Hagen Vogel

Inward currents in primary nociceptive neurons of the rat and pain sensations in humans elicited by infrared diode laser pulses.

&NA; Radiant heat is often used to study nociception in vivo. We now used infrared radiation generated by a diode laser stimulator (wavelength 980 nm) to investigate transduction mechanisms for noxious heat stimuli in acutely dissociated dorsal root ganglion (DRG) neurons of rats in vitro. The laser stimulator offered the unique opportunity to test whether the same stimuli also elicit pain sensations in humans. A specific heat‐induced current (Iheat) was elicited in six of 13 small DRG neurons (diameter ≤30 &mgr;m) tested in the whole‐cell configuration of the patch–clamp mode. Current responses in the seven heat‐insensitive neurons were within the range explainable by the temperature dependence of the recording setup. Iheat was characterized by: (1) non‐linearity of its amplitude during a suprathreshold heat ramp as well as with stimuli of increasing intensity with an estimated threshold of 42±1°C; (2) fast rise time and even faster decay time (t1/2=96.5±5.9 and 27.7±1.5 ms, respectively); and (3) rate dependence of its induction. All three heat‐sensitive neurons tested were also sensitive to capsaicin. The mean threshold for the induction of Iheat was 2.8±0.3 J mm−2. The threshold for the induction of action potentials by depolarizing current pulses was significantly reduced after laser stimulation, suggesting a sensitization at the transformation stage. No such change was seen in heat‐insensitive neurons that underwent the same heat stimuli. The same diode laser elicited pain sensations and laser‐evoked potentials in human subjects. No significant differences were seen between the pain thresholds in hairy and in glabrous skin, probably due to the deep penetration of this laser radiation. The mean pain threshold for stimuli ≥200 ms in humans was 2.5±0.2 J mm−2 (n=11), and did not differ from the thresholds for the induction of Iheat in vitro. Our results indicate that Iheat in primary sensory neurons can be activated by infrared laser pulses that are painful in humans.

Brain electrical source analysis of primary cortical components of the tibial nerve somatosensory evoked potential using regional sources

Tibial nerve somatosensory evoked potentials (SEPs) show higher amplitudes ipsilateral to the side of stimulation, whereas subdural recordings revealed a source in the foot area of the contralateral hemisphere. We now investigated this paradoxical lateralization by performing a brain electrical source analysis in the P40 time window (34-46 ms). The tibial nerve was stimulated behind the ankle (8 subjects). On each side, 2048 stimuli were applied twice. SEPs were recorded using 32 magnetic resonance imaging (MRI)-verified electrode positions (bandpass 0.5-500 Hz). In each case, the P40 amplitude was higher ipsilaterally (0.45 +/- 0.14 microV) than contralaterally (-0.49 +/- 0.16 microV). The best fitting regional source, however, was always located in the contralateral hemisphere with a mean distance of 8.2 +/- 4.3 mm from the midline. The positivity pointed ipsilaterally shifting from a frontal orientation (P37) to a parietal direction (P40). The P40 dipole moment was 2.5 times stronger than the dipole moment of P37, which makes P40 most prominent in EEG recordings. However, with its oblique dipole orientation compared to the tangential P37 dipole, it is systematically underestimated in MEG. Dipole orientations explained interindividual variability of scalp potential distribution. SEP amplitudes were smaller when generated in the dominant (left) hemisphere. This is explained by deeper located sources (5.4 +/- 1.6 mm) with a more tangential orientation (delta theta = 17.5 +/- 2.3 degrees) in the left hemisphere.

Attention to pain is processed at multiple cortical sites in man

Painful cutaneous laser stimuli evoked potentials (LEPs) were recorded over the primary somatosensory (SI), parasylvian, and medial frontal (MF) cortex areas in a patient with subdural electrode grids located over these areas for surgical treatment of epilepsy. The amplitudes of the negative (N2*) and positive (P2**) LEP peaks over SI, parasylvian, and MF cortex were enhanced by attention to (counting stimuli), in comparison with distraction from the stimulus (reading for comprehension). Late positive deflections following the P2** peak (late potential—LP) were recorded over MF and from the lateral premotor regions during attention but not during distraction. These findings suggest that attention gates both early (N2*) and late (P2**) pain-related input to SI, parasylvian, and MF cortical regions while the later components (LP) are specifically related to attention.

European vestibular experiments on the Spacelab-1 mission: 7. Ocular counterrolling measurements pre- and post-flight.

SummaryThe static ocular counterrolling (OCR) of the four scientific crew members in the first Spacelab mission was measured during baseline-data-collection before and after the flight of SL-1. It was presumed that the modification of otolithic responses during spaceflight will be reflected in specific changes of the OCR-gain on the first days after recovery. The magnitude of OCR was determined analysing colour-transparencies of subjects right eyes that were produced in different positions of lateral body tilt. In general, one subject did not show any changes at all; three subjects exhibited a significant decrease of OCR-gain after exposure to weightlessness, whereby differences could be found between the responses for small and large angles of lateral body tilt. Moreover, asymmetrical effects of OCR-gain were found between body tilt to the left and tilt to the right side. Two subjects already demonstrated such an asymmetry before the flight with the higher gain on left-tilt (or right eye up), and three subjects exhibited left-right asymmetries after the spaceflight with the higher gain tilting to the right (or right eye down). A possible correlation between these vestibular asymmetries and space-sickness susceptibility is discussed.

