Monophasic and biphasic stimulation evoke different responses

In 31 subjects, psychophysiological sensory perception threshold and the waveform of orthodromic sensory nerve action potentials (SNAPs) produced by constant-current 100-micros monophasic negative pulses were compared to those produced by biphasic (negative-positive) symmetrical pulses (100-micros per phase). In addition, the effects of 200-micros monophasic negative pulses were studied. Graded stimuli were delivered to the index finger, and SNAPs were recorded over the median nerve at the wrist. Perception threshold was significantly different among the three conditions. Furthermore, in 26 subjects, at the lower intensities at which SNAPs first appeared, the evoked potential waveform had two small negative phases with biphasic stimuli, but a single negative phase in response to monophasic pulses. At higher stimulus intensities, all SNAPs had a single large negative phase regardless of the stimulus. These perception and waveform findings suggest that, contrary to historical belief, the trailing positive phase of a biphasic pulse has a stimulating effect at low stimulus intensities.     

Physiology of perception: cortical stimulation and recording in humans

OBJECTIVES: 1) To determine the effect of stimulus train duration (TD) on sensory perception using direct stimulation of somatosensory and visual cortices. 2) To investigate the occurrence of evoked potentials in response to stimulation that is subthreshold for perception. BACKGROUND: Studies of the mechanisms of conscious perception using direct cortical stimulation and recording techniques are rare. The clinical necessity to implant subdural electrode grids in epilepsy patients undergoing evaluation for surgery offers an opportunity to examine the role of stimulus parameters and evoked potentials in conscious perception. METHODS: Subjects included epilepsy patients with grids over somatosensory or occipital cortex. Single pulses (100 microseconds) and stimulus trains were applied to electrodes, and thresholds for perception were found. Evoked potentials were recorded in response to peripheral stimulation at intensities at, above, and below sensory threshold. RESULTS: During cortical stimulation, sensory threshold changed little for stimulus trains of 250 milliseconds and longer, but increased sharply as TD decreased below this level. Primary evoked activity was recorded in response to peripheral stimulations that were subthreshold for conscious perception. CONCLUSIONS: The results confirm a previous report of the effects of stimulus TD on sensory threshold. However, no motor responses occurred following somatosensory stimulation with short trains, as previously reported. The TD threshold pattern was similar in visual cortex. In agreement with the previous report, early components of the primary evoked response were not correlated with conscious sensory awareness.     

Quantitative sensory testing of thermal and vibratory perception in familial dysautonomia

Familial dysautonomia (FD) is an inherited disorder that is known to affect both sensory and autonomic functions as a result of incomplete neuronal development and progressive loss but the degree to which patients are affected differs greatly. To determine if quantitative vibration and thermal testing refined the assessment of severity, 23 familial dysautonomia patients were evaluated by clinical examination, measurements of median, peroneal and sural nerve conduction velocities (NCV), and assessment of vibration thresholds at two body sites and of warm and cold perception thresholds at 6 body sites using the method of limits. Data from 80 age-matched normal individuals provided control data for vibration and temperature thresholds. All familial dysautonomia patients had abnormal thermal thresholds. Vibration perception was abnormal in 20 patients. NCVs were slowed in 8 of 16 patients who agreed to be tested. Abnormalities in thermal thresholds are consistent with the reduction of small nerve fibers in familial dysautonomia. Abnormal vibration thresholds might be due to disturbed conduction of vibratory impulse trains and reflect the degree to which the disorder is progressive. Vibration and thermal sensation testing were better accepted and provided more information than NCV regarding severity of disease.     

Enhanced function in nerve-injured hands after contralateral deafferentation

To explore whether contralateral deafferentation by tourniquet-induced anaesthesia can improve function in a nerve-injured hand, we investigated 14 patients with median or ulnar nerve injuries at wrist level. Deafferentation of the contralateral forearm and hand resulted in significantly improved tactile discrimination, threshold for perception of touch in the injured nerve area and in the area corresponding to the intact nerve in the injured hand, and significantly increased grip strength. Improvements lasted at least 15 min. The results show that hand function after peripheral nerve injury can be temporarily enhanced by manipulation of the process of brain plasticity. Our results may have practical applications in the rehabilitation of peripheral nerve-injured patients.     

Polarity order of biphasic square pulse electric current stimulation of human cochlear nerve: Observations with transtympanic electrodes

Eighteen totally deaf human cochleae were stimulated with biphasic square pulses of current through transtympanic needle electrodes. The thresholds of the 2 polarity orders, + - and - +, were compared for various pulse durations. For a pulse duration of 500 μs the polarity order - + had the lower threshold. For pulse durations of 2 ms and longer, the polarity order + - had the lower threshold. A discussion is given of the significance of the results for finding out the site of cochlear nerve excitation by the stimuli.     

