M. Valeriani

Cortical changes to experimental sensitization of the human esophagus

Topographical organization in the neocortex shows experience-dependent plasticity. We hypothesized that experimental sensitization of the esophagus results in changes of the topographical distribution of the evoked potentials and the corresponding dipole source activities to painful stimulation. An endoscopic method was used to deliver 35 electrical stimuli at the pain threshold to a fixed area of the mucosa in 10 healthy volunteer men and women. The stimulations were repeated after 30 min (reproducibility experiment), and after 60 min following perfusion of 200 ml 0.1 N hydrochloric acid (sensitization experiment). During stimulation the electroencephalogram was recorded from 64 surface electrodes. The sensitization resulted in a decrease in the pain threshold (F=6.2; P=0.004). The topographic distribution of the evoked potentials showed reproducible negative (N1, N2) and positive (P1, P2) components. After acid perfusion a reduced latency and a change in localization was seen for the P1 subdivided into frontal and occipital components (F=29.5, P<0.001; F=53.7, P<0.001). Furthermore the sensitization resulted in a reduction of the latency for P2 (F=6.2, P=0.009). The source analysis showed consistent dipolar activity in the bilateral opercular-insular cortex before and after acid perfusion. For the anterior cingulate dipole there was a reduction in latency (P=0.03) and a posterior shift (P=0.0002) following acid perfusion. The findings indicate that short-term sensitization of the esophagus results in central neuroplastic changes involving the cingulate gyrus, which also showed pathological activation in functional diseases of the gut, thus reflecting the importance of this region in visceral pain and hyperalgesia.

Segmental dysfunction of the cervical cord revealed by abnormalities of the spinal N13 potential in cervical spondylotic myelopathy

We studied somatosensory potentials (SEPs) evoked by stimulation of radial, median, and ulnar nerves in 11 patients with MRI evidence of cervical spondylosis. All patients presented with progressive spastic paraparesis that was either isolated or associated with lower motor neuron signs in the upper limbs, with preserved joint, touch, pain, and temperature sensations in the four limbs. In all patients, scalp SEPs reflecting tho activity of the dorsal column system up to the parietal cortex were normal while segmental cervical cord dysfunction was manifested by an abnormal spinal N13 potential in 95% of radial, 90% of median, and 54% of ulnar nerve SEPs. These subclinical abnormalities of the spinal N13 SEP probably result from reduced blood supply due to compression of the anterior spinal artery in patients with cervical spondylotic myelopathy.

Cervical cord dysfunction during neck flexion in Hirayama’s disease

Neck flexion may play a role in the pathogenesis of Hirayama disease. Upper limb somatosensory evoked potentials were recorded in five patients with Hirayama disease, six patients with ALS, and 14 healthy subjects. Neck flexion caused a significant amplitude decrease of the N13 cervical response only in patients with Hirayama disease. Direct cord compression or microvascular changes can in theory account for this position-related dysfunction.

Cerebral processing of painful oesophageal stimulation: a study based on independent component analysis of the EEG

Background and aims: Independent component analysis (ICA) of the electroencephalogram (EEG) overcomes many of the classical problems in EEG analysis. We used ICA to determine the brain responses to painful stimulation of the oesophagus. Methods: Twelve subjects with a median age of 41 years were included. With a nasal endoscope, two series of 35 electrical stimuli at the pain threshold were given to the distal oesophagus and the EEG was subjected to ICA. The sessions were separated by 30 minutes. For each component head models, event related images, spectral perturbation, coherence analysis, and dipoles were extracted. The most valid components were found according to time/frequency information and reliability in both experiments. Results: Reliable components with the most valid dipoles were found in the thalamus, insula, cingulate gyrus, and sensory cortex. Time locked activities were consistent with upstream activation of these areas, and cross coherence analysis of the sources demonstrated dynamic links in the β(14–25 Hz) and γ(25–50 Hz) bands between the suggested networks of neurones. The thalamic components were time and phase locked intermittently, starting around 50 ms. In the cingulate gyrus, the posterior areas were always firstly activated, followed by the middle and anterior regions. Components with dipoles in the sensory cortex were localised in several regions of the somatosensory area. Conclusions: The method gives new information relating to the localisation and dynamics between neuronal networks in the brain to pain evoked from the human oesophagus, and should be used to increase our understanding of clinical pain.

