Reflex receptive fields for human withdrawal reflexes elicited by non-painful and painful electrical stimulation of the foot sole.

OBJECTIVES: Human withdrawal reflex receptive fields (RRFs) were assessed for 4 different electrical stimulus intensities, ranging from below the pain threshold (PTh) to up to two times the PTh intensity (0.8x, 1.2x, 1.6x, and 2.0xPTh). METHODS: Thirteen subjects participated, and the reflexes were recorded in a sitting position. The stimuli were delivered in random order to 12 positions distributed over the foot sole. Tibialis anterior (TA), gastrocnemius medialis (GM), vastus lateralis (VL), and biceps femoris (BF) reflexes were recorded. Further, knee and ankle joint angle changes were recorded. RESULTS: The strongest reflexes were seen in the TA compared with the other 3 muscles. Dorsi-flexion dominated distal to the talocrural joint corresponding to the TA receptive field area. An expansion of the RRF for the TA and GM was seen when increasing the stimulus intensity from 0.8xPTh to 1.2xPTh and from 1.2xPTh to 1.6xPTh, indicating a gradually increasing reflex threshold towards the border, where TA contraction is inappropriate in a withdrawal reaction. For the BF and VL, the borders of the RRF areas were not detected. By integrating the reflex size within the RRF (i.e. the reflex volume), gradually increasing reflexes for increasing stimulus intensity were seen in all 4 muscles tested, most clearly in the TA and GM. The subjective pain intensity correlated to the reflex volume for the TA, GM, and BF. CONCLUSIONS: In conclusion, the highest reflex sensitivity was seen in the centre of the RRF, while the stimulus intensity needed for eliciting a reflex increased towards the receptive field border. Within the RRF, stronger reflexes were evoked for increasing stimulus intensity. The limit in the size of the receptive field size for the TA and GM supports a modular withdrawal reflex organisation.     

Modular organization of excitatory and inhibitory reflex receptive fields elicited by electrical stimulation of the foot sole in man.

OBJECTIVES: The present study aimed to investigate how the inhibitory and excitatory reflex components of the human (polysynaptic) withdrawal reflex are organized depending on the stimulation site. The reflexes were elicited during a voluntary pre-contraction (between 10 and 20% of maximum voluntary contraction) of two antagonistic muscles. METHODS: Inhibitory and excitatory reflex receptive fields to tibialis anterior (TA) and soleus (SO) were mapped in 14 healthy subjects using randomized electrical stimulation at 16 sites of the foot sole. Low, non-painful (3x perception threshold), and high, painful (1.5x pain threshold), stimulus intensities were used. RESULTS: The inhibitory reflex receptive fields were organized in a highly functional manner supporting the action of the excitatory reflex. Together the two reflexes result in an optimal withdrawal from the stimulus. Low stimulation intensity was found sufficient to elicit the inhibitory reflex. High stimulation intensity caused a reversal of the inhibition to excitation in tibialis anterior. In soleus the inhibition was facilitated for stronger intensities. CONCLUSION: In conclusion, findings in animals of a modular organization of inhibitory reflexes are reproduced in humans.     

Posterior root-muscle reflexes elicited by transcutaneous stimulation of the human lumbosacral cord

Continuous epidural stimulation of lumbar posterior root afferents can modify the activity of lumbar cord networks and motoneurons, resulting in suppression of spasticity or elicitation of locomotor-like movements in spinal cord-injured people. The aim of the present study was to demonstrate that posterior root afferents can also be depolarized by transcutaneous stimulation with moderate stimulus intensities. In healthy subjects, single stimuli applied through surface electrodes placed over the T11-T12 vertebrae with a mean intensity of 28.6 V elicited simultaneous, bilateral monosynaptic reflexes in quadriceps, hamstrings, tibialis anterior, and triceps surae by depolarization of lumbosacral posterior root fibers. The nature of these posterior root-muscle reflexes was demonstrated by the duration of the refractory period, and by modifying the responses with vibration and active and passive movements. Stimulation over the L4-L5 vertebrae selectively depolarized posterior root fibers or additionally activated anterior root fibers within the cauda equina depending on stimulus intensity. Transcutaneous posterior root stimulation with single pulses allows neurophysiological studies of state- and task-dependent modulations of monosynaptic reflexes at multiple segmental levels. Continuous transcutaneous posterior root stimulation represents a novel, non-invasive, neuromodulative approach for individuals with different neurological disorders.     

