tested the role of the proprioceptive afferent feedback on gamma-range CMC by comparing the deafferented patient GL to six age- and sex-matched subjects during the performance of a visuomotor force task consisting of isometric compensation of static and dynamic forces applied on the finger. Patient GL presented no significant gamma-band CMC during dynamic force. Instead, she had only beta-range CMC as in the static force condition; concurrently, her performance was significantly worse than that of the controls in both conditions. This gives support to the conclusions of our previous paper and suggests that proprioceptive information is mandatory in the genesis of gamma-band CMC during the generation and control of dynamic forces.     

Modulation of spinal reflexes by aversive and sexually appetitive stimuli

In this study, modulation of spinal tendinous (T) reflexes by sexual stimulation was investigated. T reflexes are augmented in states of appetitive and defensive action and modified by differences in arousal intensity. Reflexes were expected to be facilitated by both pleasant (sexual) and unpleasant (anxiety) stimuli. Subjects were exposed to a sexual, an anxiety-inducing, a sexually threatening, and a neutral film excerpt. Genital arousal, emotional experience, subjective action tendencies, and T reflexes were monitored. Self-report and genital data confirmed the affective states as intended. T reflex amplitude significantly increased during viewing of emotionally arousing film excerpts as compared with a neutral film excerpt. T reflexes were facilitated by the sex stimulus to the same extent as by the anxiety and sexual threat stimuli. The results support the view of sexual arousal as an emotional state, generating sex-specific autonomic and general somatic motor system responses, which prepare the organism for action.     

Modulation of behavioral and insulin responses by contextual stimuli paired with food

A context-like conditioned stimulus (CS) previously paired with a food unconditioned stimulus (US) enhanced both food-related activity and insulin secretion in rats. Experiment 1 documented the effectiveness of an appetitive conditioning procedure in which a 10 sec visual CS ("x") was followed by food when embedded within one 35 sec auditory CS ("A"), but not another ("B"). Approach to a food magazine during x was enhanced (facilitated) when x was within A, as compared to within B or alone. Experiment 2 documented the adequacy of blood sampling and insulin assay procedures that could be accommodated to the conditioning procedure. Plasma insulin was observably different after unconditioned deliveries of glucose solutions of different intensities. In Experiment 3, training as in Experiment 1 was followed by testing for food magazine approach and changes in insulin levels following x alone or in the presence of A or B. It was demonstrated that the A cue enhanced both responses. The results support the view [e.g., (18,19)] that insulin secretion is in part under the control of environmental cues, and findings (22) that show that conditioned context-like cues can modulate consummatory responding to punctate CSs.     

Modulation of the soleus H reflex by electrical subcortical stimuli in humans

Over the past two decades, the H reflex has been used as a neural tool to assess the effect on the motoneuronal pool of conditioning volleys in supraspinal descending tracts elicited by transcranial magnetic stimulation (TMS) or auditory stimuli. However, mechanisms mediating such modulation are unclear. These hypothesized neural pathways are likely to be affected by single electrical stimulus applied through the electrodes implanted in the subthalamic nucleus for deep brain stimulation (sSTNDBS). To improve our knowledge on such mechanisms, we examined in 11 Parkinson’s disease patients the effects of conditioning sSTNDBS applied contralateral and ipsilateral to the H reflex recording on the amplitude of the soleus H reflex, at interstimulus intervals (ISIs) between 0 and 110 ms. There was a significant main effect of the ISI (P < 0.001) and of the sSTNDBS stimulation side (P = 0.019) on the percentage change in the soleus H-reflex amplitude. Contralateral sSTNDBS modulation of the soleus H reflex resembles that of TMS in healthy subjects with two facilitation phases (at 5–20 ms and at 60 ms), while after ipsilateral sSTNDBS, there is only a single facilitation phase peaking up at 5 ms later than the first facilitation period observed with contralateral stimulation. These findings contribute to the discussion of the mechanisms underlying the excitability of the spinal alpha motoneuron pool and the modulation of the H reflex by supraspinal stimuli.     