European vestibular experiments on the Spacelab-1 mission: 4. Thresholds of perception of whole-body linear oscillation

SummaryThresholds for the detection of linear oscillatory motion at 0.3 Hz in the X, Y and Z body axes were determined during the flight of Spacelab-1 and on the ground pre- and post-flight, using the method of limits with a single staircase procedure. Pre-flight, Z axis thresholds (mean 0.077 ms−2) were significantly higher than X and Y thresholds (mean 0.029 ms−2). Measures obtained on three crew members in-flight exhibited thresholds greater, by a factor of 1.5–4.3, than those obtained pre-flight. Post-flight, two crew members had significantly elevated X and Y axis thresholds whereas the other two crew members had lowered thresholds in X, Y and Z axes. In general, thresholds had returned to pre-flight levels by the second post-flight day. A possible explanation for these somewhat disparate responses is presented.

Dipole source analyses of laser evoked potentials obtained from subdural grid recordings from primary somatic sensory cortex

The cortical potentials evoked by cutaneous application of a laser stimulus (laser evoked potentials, LEP) often include potentials in the primary somatic sensory cortex (S1), which may be located within the subdivisions of S1 including Brodmann areas 3A, 3B, 1, and 2. The precise location of the LEP generator may clarify the pattern of activation of human S1 by painful stimuli. We now test the hypothesis that the generators of the LEP are located in human Brodmann area 1 or 3A within S1. Local field potential (LFP) source analysis of the LEP was obtained from subdural grids over sensorimotor cortex in two patients undergoing epilepsy surgery. The relationship of LEP dipoles was compared with dipoles for somatic sensory potentials evoked by median nerve stimulation (SEP) and recorded in area 3B (see Baumgärtner U, Vogel H, Ohara S, Treede RD, Lenz FA. J Neurophysiol 104: 3029-3041, 2010). Both patients had an early radial dipole in S1. The LEP dipole was located medial, anterior, and deep to the SEP dipole, which suggests a nociceptive dipole in area 3A. One patient had a later tangential dipole with positivity posterior, which is opposite to the orientation of the SEP dipole in area 3B. The reversal of orientations between modalities is consistent with the cortical surface negative orientation resulting from superficial termination of thalamocortical neurons that receive inputs from the spinothalamic tract. Therefore, the present results suggest that the LEP may result in a radial dipole consistent with a generator in area 3A and a putative later tangential generator in area 3B.

Dipole Source Analyses of Early Median Nerve SEP Components Obtained From Subdural Grid Recordings

The median nerve N20 and P22 SEP components constitute the initial response of the primary somatosensory cortex to somatosensory stimulation of the upper extremity. Knowledge of the underlying generators is important both for basic understanding of the initial sequence of cortical activation and to identify landmarks for eloquent areas to spare in resection planning of cortex in epilepsy surgery. We now set out to localize the N20 and P22 using subdural grid recording with special emphasis on the question of the origin of P22: Brodmann area 4 versus area 1. Electroencephalographic dipole source analysis of the N20 and P22 responses obtained from subdural grids over the primary somatosensory cortex after median nerve stimulation was performed in four patients undergoing epilepsy surgery. Based on anatomical landmarks, equivalent current dipoles of N20 and P22 were localized posterior to (n = 2) or on the central sulcus (n = 2). In three patients, the P22 dipole was located posterior to the N20 dipole, whereas in one patient, the P22 dipole was located on the same coordinate in anterior-posterior direction. On average, P22 sources were found to be 6.6 mm posterior [and 1 mm more superficial] compared with the N20 sources. These data strongly suggest a postcentral origin of the P22 SEP component in Brodmann area 1 and render a major precentral contribution to the earliest stages of processing from the primary motor cortex less likely.

European vestibular experiments on the Spacelab-1 mission: 2. Experimental equipment and methods

SummaryA series of vestibular experiments were performed in conjunction with the first Spacelab mission, consisting of sets of pre-, in- and postflight tests. A multipurpose experimental apparatus used for the diverse flight and ground tests is presented. Additional apparatus together with the multi-purpose package were used in the baseline data collection facility at the landing site at NASA Dryden Flight Research Facility for the ground tests. The tests involved optokinetic, caloric and mechanical (whole-body or head-alone) stimulation. The latter included linear acceleration in the subjects x, y and z axes, static roll and yaw about an earth-vertical axis. Physiological parameters such as electro-oculogram (EOG), blood-volume-pulse (BVP), respiration, as well as the stimulus variables such as acceleration and caloric temperature were transmitted to the ground and recorded there. The flight and ground testing schedules are outlined. Problems arising from this complex venture are discussed, and some suggestions are made for future improvement.

The European vestibular experiments in spacelab-1

A series of experiments were performed in the Spacelab-1 mission on November/December, 1983, pre-, in-, and postflight. These experiments covered various aspects of the functions of the vestibular system, the inflight tests comprising threshold measurements for linear movements in three orthogonal axes, optokinetic stimulation, vestibulo-ocular reflexes under linear and angular accelerations, caloric stimulation with and without linear accelerations; pre- and postflight tests repeated the inflight protocol with the addition of subjective vertical and eye counter-rotation measurements using a tilt table. One of the most surprising and significant results was the caloric test: strong caloric nystagmus on the two subjects tested was recorded inflight; this was contrary to what was expected from Baranys convection hypothesis for caloric nystagmus.