On the mechanism of the cortical depression induced by afferent stimulation

The cortical depression induced by the stimulation of some afferent fibers affects strychnine spikes elicited in two different ways: by direct electrical stimulation, and through the evoked potentials induced at the somatosensory area by single shocks to the radial nerve. The effects on these two types of responses were found to be very similar, which was taken to indicate that the site of action of the mechanism involved is the same, that is, the non-synaptic membranes of the dendrites of pyramidal neurons. It is suggested that the depressant action is mediated through the serotonergic neurons, since the previous administration of 5,6-Dihydroxytryptamine (5,6-DHT) blocked the changes. The 5-Hydroxytryptamine (5-HT) liberated would act as a neurohumoral agent, since the synaptic mechanisms do not seem to be involved and the effects are manifested in a diffuse manner.     

Spike suppression in a local cortical circuit induced by transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) noninvasively interferes with human cortical function, and is widely used as an effective technique for probing causal links between neural activity and cognitive function. However, the physiological mechanisms underlying TMS-induced effects on neural activity remain unclear. We examined the mechanism by which TMS disrupts neural activity in a local circuit in early visual cortex using a computational model consisting of conductance-based spiking neurons with excitatory and inhibitory synaptic connections. We found that single-pulse TMS suppressed spiking activity in a local circuit model, disrupting the population response. Spike suppression was observed when TMS was applied to the local circuit within a limited time window after the local circuit received sensory afferent input, as observed in experiments investigating suppression of visual perception with TMS targeting early visual cortex. Quantitative analyses revealed that the magnitude of suppression was significantly larger for synaptically-connected neurons than for isolated individual neurons, suggesting that intracortical inhibitory synaptic coupling also plays an important role in TMS-induced suppression. A conventional local circuit model of early visual cortex explained only the early period of visual suppression observed in experiments. However, models either involving strong recurrent excitatory synaptic connections or sustained excitatory input were able to reproduce the late period of visual suppression. These results suggest that TMS targeting early visual cortex disrupts functionally distinct neural signals, possibly corresponding to feedforward and recurrent information processing, by imposing inhibitory effects through intracortical inhibitory synaptic connections.     

Spatio-temporal analysis of cortical activity evoked by gustatory stimulation in humans.

Gustatory activated regions in the cerebral cortex have not been identified precisely in humans. In this study we recorded the magnetic fields from the brain in response to two tastants, 1 M NaCl and 3 mM saccharin. We estimated the location of areas activated sequentially after the onset of stimulation with magnetic source imaging. We investigated the primary gustatory area (area G) precisely, and found it at the transition between the parietal operculum and the insular cortex. The central sulcus was activated less frequently than area G but with almost the same latency in cases of NaCl stimulation. Following area G, we found activation in several cortical regions, e.g. both the frontal operculum and the anterior part of the insula, the hippocampus, the parahippocampal gyrus and the superior temporal sulcus.     

Diaphragmatic pressures: transvenous vs. direct phrenic nerve stimulation

Diaphragmatic force, determined by stimulating the phrenic nerve while simultaneously measuring the pressures in a closed respiratory system, was assessed in five anesthetized dogs over a 5-h period to evaluate the inherent variability of this technique. Transdiaphragmatic pressure (Pdi) was measured at functional residual capacity during stimulation (120 Hz, 0.2-ms duration) of one phrenic nerve by either direct phrenic nerve stimulation (DPNS) or transvenous phrenic nerve stimulation (TPNS). An analysis of variance showed no significant (P greater than 0.50) change during the 5-h period. There was a significant correlation (r = 0.94, P less than 0.001) between Pdi obtained by TPNS and that obtained by DPNS. It is concluded that either DPNS or TPNS can be used to evaluate diaphragmatic strength over a 5-h period and that TPNS can be used in lieu of DPNS.     

Comparison of the temporal properties of medium latency responses induced by cortical and peripheral stimulation

Sudden foot dorsiflexion lengthens soleus muscle and activates stretch-based spinal reflexes. Dorsiflexion can be triggered by activating tibialis anterior (TA) muscle through peroneal nerve stimulation or transcranial magnetic stimulation (TMS) which evokes a response in the soleus muscle referred to as Medium Latency Reflex (MLR) or motor-evoked potential-80 (Soleus MEP80), respectively. This study aimed to examine the relationship between these responses in humans. Therefore, latency characteristics and correlation of responses between soleus MEP80 and MLR were investigated. We have also calculated the latencies from the onset of tibialis activity, i.e., subtracting of TA-MEP from MEP80 and TA direct motor response from MLR. We referred to these calculations as Stretch Loop Latency Central (SLLc) for MEP80 and Stretch Loop Latency Peripheral (SLLp) for MLR. The latency of SLLc was found to be 61.4 ± 5.6 ms which was significantly shorter (P = 0.0259) than SLLp (64.0 ± 4.2 ms) and these latencies were correlated (P = 0.0045, r = 0.689). The latency of both responses was also found to be inversely related to the response amplitude (P = 0.0121, r = 0.451) probably due to the activation of large motor units. When amplitude differences were corrected, i.e. investigating the responses with similar amplitudes, SLLp, and SLLc latencies found to be similar (P = 0.1317). Due to the identical features of the soleus MEP80 and MLR, we propose that they may both have spinal origins.     