Train duration effects on perception: sensory deficit, neglect, and cerebral lateralization.

The mechanisms of conscious perception are uncertain. In a preliminary study, dramatic effects of train duration on perception in a patient with right brain stroke were noted. In this study, the mechanisms of train duration on perception of peripheral somatosensory stimuli are examined. Subjects included healthy adults and patients with right brain infarctions. Train duration effects on perception were examined in relation to cerebral infarction, handedness, age, elevated peripheral threshold via bupivacaine, and impaired attention via diazepam or scopolamine. Perceptual thresholds to electrical pulses on the hand decreased as train duration increased, but only over the first several hundred milliseconds. Compared to controls, right brain stroke patients showed much greater lowering of threshold in the affected hand as train duration was extended. Age and bupivacaine elevated thresholds, but had little or no influence on train duration effects. Diazepam and scopolamine had no effect on thresholds. Thresholds were lower in the left than right hand of healthy dextral subjects, irrespective of age. Sinistral subjects had less left/right asymmetry. Increased train duration effect in patients is not explained by a primary elevation in threshold or by impaired vigilance. Lower perceptual thresholds in the left hand of healthy dextral subjects is consistent with right cerebral dominance for externally directed attention.     

Sensations evoked from the glabrous skin of the human hand by electrical stimulation of unitary mechanosensitive afferents

A needle microelectrode in the median nerve was used to record impulses from tactile afferent units and to deliver trains of electrical pulses for microstimulation. The findings suggest that the activation of single SA I units produces a sensation of light pressure within a small area located within the receptive field of the unit whereas the activation of RA units seemed to elicit sensations of varying qualities: touch, vibration, and tickle.     

Differentiation of the substrates for analgesia and vocalizations elicited by midbrain stimulation in rats: refractory period estimates

Stimulation of periaqueductal gray sites resulted in both increased latencies to escape heated water with a tail-flick and audible vocalizations. To determine whether these two responses were the result of stimulation of the same substrates, refractory periods were estimated by delivering paired-pulse trains of stimulation. Stimulation consisted of 10 or 20 s trains of single pulses or pulse pairs. The pulse pair frequency threshold for both behaviors was determined for intra-pulse (C-T) intervals of 0.4-10 ms. The ratio of single to double pulse frequency thresholds provided an indication of relative effectiveness of the paired-pulse stimulation. For analgesia, the paired-pulse effectiveness gradually increased between C-T intervals of 2.0 and 5.0 ms, after which asymptotic effectiveness values were obtained. Thus, the estimated refractory period for analgesia was 2.0-5.0 ms. The refractory period estimate for vocalizations was shorter. Effectiveness values increased with a C-T interval of 1.2 ms and reached asymptote with a C-T interval of 2.0 ms. These results suggest that different fibers with overlapping spatial distributions contribute to analgesia and vocalizations produced by midbrain stimulation.     

Interactions between rewarding lateral hypothalamic and aversive nucleus reticularis gigantocellularis stimulation

The interaction between rewarding and aversive consequences of brain stimulation were assessed in two studies. In the first, the frequency threshold for 300 ms trains of combined lateral hypothalamic (LH) and nucleus reticularis gigantocellularis (Gi) stimulation, in which each LH pulse was followed 2 ms later by the Gi one, was determined for one month. Compared to the threshold for trains of single LH pulses, combined LH-Gi stimulation initially increased the frequency threshold; however, this effect reversed within one session and was subsequently maintained for the duration of the study. The aversion produced by Gi stimulation, as measured by latency to escape, was abolished following a single session of LH-Gi pairs. In the second study, a subset of animals received both presentations of combined pulses, LH followed by Gi, and the reverse; the interval between pulses was varied from 0.2 to 6.4 ms. The effectiveness of combined stimulation, determined by the ratio of LH frequency thresholds to that of the LH-Gi ranged from 0 to 50% across animals but the individual effectiveness functions within animals did not vary with different intervals. In addition, the order of presentation of pulses was of no consequence. Thus, not only did exposure to LH stimulation appear to obliterate Gi aversion, but the combination of LH and Gi pulses added to the rewarding effect produced by LH stimulation alone.     

Is Ross syndrome a dysautonomic disorder only? An electrophysiologic and histologic study.