Withdrawal reflexes in adductor muscles elicited by electrical and magnetic stimulation of the obturator nerve

The withdrawal reflex in the short head of the biceps femoris muscle after electrical stimulation of the sural nerve at the ankle has been investigated in numerous studies. These studies have described two distinct responses: early (R-II) and late (R-III). However, withdrawal reflex activity of the adductor muscles in the legs has not been studied systematically. Adductor muscle reflex activity is important because it can produce serious clinical problems, such as adductor spasticity and spasms, during bladder surgery. The present study examined withdrawal reflex features of adductor muscles obtained by electrical and magnetic stimulation of the obturator nerve (ON) in 34 normal healthy subjects. Early adductor muscle withdrawal reflex responses were elicited by ipsilateral ON electrical stimulation with a mean latency of 45.7+/-2.0 ms (responses in 94% of subjects). Reflex responses were also obtained using magnetic stimulation at a similar incidence rate. Contralateral ON electrical stimulation resulted in a similar reflex, but with a lower incidence. ON and femoral nerve electrical and magnetic coil stimulation produced similar low-incidence responses in the vastus medialis. These findings indicate that short latency adductor withdrawal reflexes are easily obtained on both sides following electrical or magnetic stimulation of the ON, and they can be elicited by both nociceptive and nonnociceptive stimuli. These reflexes prepare the body for a proper response to incoming signals and likely serve to protect the pelvic floor and pelvic organs.     

Intense peripheral electrical stimulation differentially inhibits tail vs. limb withdrawal reflexes in the rat

In an on-going study on mechanisms by which activation of sensory afferents regulates nociception, high-intensity, low-frequency electrical stimulation was applied to previously defined meridian and non-meridian points of the hindlimb or forelimb, and the effects measured on the withdrawal reflex of the tail or limb in the lightly anesthetized rat. Withdrawal was evoked by application of noxious radiant heat to the tip of the tail or to the plantar surface of a hindpaw or forepaw. Parameters of conditioning electrical stimulation were 2 ms pulses at 4 Hz for 20 min at 20 × threshold (20–30 mA) where threshold was the minimum intensity which evoked muscle twitch. In experiments on tail withdrawal, stimulation applied to meridian points fengshi (GB-31), femur-futu (ST-32) and zusanli (ST-36) of the hindlimb or to wai-kuan (TH-5) and hoku (LI-4) of the forelimb increased the latency of the withdrawal reflex to 70–100% of the maximum possible inhibition (MPI) during the stimulation. Inhibition persisted for more than 1 h after the end of stimulation. Bilateral stimulation of hindlimb meridian points evoked a greater inhibition during the stimulation ( > 95% of the MPI); the inhibition persisted for 40 min. Stimulation of non-meridian sites in hindlimb or forelimb inhibited the withdrawal reflexes by 45–50% of the MPI during the stimulation only. Thus, the evoked inhibition has two components, a brief effect elicited by non-meridian point stimulation and a persistent post-stimulation effect produced only upon stimulation of meridian points. Stimulation produced little effect on nociceptive limb withdrawal reflexes. The results suggest that high-intensity, low-frequency electrical stimulation of meridian points produced a long-lasting, extrasegmental inhibition of the tail withdrawal but not of limb withdrawal reflexes. This differential inhibition may be due to differences in neuronal circuitry and CNS modulatory control mechanisms. The persistent inhibition appears to be dependent on the site of stimulation because it is not evoked by stimulation of sites outside of meridian points.     

Inhibition by transcutaneous electrical stimulation of noxious heat elicited in human Gasserian ganglion.