Modulation of peripheral inflammation by locally administered endomorphin-1

OBJECTIVES: Neurogenic inflammation is mediated via sensory peptides released from the peripheral terminals of sensory nerves and can be modulated by locally released opioid peptides at the site of injury. Endomorphins are recently discovered endogenous opioid peptides with high selectivity and affinity for the mu-opioid receptor. The aim of this study was to examine the ability of endomorphin-1 (EM-1) to modulate the inflammatory response under different injury conditions. METHODS: A vacuum-induced blister model in anaesthetised rats (nembutal 60 mg/kg i.p.) was used to examine the effect of EM-1 on the acute inflammatory response induced by; (1) electrical stimulation (ES) of the distal portion of the exposed/cut sciatic nerve at 20 V, 5 Hz, 2 ms for 1 min or; (2) superfusion of substance P (SP) over the blister base. In addition, the effect of EM-1 on the inflammatory response to SP was examined under acute, recurrent (repeated blister induction) and chronic (chronic sciatic nerve lesion) injury conditions. RESULTS: Prior and concomitant perfusion of EM-1 (100 microM) significantly inhibited the vascular response to ES by 58% compared to controls. EM-1 also inhibited the inflammatory response to SP (both vasodilatation and plasma extravasation) in a dose-dependent manner. Significant inhibition was achieved at 100 microM and 1 mM concentrations of EM-1. Naloxone (1 mg/kg i.v.) reversed the inhibitory effect of EM-1 on the inflammatory response to SP. EM-1 (100 microM) was equally potent in inhibiting the inflammatory response to SP under acute (34% inhibition) recurrent (39%) and chronic (42%) injury conditions. CONCLUSIONS: The current results demonstrate a greater inhibitory effect of EM-1 on the inflammatory response to electrical nerve stimulation (58% inhibition) compared to SP (34% inhibition) suggesting the involvement of both pre- and post-terminal mechanisms in the inhibitory modulatory actions of EM-1. Evidence is provided for the involvement of opioid receptors in this inhibitory effect. The results also suggest that EM-1 is equipotent in inhibiting the inflammatory response under different injury conditions.     

Modulation of the reaction of hippocampal neurons to sensory stimuli by cholinergic substances

The influences of increasing endogenous acetylcholine (eserine) and its blockade (scopolamine) on the effects of sensory stimuli were analyzed through the extracellular recording of the activity of individual hippocampal neurons of awake rabbits. An increase in the level of acetylcholine, accompanied by the appearance of stable theta rhythm, leads to a substantial decrease in the reactivity of neurons, the suppression, attenuation, and inversion of the majority of inhibitory reactions and of a substantial proportion of activational reactions including on-responses of a specific type. At the same time, a limited group of activational reactions is intensified and extended against the background of eserine. Scopolamine, which blocks theta rhythm, does not change or intensifies inhibitory and some activational reactions, including on-responses. Tonic reactions are shortened; however, their gradual extinction disappears. The effects described are preserved in the hippocampus in the presence of basal undercutting of the septum which eliminates ascending brainstem pathways. These data make it possible to draw the conclusion that, under normal conditions, a new (significant) sensory stimulus elicits in the hippocampus an initial stoppage (reset) of activity with the coordinated triggering of theta rhythm and the passage against this background of signals along the cortical input in a specific phase relationship to it. The period of theta modulation switched on by the signal fosters its recording and the limitation of the passage of subsequent, interfering signals. The septohippocampal influences may thus support the mechanism of selective attention, as a necessary precondition for memory. This study carried out with the financial support of the Russian Basic Research Fund (Project No. 93-04-21907). Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 45, No. 1, pp. 118–131, January–February, 1995.     

Between-subject variance in the magnitude of corticomuscular coherence during tonic isometric contraction of the tibialis anterior muscle in healthy young adults