OBJECTIVE: To define the involvement of peripheral nerve fibers in Ross syndrome. METHODS: Mechanical pain perception, tactile and thermal thresholds on hand, foot dorsum, thigh, median nerve orthodromic sensory conduction velocity (SCV) and motor conduction velocity (MCV), sural nerve antidromic SCV, peroneal nerve MCV, H-reflex, F-wave, median, tibial nerve somatosensory evoked potentials (SSEPs), perioral, hand CO(2) laser late (LEPs) and ultralate evoked potentials, sympathetic skin response (SSRs), cardiovascular, Minor sweat, silastic imprint, histamine, photopletysmographic and pupil pilocarpine tests, cutaneous innervation immunohistochemical techniques were studied in 3 patients with Ross syndrome. RESULTS: Quantitative sensory testing showed altered results in patients 1 and 2, and patient 3 had a slight impairment of mechanical pain perception. Nerve conduction, except for a median nerve distal reduction of sensory conduction in patient 1, F-wave and SSEP findings were normal; H-reflex was absent at rest in all patients. Hand LEPs were absent in patient 2, ultralate potentials were absent in patients 1 and 2. Skin biopsy showed a disease duration related reduction of unmyelinated and myelinated sensory fibers and a lack of unmyelinated autonomic fibers in all patients. CONCLUSIONS: Our data suggest that Ross syndrome is a degenerative disorder involving progressive sudomotor fibers, and then epidermal sensory unmyelinated and myelinated fibers.     

Continuous Theta Burst Stimulation of the Supplementary Motor Area: Effect Upon Perception and Somatosensory and Motor Evoked Potentials

BackgroundThe supplementary motor area (SMA) has been implicated in many aspects of movement preparation and execution. In addition to motor roles, the SMA is responsive to somesthetic stimuli though it is unclear exactly what role the SMA plays in a somatosensory network.Objective/HypothesisIt is the purpose of this study to assess how continuous theta burst stimulation (cTBS) of the SMA affects both somatosensory (SEPs) and motor evoked potentials (MEPs) and if cTBS leads to alterations in tactile perception thresholds of the index fingertip.MethodsIn experiment 1, cTBS was delivered over scalp sites FCZ (SMA stimulation) (n = 10) and CZ (control stimulation) (n = 10) in separate groups for 40 s (600 pulses) at 90% of participants' resting motor threshold. For both groups, median nerve SEPs were elicited from the right wrist at rest via electrical stimulation (0.5 ms pulse) before and at 10 min intervals post-cTBS out to 30 min (t = pre, 10, 20, and 30 min). Subjects' perceptual thresholds were assessed at similar time intervals as the SEP data using a biothesiometer (120 Hz vibration). In experiment 2 (n = 10) the effect of cTBS to SMA upon single and paired-pulse MEP amplitudes from the right first dorsal interosseous (FDI) was assessed.ResultscTBS to scalp site FCZ (SMA stimulation) reduced the frontal N30 SEP and increased tactile perceptual thresholds 30 min post-stimulation. However, parietal SEPs and MEP amplitudes from both single and paired-pulse stimulation were unaffected at all time points post-stimulation. cTBS to stimulation site CZ (control) did not result in any physiological or behavioral changes.Conclusion(s)These data demonstrate cTBS to the SMA reduces the amplitude of the N30 coincident with an increase in vibration sensation threshold but does not affect primary somatosensory or motor cortex excitability. The SMA may play a significant role in a somatosensory tactile attention network.     

Comparative study of pain perception and polysynaptic blink reflex responses in man

Stimulation of the first trigeminal branch using a 10 ms train of 5 pulses of 0.1 ms duration is performed on 17 healthy subjects (19-65 years of age) in order to assess the relationship between polysynaptic components of the blink reflex and perceptive and pain thresholds (ths). The mean value of tactile ths (Pth) is 2.22 +/- 0.86 mA; while R2, R3 and pain threshold values are 1.25 +/- 0.34, 3.52 +/- 1.94 and 4.78 +/- 2.77 times the Pth respectively. The pain ths average is 1.47 +/- 0.92 with regard to the R3 threshold. The R2 ths are very close to those of tactile perception, while those of R3 appear significantly related to the pain ths.     