During percutaneous thermocoagulation of the Gasserian ganglion for trigeminal pain, the pain perception threshold was established in a series of 25 awake patients by measuring the temperature at the electrode tip within the ganglion during slow increase of the radiofrequency current. Between 42 and 48 degress C pain perception was regularly reported by the patients. A cutaneous-stimulating system was then applied to the trigeminal area which was reported to be painful during the heating. The external stimulation attempted to preferentially stimulate the A afferent nerve fibres. When external stimulation was applied during the heating of the Gasserian ganglion, the pain perception threshold was enhanced in about half of the cases. A transcutaneous electrical stimulation of part of the body not related with the investigated pain sensation did not produce the same inhibitory action in 3 out of 5 cases.     

Trigeminocervical reflexes elicited by stimulation of the infraorbital nerve: head retraction reflex.

In the current study, the effects of stimulation of the infraorbital nerve (ION) on the trigeminocervical reflexes (TCRs), recorded from the posterior neck muscles, was investigated and the results were compared with the results recorded by stimulation of the supraorbital nerve (SON). TCRs obtained by stimulation of the ION was evaluated as the electrophysiologic counterpart of the head retraction reflex. Twenty normal control subjects, 10 men and 10 women, were enrolled in the study. The SON and the ION were stimulated by using a bipolar surface electrode. Results were recorded by using either concentric needle electrodes inserted into the semispinalis capitis muscle at the level of the third or fourth cervical vertebra or by surface electrodes placed at the C3 and C7 vertebrae on the midline. It was found that stimulation of the supraorbital and infraorbital branches of the trigeminal nerve had different reflexive effects on the posterior neck muscles. A stable positive (or negative-positive) wave, with a very early latency and high amplitude was always recorded after maximal stimulation of the ION, which could never be detected by stimulation of the SON. The C3 response of the TCR, evoked by SON stimulation was always evoked, by stimulation of the ION, at a low threshold. These findings suggest that the head retraction reflex is composed of two phases: inhibitory and excitatory. The early, fixed positive wave represents the general inhibition of the cranial and neck muscles, just before withdrawal of the face and head, from unexpected stimuli, which precedes the dense C3 response, demonstrating activation of the posterior neck muscles.     

Depression of the human nociceptive withdrawal reflex by segmental and heterosegmental intramuscular electrical stimulation.

OBJECTIVE: To investigate the effects of intramuscular electrical conditioning in the modulation of nociceptive withdrawal reflex (NWR) and further to determine what muscle afferents are involved in the modulation of the nociceptive withdrawal reflex and the sites along the reflex pathway where the NWR modulation occurs in healthy humans. METHODS: The NWR elicited by a cutaneous test stimulus to the dorsal foot was modulated by a short (21 ms) intramuscular conditioning electrical stimulus at two times the pain threshold. At varying conditioning-test stimulus intervals, segmental conditioning stimulus was applied in the tibialis anterior muscle ipsilateral and contralateral to the test stimulus, and heterosegmental conditioning stimulus was applied in the contralateral trapezius muscle to modulate the NWR. Non-painful and painful intramuscular conditioning stimuli were also used to modulate the NWR and the soleus H-reflex. RESULTS: The NWR was depressed by preceding intramuscular conditioning stimuli, with a degree that depended on the conditioning-test stimulus intervals and on the conditioning site. Segmental conditioning depressed the NWR more quickly and gave a longer duration (15-1500 ms), and larger magnitude than heterosegmental conditioning, which depressed the NWR in a short temporal window (80-100 ms). No difference was seen in the magnitude of the NWR depression between the painful and non-painful intramuscular stimuli, and the soleus H-reflex was not affected. CONCLUSIONS: Our results suggest that segmental and heterosegmental conditionings of NWR are mediated by myelinated muscle afferents engaging central inhibitory mechanisms rather than direct changes in the excitability of motor neurons. SIGNIFICANCE: The therapeutic effects of electrotherapy could involve these mechanisms in the treatment of muscle pain syndromes.     

Human masseter inhibitory reflexes evoked by repetitive electrical stimulation.