Short and middle-latency Median Nerve (MN) SEPs recorded by depth electrodes in human pre-SMA and SMA-proper

OBJECTIVE To analyse waveforms, latencies and amplitudes of Median Nerve (MN) SEPs recorded by stereotactically electrodes implanted in the SMA of 14 epileptic patients (9 in pre-SMA,3 in SMA-proper, 2 in both) in order to evaluate which short and middle-latency SEPs are generated in this area and which could be the physiological relevance of these responses. METHODS Short and middle-latency MN SEPs were recorded by chronically implanted electrodes in the fronto-temporal cortex and in particular in the mesial frontal region of 14 drug-resistant epileptic patients. MN stimulations of 100 micros were delivered by skin electrodes at the wrist; stimulus intensity was adjusted slightly above the motor threshold. RESULTS The main result of this study is that middle-latency SEPs were originated in pre-SMA but not in SMA-proper as demonstrated by both referential and bipolar recordings. In particular off-line computed bipolar traces between neighbouring contacts implanted in the pre-SMA and in the frontal external regions showed a phase reversal at the deepest contacts located in pre-SMA. Conversely, bipolar recordings between neighbouring contacts implanted in the SMA-proper and in the frontal external regions showed inversion recovery at more superficial contacts, implanted in area 6. Finally, we confirmed that no short-latency MN SEP (and in particular the N30) is originated in the whole SMA. CONCLUSIONS Among premotor areas, somatosensory inputs seem to reach pre-SMA and area 6 but not SMA-proper. SIGNIFICANCE This study assessed that no scalp SEP in the first 100 ms after MN stimulus could be generated in SMA-proper.

Somatosensory evoked potentials after multisegmental upper limb stimulation in diagnosis of cervical spondylotic myelopathy.

Radial, median, and ulnar nerve somatosensory evoked potentials (SEPs) were recorded, with non-cephalic reference montage, in 38 patients with clinical signs of cervical myelopathy and MRI evidence of spondylotic compression of the cervical cord. Upper limb SEPs are useful in spondylotic myelopathy because SEPs were abnormal in all patients for at least one of the stimulated nerves and SEP abnormalities were bilateral in all patients but one. Reduction of the amplitude of the N13 potential indicating a segmental dysfunction of the cervical cord was the most frequent abnormality; it occurred in 93.4%, 84.2%, and 64.5% of radial, median, and ulnar nerve SEPs respectively. A second finding was that the P14 far-field potential was more sensitive than the cortical N20 potential to slowing of conduction in the dorsal column fibres. The high percentage of N13 abnormalities in the radial and median rather than in the ulnar nerve SEPs correlated well with the radiological compression level, mainly involving the C5-C6 vertebral segments. Therefore the recording of the N13 response is a reliable diagnostic tool in patients with cervical spondylotic myelopathy and P14 abnormalities, though less frequent, can be useful in assessing subclinical dorsal column dysfunction.

Contribution of GABAergic cortical circuitry in shaping somatosensory evoked scalp responses: specific changes after single-dose administration of tiagabine.

OBJECTIVES To determine whether conventional as well as high-frequency somatosensory evoked potentials (SEPs) to upper limb stimulation are influenced by GABAergic intracortical circuitry. METHODS We recorded SEPs from 6 healthy volunteers before and after a single-oral administration of tiagabine. Conventional low-frequency SEPs have been obtained after stimulation of the median nerve, as well as after stimulation of the first phalanx of the thumb, which selectively involves cutaneous finger inputs. Median nerve SEPs have been further analyzed after digital narrow-bandpass filtering, to selectively examine high-frequency responses. Lastly, in order to explain scalp SEP distribution before and after tiagabine administration, we performed the brain electrical source analysis (BESA) of raw data. RESULTS After tiagabine administration, conventional scalp SEPs showed a significant amplitude increase of parietal P24, frontal N24 and central P22 components. Similarly, BESA showed a significant strength increase of the second peak of activation of the first two perirolandic dipoles, which are likely to correspond to the N24/P24 and P22 generators. By contrast, no significant changes of high-frequency SEPs were induced by drug intake. CONCLUSIONS Our findings support the view that both N24/P24 and P22 SEP components are probably generated by deep spiny cell hyperpolarization, which is strongly increased by inhibitory inputs from GABAergic interneurons. By considering the clear influence of inhibitory circuitry in shaping these SEP components, conventional scalp SEP recording could be useful in the functional assessment of the somatosensory cortex in different physiological and pathological conditions. By contrast, intrinsic firing properties of the cell population generating high-frequency SEP responses are unaffected by the increase of recurrent GABAergic inhibition.