Intestinal sensitivity testing by transmucosal electrical nerve stimulation: stimulus parameters to induce conscious perception

Intestinal sensitivity can be tested using transmucosal electrical nerve stimulation. The aim of this study was to establish the stimulus characteristics that determine perception. In six healthy subjects constant current electrical stimuli were applied via an intrajejunal bipolar electrode while measuring perception. Intensity-response tests with stimuli trains of various frequencies (5 and 100 Hz) and pulse durations (50 and 1000 mus) were performed. All stimuli within the broad range tested induced similar-type abdominal sensations, but the intensity of the stimuli to produce perception differed depending on both pulse duration and frequency. A 20-fold increase in pulse duration decreased the intensity of perceived stimuli by a factor of 0.34 +/- 0.04 (P < 0.05); a similar increase in pulse frequency decreased the intensity by a 0.63 +/- 0.07 factor (P < 0.05). When the frequency and duration concomitantly increased, the stimulus intensity decreased by the product of both factors (0.22 +/- 0.04). Transmucosal electrical nerve stimulation of the intestine induces perception within a broad range of stimuli. However, the intensity of the stimuli required to activate sensory pathways is primarily weighted by the duration rather than by the frequency of the pulses.     

Electrolytic lesions of the habenula attenuate brain stimulation reward

The present experiment used electrolytic lesions in combination with curve-shift scaling to study the functional relation between the habenula and four different brain sites that support operant responding for brain stimulation reward. Rats were implanted with a monopolar stimulation electrode aimed at the lateral hypothalamus, ventral tegmental area, dorsal raphe or median raphe nuclei, and a lesioning electrode in the ipsilateral habenula. Operant nose poking resulted in self-administration of trains of electrical pulses to one of the above stimulation sites. Reward thresholds were derived from response-number curves and defined as the pulse number necessary for half-maximal responding. Rats were tested daily at each of three current intensities that were chosen from individual number-current trade-off functions and that yielded baseline reward thresholds of approximately 10, 20 and 40 pulses/train. Testing resumed 24h after lesioning the habenula (100 muA anodal current, 20-25s) and continued for 3-4 weeks. A total of 19 rats completed the experiment. In five of these, habenular lesions clearly reduced the rewarding effectiveness of the stimulation; reward thresholds increased by approximately 30-245% (0.12-0.54 log10 units). Generally, lesion effects were observed at low and medium current intensities, developed gradually and did not recover. Histological analysis revealed that in two rats the stimulation electrode was located in the posterior lateral hypothalamus, two in the anterior ventral tegmental area and one in the area of the dorsal raphe. These results strongly suggest that the habenula constitutes an important component of the neural circuitry important for brain stimulation reward.     

Perceptual plasticity is mediated by connectivity changes of the medial thalamic nucleus

It is well known that the threshold for somatosensory perception may adapt to different inputs. Recent studies suggest the presence of a modulating effect of somatosensory inputs on the spinal dorsal horn. However, the effects of somatosensory inputs on cerebral processing and, in particular, on the functional and effective connectivity of the somatosensory brain network, are poorly understood. In this study, we investigated the longitudinal impact of somatosensory stimuli on the resting‐state functional connectivity and effective connectivity of the somatosensory brain network. We performed resting‐state functional magnetic resonance imaging (fMRI) in 12 healthy subjects before and after unilateral electrical median nerve stimulation. We combined this analysis with a psychophysiological examination of changes of the perception threshold. We found that the unilateral median nerve stimulation increased the perception thresholds bilaterally and increased the resting‐state functional and effective connectivity between most cortical areas of the somatosensory network. The major finding, however, was a decreased resting‐state functional connectivity between both secondary somatosensory cortices and the bilateral medial nuclear complex of the thalamus. This decreased connectivity was correlated with increased perception thresholds. These findings emphasize the importance of the medial thalamic nucleus for the perceptual awareness of somatosensory stimuli. Hum Brain Mapp 34:2343–2352, 2013. © 2012 Wiley Periodicals, Inc.     

Influence of pulse configuration and direction of coil current on excitatory effects of magnetic motor cortex and nerve stimulation.

This paper describes the influence of pulse configuration and current direction on the excitation of the hand-associated motor cortex and the median nerve by magnetic stimulation. Monophasic and biphasic current pulses with the same peak rise time of 80 micros and a maximum rate of current change (dI/dt) were discharged through an eight-shaped coil of the stimulator used (Dantec MagPro). Two current directions with opposite orientation in the coil axis were studied. FINDINGS: (1) for both, cortex and nerve stimulation, biphasic stimuli were more effective and elicited compound muscle action potentials (CMAPs) with lower thresholds and larger amplitudes. (2) Using biphasic pulses the direction of the currents in the first phase of the pulse did not influence the CMAP amplitude. (3) Using monophasic pulses induced currents oriented postero-anteriorly in the motor cortex or orthodromically along the nerve axis elicited larger CMAPs than currents in the opposite orientation. (4) Pulse configuration did not influence the CMAP-latencies and by this the stimulation site (cortex, nerve). CONCLUSION: Monophasic stimuli are useful to investigate excitation effects which are dependent on the current direction. The application of biphasic stimuli with their stronger excitation effects might be advantageous when patients with high cortical thresholds or deep lying nerves shall be investigated.     