OBJECTIVES: The relationship between the masseter inhibitory reflex (MIR) and nociceptive processing in the trigeminal region was studied in 10 healthy subjects. Based on the known increase in perceived sensory intensity following repetitive stimulation of the nociceptive system, we examined the hypothesis that the MIR reflects noxious activity in the trigeminal system by determining the possible relation between changes in MIR and perceived sensory intensity. METHODS: The MIR was quantitated and compared with psychophysical measures following repetitive peri-oral electrical stimulation (5 square wave pulses of 0.5ms repeated at 2Hz). In addition to the early (ES1) and late (ES2) periods of exteroceptive suppression, two periods with apparent excitation could be distinguished from the background electromyografical activity: (a) the inter-suppression period (ISP) between the ES1 and the ES2, and (b) the post-suppression period (PSP) after the ES2. A computer algorithm was used to detect and quantitate ES1, ES2, ISP, and PSP. The response variables were (a) onset latencies and (b) magnitudes of suppression (ES1 and ES2) and excitation (ISP and PSP). RESULTS: Consistent reduction of the magnitude of ES2 suppression in response to repetitive stimuli was observed below as well as above the pain detection threshold. CONCLUSIONS: The observed reduction of the magnitude of ES2 suppression is not specifically related to nociceptive processing. Habituation or net inhibitory effects on inhibitory pre-motor neurones (i.e. disinhibition) are possible mechanisms for the observed reduction of the magnitude of ES2 suppression after repetitive stimulation.     

Functional organization of human supplementary motor cortex studied by electrical stimulation

The presence of somatotopic organization in the human supplementary motor area (SMA) remains a controversial issue. In this study, subdural electrode grids were placed on the medial surface of the cerebral hemispheres in 13 patients with intractable epilepsy undergoing evaluation for surgical treatment. Electrical stimulation mapping with currents below the threshold of afterdischarges showed somatotopic organization of supplementary motor cortex with the lower extremities represented posteriorly, head and face most anteriorly, and the upper extremities between these two regions. Electrical stimulation often elicited synergistic and complex movements involving more than one joint. In transitional areas between neighboring somatotopic representations, stimulation evoked combined movements involving the body parts represented in these adjacent regions. Anterior to the supplementary motor representation of the face, vocalization and speech arrest or slowing of speech were evoked. Various sensations were elicited by electrical stimulation of SMA. In some cases a preliminary sensation of "urge" to perform a movement or anticipation that a movement was about to occur were evoked. Most responses were contralateral to the stimulated hemisphere. Ipsilateral and bilateral responses were elicited almost exclusively from the right (nondominant) hemisphere. These data suggest the presence of combined somatotopic organization and left-right specialization in human supplementary motor cortex.     

Aphasia elicited by electrical stimulation of the right anterior corpus callosum

Background: The preoperative evaluation of drug-resistant focal epilepsy patients considered for epilepsy surgery provides a unique setting to evaluate cortical function and corresponding networks.

Aims: Whereas there is a wealth of data on cortical language localization using electrical stimulation with subdural electrodes, there is much less experience with stimulation of depth electrodes in the white matter and an effect on language function via electric stimulation of the corpus callosum has not been demonstrated so far.

Methods & Procedures: We report on a 29-year-old epilepsy patient with bilateral language representation who underwent pre-surgical EEG-video-monitoring for drug-resistant, non-lesional right frontal lobe epilepsy.

Outcomes & Results: Electric stimulation of a stereotactically implanted depth electrode in the right anterior corpus callosum elicited paraphasia and anomia. The precise mechanism could be an inhibition of cortical language areas in the left hemisphere, the right hemisphere or interference with transcallosal connectivity.

Conclusions: This is the first report on language dysfunction through electric stimulation in the corpus callosum, most likely through an inhibition of cortical language areas in the left frontal lobe.     

Characteristics of sympathetic reflexes evoked by electrical stimulation of phrenic nerve afferents.