Muscle enhancement using closed-loop electrical stimulation: volitional versus induced torque.

In cases of partial deficiency of muscle activation capacity, force augmentation can be achieved by hybrid activation, i.e., by combining electrical stimulation (ES) with volitional activation. In this activation modality the shares of the volitional and induced torques within the overall hybrid torque are unknown. The purpose of this study was to suggest a computational approach to parcel out the volitional and stimulation induced components of joint torque generated during combined voluntary and electrical activation of the Tibialis Anterior muscle (TA). For this purpose, isometric contraction of the TA was studied on 5 healthy subjects, using an activation protocol involving ES alone, volitional activation alone and hybrid activation. Ankle torque and TA EMG were measured. A computational algorithm was developed to dissociate the volitional from the overall torque, based on EMG filtering and on pre-measured calibration curves of volitional torque versus EMG. The results indicated that for a certain hybrid torque there is a linear decaying relationship between the induced torque and the volitional torque shares. Moreover, based on a defined enhancement ratio, the results indicate that within the range of stimulation intensities, there exist regions of increased facilitation, in which the stimulation efficiency is higher under combined compared to isolated conditions.     

Source localization of induced cortical oscillations during tactile finger stimulation.

We investigated the EEG beta event-related synchronization (ERS) after tactile finger stimulation in three subjects. Prior studies from our group using electrical stimulation and self-paced movement showed a beta rebound within one second after stimulation respectively movement offset. As the tactile-stimulation-data showed a similar ERS behaviour, we extracted the cortical sources for this beta rebound by the linear estimation method in order to see whether the representation areas of different fingers were distinguishable (as is possible with MEG data). Although realistic head models of two subjects were used for the calculations the fingers could not be spatially distinguished. However, regarding the whole spatio-temporal pattern of the ERS for different fingers clear differences can be observed.     

Pharmacological characterization of lower esophageal sphincter relaxation induced by swallowing, vagal efferent nerve stimulation, and esophageal distention.

To characterize the neural pathways involved in lower esophageal sphincter relaxation, intraluminal pressures from the lower esophageal sphincter of the opossum were monitored during swallowing, vagal efferent nerve stimulation, and intraluminal balloon distention in the presence and absence of pharmacologic antagonism of putative neurotransmitters. The combination of atropine, hexamethonium, and 5-methoxydimethyltryptamine, which is known to block ganglionic transmission in the vagal inhibitory pathway to the lower esophageal sphincter, significantly antagonized LES relaxation induced by both swallowing and vagal stimulation, but did not affect the LES relaxation induced by balloon distention. Administration of the nitric oxide synthase inhibitor N omega nitro-L-arginine methyl ester, on the other hand, markedly inhibited LES relaxation induced by vagal stimulation, swallowing, and balloon distention, and this effect was reversed by administration of the nitric oxide synthase substrate L-arginine. These studies indicate that the distension-induced intramural pathway mediating LES relaxation does not involve ganglionic transmission similar to that of the vagal inhibitory pathway to the LES. However, the LES relaxation induced by all forms of stimuli appears to depend on nitric oxide as a final mediator.     

Reproducibility of human brain activity evoked by esophageal stimulation using functional magnetic resonance imaging

Functional MRI is a popular tool for investigating central processing of visceral pain in healthy and clinical populations. Despite this, the reproducibility of the neural correlates of visceral sensation by use of functional MRI remains unclear. The aim of the present study was to address this issue. Seven healthy right-handed volunteers participated in the study. Blood oxygen level-dependent contrast images were acquired at 1.5 T while subjects received nonpainful and painful phasic balloon distensions ("on-off" block design, 10 stimuli per "on" period, 0.3 Hz) to the distal esophagus. This procedure was repeated on two further occasions to investigate reproducibility. Painful stimulation resulted in highly reproducible activation over three scanning sessions in the anterior insula, primary somatosensory cortex, and anterior cingulate cortex. A significant decrease in strength of activation occurred from session 1 to session 3 in the anterior cingulate cortex, primary somatosensory cortex, and supplementary motor cortex, which may be explained by an analogous decrease in pain ratings. Nonpainful stimulation activated similar brain regions to painful stimulation, but with greater variability in signal strength and regions of activation between scans. Painful stimulation of the esophagus produces robust activation in many brain regions. A decrease in subjective perception of pain and brain activity from the first to the final scan suggests that serial brain imaging studies may be affected by habituation. These findings indicate that for brain imaging studies that require serial scanning, development of experimental paradigms that control for the effect of habituation is necessary.