Oscillatory activity of the sensorimotor cortex has been reported to show coherence with muscle activity in the 15- to 35-Hz frequency band (β-band) during weak to moderate intensity of isometric contraction. The present study examined the variance of the magnitude of the corticomuscular coherence across a large number of subjects. We quantified the coherence between EEG over the sensorimotor cortex and rectified electromyogram (EMG) from the tibialis anterior muscle during tonic isometric contraction at 30% of maximal effort in 100 healthy young individuals. We estimated the maximal peak of EEG-EMG coherence (Cohmax) and the ratio of the sum of the autopower spectral density function within the β-band to that of all frequency ranges for both EEG (EEGβ-PSD) and EMG (EMGβ-PSD) signals. The frequency histogram of Cohmax across all subjects showed a broad bell-shaped continuous distribution (range, 0.048-0.816). When the coherence was thresholded at the estimated significance level of P < 0.05 (0.114), 46 out of 100 subjects showed significant EEG-EMG coherence. Cohmax occurred within the β-band in the majority of subjects who showed significant EEG-EMG coherence (n = 43). Furthermore, Cohmax showed significant positive correlations with both EEGβ-PSD (r = 0.575, P < 0.001) and EMGβ-PSD (r = 0.606, P < 0.001). These data suggest that even during simple tonic isometric contraction, the strength of oscillatory coupling between the sensorimotor cortex and spinal motoneurons varies among individuals and is a contributory factor determining muscle activation patterns such as the degree of grouped discharge in muscle activity within the β-band for each subject.     

Modulation of human peripheral blood eosinophil function by tumor necrosis factor-alpha

Eosinophils are important effectors in helminthic parasitic infection. Tumor necrosis factor (TNF-alpha) has been implicated as a mediator in the host response to parasitic infection and enhances eosinophil-mediated helminthotoxicity. We have examined the direct effects of recombinant human (rh) TNF on eosinophil functions of degranulation and oxidative metabolism. This report describes the minimal effects of rhTNF-alpha on eosinophil superoxide anion generation and enzyme secretion, which do not satisfactorily explain the observed increases in helminthotoxicity. In contrast to other cell types, eosinophils are unique in their differential responses to interleukin-1 beta and TNF.     

Foveal attention modulates responses to peripheral stimuli

When attending to a visual object, peripheral stimuli must be monitored for appropriate redirection of attention and gaze. Earlier work has revealed precentral and posterior parietal activation when attention has been directed to peripheral vision. We wanted to find out whether similar cortical areas are active when stimuli are presented in nonattended regions of the visual field. The timing and distribution of neuromagnetic responses to a peripheral luminance stimulus were studied in human subjects with and without attention to fixation. Cortical current distribution was analyzed with a minimum L1-norm estimate. Attention enhanced responses 100-160 ms after the stimulus onset in the right precentral cortex, close to the known location of the right frontal eye field. In subjects whose right precentral region was not distinctly active before 160 ms, focused attention commonly enhanced right inferior parietal responses between 180 and 240 ms, whereas in the subjects with clear earlier precentral response no parietal enhancement was detected. In control studies both attended and nonattended stimuli in the peripheral visual field evoked the right precentral response, whereas during auditory attention the visual stimuli failed to evoke such response. These results show that during focused visual attention the right precentral cortex is sensitive to stimuli in all parts of the visual field. A rapid response suggests bypassing of elaborate analysis of stimulus features, possibly to encode target location for a saccade or redirection of attention. In addition, load for frontal and parietal nodi of the attentional network seem to vary between individuals.     

Modulation of nerve growth factor in peripheral organs by estrogen and progesterone

Nerve growth factor (NGF) synthesized in peripheral organs plays a critical role in the development and maintenance of the nervous system and also participates in processing nociceptive stimuli. Previous studies suggest that reproductive hormones may regulate the expression of NGF. Ovariectomies were performed on female mice, and mice were killed 24 h after hormone replacement to evaluate the effects of estrogen and progesterone on NGF in peripheral organs, specifically the uterus, bladder, heart, and salivary gland. Sham-operated intact mice and untreated ovariectomized mice served as controls. Immunohistochemistry demonstrated the presence of NGF, estrogen receptor-alpha, estrogen receptor-beta, and progesterone receptors in these organs. Ovariectomy caused a significant decrease in NGF protein content in the uterus, and short term treatment of ovariectomized mice with estrogen and/or progesterone increased uterine NGF mRNA and restored NGF protein to concentrations similar to intact control mice. Ovariectomy did not affect NGF protein concentrations in the salivary gland, but treatment of ovariectomized mice with estrogen alone or in conjunction with progesterone stimulated concentrations of NGF protein that exceeded those observed in intact control or ovariectomized, untreated mice. NGF mRNA was increased in salivary glands from ovariectomized mice treated with progesterone alone or in combination with estrogen relative to other groups. NGF protein content of the hearts of ovariectomized mice treated with estrogen alone or in conjunction with progesterone was increased relative to intact controls and ovariectomized, untreated mice, but neither ovariectomy or hormone replacement affected NGF mRNA content in the heart. NGF protein content of the bladder was unaffected by ovariectomy or hormone treatment, and bladder NGF mRNA was unaffected by ovariectomy or hormone treatment. Collectively, these results indicate that reproductive hormones have the capacity to regulate NGF message and protein in a manner that varies among organs. Fluctuations in the expression of NGF, in conjunction with other factors, may help to explain gender differences in pain sensation and inflammatory response.     