In chloralose-anaesthetized cats, sympathetic reflex responses were recorded in left cardiac and renal nerve during stimulation of afferent fibres in the ipsilateral phrenic nerve. In cardiac nerve, a late reflex potential with a mean onset latency of 75.6 +/- 13.8 ms was regularly recorded which, in 20% of the experiments, was preceded by an early, very small reflex component (latency between 35 and 52 ms). In contrast, in renal nerve only a single reflex component after a mean latency of 122.1 +/- 13.1 ms was observed. Bilateral microinjections of the GABA-agonist muscimol into the rostral ventrolateral medulla oblongata resulted in a nearly complete abolition of sympathetic background activity and in an 88% reduction of the late reflex amplitude with only small effects on the latency of the evoked potentials. Under this condition, an early reflex component was never observed to appear. After subsequent high cervical spinalization, the residual small potentials which persisted after bilateral muscimol injections were completely abolished and in cardiac nerve an early reflex potential with a mean latency of 45 +/- 10 ms was observed in all but one experiment. The early reflex was therefore referred to as a spinal reflex component which, however, is suppressed in most animals with an intact neuraxis. In the renal nerve a spinal response was only observed in one experiment after spinalization. The results suggest that sympathetic reflexes evoked by stimulation of phrenic nerve afferent fibres possess similar spinal and supraspinal pathways as previously described for somato-sympathetic and viscero-sympathetic reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition of withdrawal responses by pelvic nerve electrical stimulation

In urethane-anesthetized rats, the compound action potential of the pelvic nerve was found to consist of three different waves, two in the Aδ fiber and one in the C-fiber range of conduction velocity. Electrical stimulation of the pelvic nerve produced a complete inhibition of the withdrawal response to noxious foot pinch or foot compression. The electromyographic (EMG) activity of the contralateral posterior biceps muscle was used to record the withdrawal response. The withdrawal response inhibition was related to the duration and the frequency of electrical stimulation. Low (5–10 Hz) and high (100–300 Hz) frequencies were ineffective in inhibiting the withdrawal response, whereas intermediate frequencies (20–80 Hz) produced a complete inhibition of the withdrawal response. Short (300 ms) trains of stimulation inhibited the withdrawal response only during the stimulation period. Longer trains of stimulation (500 ms-10 s) produced long-lasting inhibition of the response to noxious stimulation. The inhibition persisted for up to 20 s after the end of electrical stimulation of the pelvic nerve. Aδ fiber stimulation was adequate to inhibit the withdrawal response in most (15 out of 17) of the animals. However, Aδ plus C-fiber stimulation was needed to inhibit the response to noxious stimulation in two animals. In addition to inhibiting the response to noxious stimulation, pelvic nerve electrical stimulation reflexively activated abdominal muscles. On the basis of present findings using electrical stimulation, it can be suggested that, in the rat, Aδ and C-visceral afferents of the pelvic nerve mediate the analgesic effect of vaginocervical probing pelvic and Aδ afferents the contraction of abdominal muscles in the fetus-expulsion reflex.     

Cerebrovascular changes elicited by electrical stimulation of the centromedian-parafascicular complex in rat

Electrical stimulation of the centromedian-parafascicular complex (CM-Pf) in anesthetized (chloralose) and paralyzed (tubocurarine) rats elicites a widespread cerebrovascular dilatation. Regional cerebral blood flow (rCBF) was measured in dissected tissue samples of 10 brain regions (medulla, pons, cerebellum, inferior colliculus, superior colliculus, frontal parietal and occipital cortices, caudate-putamen and corpus callosum) by [¹⁴C]iodoantipyrine method. In unstimulated and sham-operated rats rCBF ranged from 40±3 (ml/100g/min) in corpus callosum to 86±6 (ml/100g/min) in inferior colliculus. During CM-Pf stimulation, rCBF increased significantly P < 0.05, analysis of variance and Scheffe's test) in all cerebral regions bilaterally ranging from +118% in parietal cortex to +38% in cerebellum. Although cerebral vasodilation elicited by CM-Pf stimulation persisted after unilateral transection of the cervical sympathetic trunk, the cortical CBF was significantly reduced (P < 0.05) on the denervated side. Acute adrenalectomy significantly (P < 0.05) decreased elevated rCBF during CM-Pf stimulation in all cortical regions (frontal −36%, parietal −34%, and occipital −27%) and in caudate nucleus (−37%). Thus, excitation of neurons originating in, or fibers passing through the CM-Pf can elicit a powerful cerebral vasodilation. The cerebral vasodilation is modulated by cervical sympathectomy and circulating adrenal hormones. We conclude that CM-Pf elicited vasodilation is at least partly mediated by intrinsic neural pathways.     