Peripheral neuropathy profile in various groups of diabetics.

The results of applying a battery of peripheral nerve function tests in three groups of diabetics are reported. The tests examined the integrity of all the major subgroups of nerve fibres. The diabetics were grouped according to the clinical severity of their neuropathy: Group I--11 patients with long standing diabetes but clinically insignificant neuropathy, Group II--27 patients with mild neuropathy and Group III--23 patients with neuropathic foot lesions. As expected the incidence of abnormality of all functions increased from Group I to III, but within a group there was no clear pattern of differential involvement of different fibre types. The study has identified those tests that are suitable for detecting early neuropathy (warming and vibration perception thresholds and sensory nerve action potentials) and those which are likely to be useful in assessing deterioration or improvement (particularly vibration perception threshold), but since the different tests cannot be equally matched for sensitivity it is not possible to interpret the results in terms of the degree of pathological involvement of different fibre groups.     

Assessment of nerve regeneration and adaptation after median nerve reconnection and digital neurovascular flap transfer

Six patients with median nerve severance (five sutured) were studied after an interval of 1.8 to 35 years to assess residual neurologic deficit, misdirected axonal regrowth, and adaptation to faulty reinnervation. Mild motor impairment was confirmed by the smaller thenar muscle action potentials and isometric muscle twitches from supramaximal stimulation of the median nerve. Sensory impairment was supported by the increased thresholds of vibratory (p = 0.003) and touch-pressure (p = 0.004) detection thresholds of the pulp of index fingers and decreased amplitudes of sensory nerve action potentials. A tactile hemidigit localization test revealed that localization was not significantly different from that on the contralateral side but perceptual territory was increased. This increase is best explained by misdirected axon regrowth without CNS adaptation. Long-standing faculty tactile digit localization in neurovascular skin flaps from finger to thumb also was demonstrated--further evidence that CNS adaptation is imperfect when sensory nerves to digits are relocated.     

Homeostatic metaplasticity in the human somatosensory cortex

Long-term potentiation (LTP) and long-term depression (LTD) are regulated by homeostatic control mechanisms to maintain synaptic strength in a physiological range. Although homeostatic metaplasticity has been demonstrated in the human motor cortex, little is known to which extent it operates in other cortical areas and how it links to behavior. Here we tested homeostatic interactions between two stimulation protocols -- paired associative stimulation (PAS) followed by peripheral high-frequency stimulation (pHFS) -- on excitability in the human somatosensory cortex and tactile spatial discrimination threshold. PAS employed repeated pairs of electrical stimulation of the right median nerve followed by focal transcranial magnetic stimulation of the left somatosensory cortex at an interstimulus interval of the individual N20 latency minus 15 msec or N20 minus 2.5 msec to induce LTD- or LTP-like plasticity, respectively [Wolters, A., Schmidt, A., Schramm, A., Zeller, D., Naumann, M., Kunesch, E., et al. Timing-dependent plasticity in human primary somatosensory cortex. Journal of Physiology, 565, 1039-1052, 2005]. pHFS always consisted of 20-Hz trains of electrical stimulation of the right median nerve. Excitability in the somatosensory cortex was assessed by median nerve somatosensory evoked cortical potential amplitudes. Tactile spatial discrimination was tested by the grating orientation task. PAS had no significant effect on excitability in the somatosensory cortex or on tactile discrimination. However, the direction of effects induced by subsequent pHFS varied with the preconditioning PAS protocol: After PAS(N20-15), excitability tended to increase and tactile spatial discrimination threshold decreased. After PAS(N20-2.5), excitability decreased and discrimination threshold tended to increase. These interactions demonstrate that homeostatic metaplasticity operates in the human somatosensory cortex, controlling both cortical excitability and somatosensory skill.     

Touch perception threshold in human glabrous skin in terms of displacement amplitude on stimulation with single mechanical pulses

The threshold amplitude for tactile sensation was measured on the finger pads of normal adults using half cycle sinusoidal mechanical pulses. The threshold was about 5 μm for pulses producing rapid skin displacements. With slow pulse stimulation, a sharp rise in threshold to above 80 μm was recorded at a displacement rate of about 0.1 mm/sec. The threshold gap (difference limen) was a fraction of the threshold, on average 27%.The low threshold for rapid pulses is most probably mediated by pacinian corpuscles. The threshold rise on slow pulse stimulation indicates a transfer of the sensation to another type of units which may be the slowly adapting type I.