Body temperature cues as contextual stimuli: Modulation of hypothermia-induced retrograde amnesia

Three experiments investigated whether the retention of passive avoidance training after the induction of amnesia by hypothermia could be modulated by the presence or absence of cold body temperature cues. In Experiment 1A, the cues for recovery from amnesia produced by a recooling treatment were erased by a 5, 10, or 15 min, but not by a 1 min, immersion in normothermic water. Similarly, Experiment 1B noted the erasure of the recooling reactivation effect by a 10 or 20 min immersion in normothermic water immediately after the recooling episode. In neither of these experiments did the rewarming treatment artifactually increase the activity of control animals. That the presentation of cold body temperature cues after an erasure treatment would again provide access to the target memory was also suggested in Experiment 1B. Experiment 2 confirmed this effect; over multiple test sessions animals displayed recovery from amnesia, erasure of the recovery effect, and recovery from erasure, in accordance with the availability of cold state cues. Multiple test sessions produced no memory recovery in control animals. Reactivation was not based upon stress per se as exposure to temperature extremes in recooling/rewarming failed to alleviate amnesia. In the present paradigm memory retrieval appears importantly linked to temperature-related contextual cues.     

Modulation by peripheral conditioning stimuli of the responses of trigeminal brain stem neurones and of the jaw opening reflex to tooth pulp stimulation in chronically prepared, anaesthetized cats.

The effects of peripheral conditioning stimuli on the thresholds of the jaw opening reflex (JOR) and of trigeminal brain stem neurones to tooth pulp stimulation were examined in chronically prepared, anaesthetized cats. High intensity electrical conditioning stimuli applied to the ipsilateral forepaw produced an increase in the thresholds of both responses, with the JOR thresholds being elevated significantly more, and remaining elevated for significantly longer, than those of the neurones. These findings suggest that the elevation of the JOR cannot be explained just by inhibitory effects on the brain stem neurones.     

Modulation of TNF-alpha secretion in peripheral blood mononuclear cells by cocoa flavanols and procyanidins

Epidemiological reports have suggested that the consumption of foods rich in flavonoids is associated with a lower incidence of certain degenerative diseases, including cardiovascular disease. Flavanols and their related oligomers, the procyanidins CFP, isolated from cocoa can modulate the production and level of several signaling molecules associated with immune function and inflammation in vitro, including several cytokines and eicosanoids. To further elucidate the potential immuno-modulatory functions of flavanol-rich cocoa, the present investigation examined whether isolated CFP fractions (monomers through decamers) influence the secretion of tumor necrosis factor-alpha (TNF-alpha) from resting and phytohemagluttinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC). We used an in vitro culture system where PBMC from 14 healthy subjects were introduced to individual CFP fractions for 72 h prior to measuring the levels of TNF-alpha released. The intermediate-sized CFP fractions (tetramers through octamers) were the most active on resting cells, causing a 3-4 fold increase in TNF-alpha relative to media baseline. The monomers and dimers were the least stimulatory of the fractions tested, displaying a 42 and 31% increase, respectively, over media control, whereas the trimers, nonamers and decamers showed an intermediate stimulation of this cytokine. In the presence of PHA, the intermediate-sized CFP fractions again were the most active, enhancing TNF-alpha secretion in the range of 48-128% relative to the PHA control. The monomers and dimers were slightly inhibitory (-1.5 and -15%, respectively), while trimers, nonamers and decamers stimulated moderate increases in TNF-alpha levels (13, 19 and 15%, respectively). The above results lend support to the concept that CFP can be immunomodulatory. The stimulation of TNF-alpha secretion may contribute to the putative beneficial effects of dietary flavanoids against microbial infection and tumorigenesis.