Focal clonus elicited by electrical stimulation of the motor cortex in humans

Focal clonic seizures are a frequent epileptic phenomenon. However, there are little data about their pathomechanism. In four patients with focal epilepsy and subdural electrodes, focal clonus was elicited by electrical stimulation of the motor cortex. Three additional patients underwent intraoperative stimulation of the spinal cord. Rhythmic clonic muscle responses were elicited by cortical stimulation with 20-50 Hz. The clonus consisted of simultaneous trains of compound muscle action potentials (CMAP) in agonistic and antagonistic muscles alternating with periods of muscular silence despite continuous stimulation. Clonus frequency decreased from 4.0-8.0 Hz at 50 Hz stimulation to 3.0-3.5 Hz at 20 Hz paralleled by a prolongation of the trains of CMAP. The stimulation frequency correlated with the number of stimuli blocked during relaxation. During the stable stimulation periods, the clonus frequency decreased over time. The number of stimuli which formed a train of CMAP and which were blocked during relaxation increased towards the end of the stimulation periods. Increasing intensity of stimulation at the same frequency converted a clonic to a tonic response. There was always an 1:1 relationship between stimulus and CMAP during spinal cord stimulation. We hypothesize that during cortical stimulation, clonus is elicited by synchronous activation of pyramidal tract (PT) neurons which results in excitation of intracortical GABA(B)ergic interneurons by recurrent axon-collaterals. This leads to stepwise hyperpolarization of PT neurons intermittently suppressing the output of PT neurons despite continuous stimulation. This mechanism can explain our finding that temporal and spatial summation of the stimuli were needed for clonus generation.     

Autonomic nervous reflexes in respiration elicited by mechanical stimulation of the velopharyngeal region in rabbits

Reflex increases in peak activity of the diaphragm and expiratory pharyngeal muscles were recorded in lightly anesthetized and vagotomized rabbits by gentle mechanical stimulation of the nasal surface of the soft palate and of the posterior wall of the nasopharynx. No noticeable change in diaphragmatic activity was evoked by gentle mechanical stimulation of the oral surface of the soft palate and of the posterior wall of the oropharynx. The present results suggest that afferent signals from mechanoreceptors of the velopharyngeal region may contribute to reflex augmentation of respiration.     

Spatial organization of human perioral reflexes

Reflex responses recorded from the upper and lower divisions of the human orbicularis oris muscle were studied as a function of the site of stimulation. Stimuli were applied to 11 sites, ranging from the glabrous skin of the upper and lower lip vermilion borders to the hairy skin of the cheek. Highly localized, innocuous mechanical stimuli were created by displacing a servo-controlled probe over the surface of the perioral skin. Reflex response amplitude was strongly dependent on the site of stimulation. Stimulation of some sites, for example the ipsilateral corner of the mouth, the chin, and cheek, produced no responses, whereas stimulation of other sites, particularly the ipsilateral vermilion borders, produced large reflex responses. Changes in response amplitude as a function of stimulation site were the same for the upper lip and lower lip muscle recordings, with the largest responses at both recording sites produced by stimulation of the ipsilateral upper lip vermilion border. These results suggest that the upper and lower divisions of orbicularis oris share common synaptic drive, at least from inputs generated via reflex pathways, and that the upper vermilion border may be more densely innervated with mechanoreceptors than the lower. The latter hypothesis was supported by an additional experiment examining two-point discrimination thresholds for the glabrous skin of the upper and lower lips. Two-point thresholds were significantly smaller for the upper compared with the lower lip vermilion border.