Inhibitory effect of voluntary movement preparation on cutaneous heat pain and laser-evoked potentials

In our study, preparation of voluntary movement was used to physiologically activate the motor cortex areas and the effect of this activation on CO2 laser‐evoked potentials (LEPs) was explored. LEPs were recorded from 31 scalp electrodes in 10 healthy subjects after painful stimulation of the right C6–C7 skin dermatomes. LEP stimuli were delivered in the time interval between a visual warning stimulus followed after 1 s. by an imperative stimulus. The imperative stimulus triggered: (i) no task in the baseline condition (Pain); (ii) flexion–extension movements of the second finger of the right hand in the movement condition (Pain + Movement); (iii) cognitive task (mathematic computation) in the distraction condition (Pain + Cognition). The experimental conditions were also repeated during application of laser stimuli on the left C6–C7 skin dermatomes. Compared with the baseline condition (no task required), during preparation of right‐hand voluntary movement there was a significant reduction in LEP amplitude and subjective pain rating after right‐ but not after left‐hand stimulation, which suggests that the observed effect cannot be attributed to a nonspecific reduction in attention toward painful stimulus. During preparation of a cognitive task, LEP amplitude was reduced compared to baseline. Our results represent the first neurophysiological suggestion that physiological activation of the motor cortex, occurring during movement preparation, inhibits cortical pain processing by a centrifugal mechanism.

Segmental inhibition of cutaneous heat sensation and of laser-evoked potentials by experimental muscle pain

The aim of the study was to evaluate the effect of tonic muscle pain evoked by injection of 5% hypertonic saline in the right brachioradialis muscle on the somatosensory sensation of laser-evoked heat pain and laser-evoked potentials. The heat pain pathways were studied in 9 healthy human subjects by recording the scalp potentials evoked by CO(2) laser stimuli delivered on four sites: the skin above the right brachioradialis muscle (ipsilateral local pain), the wrist area where muscle pain was referred in all subjects (ipsilateral referred pain), and two areas on the left arm symmetrical to both local and referred pain (contralateral local pain and contralateral referred pain). Laser-evoked potentials were obtained from 31 scalp electrodes before saline injection, during saline infusion (bolus injection with 0.3 ml saline infused over 20 s, followed by a steady infusion rate of 30 ml/h for the next 25 min), and 20 min after muscle pain had disappeared. While the early N1/P1 component (around 130 ms and 145 ms of latency after stimulation of the skin over the brachioradialis muscle and the wrist, respectively) was not affected by muscle pain, the amplitudes of the later vertex laser-evoked potentials (N2 latency of around 175 ms and 210 ms after stimulation of the skin over the brachioradialis muscle and the wrist, respectively; P2 latency of around 305 ms and 335 ms after stimulation of the skin over the brachioradialis muscle and the wrist, respectively) evoked from ipsilateral local pain, ipsilateral referred pain, and contralateral local pain sites were significantly decreased during muscle pain compared with the baseline recording, while they recovered after pain had disappeared. At the same stimulation sites, the rating of the laser-evoked pain sensation was reduced significantly during muscle pain as compared with the baseline and it recovered after pain had disappeared. On the contrary, muscle pain did not show any effect on both laser-evoked pain and laser-evoked potential amplitude when the contralateral referred pain site was stimulated. The muscle pain inhibitory effect on both heat pain sensation and laser-evoked potential amplitude is probably mediated by an ipsilateral and contralateral segmental mechanism which acts also on the referred pain area, while more general inhibitory mechanisms, such as a distraction effect or a diffuse noxious inhibitory control, are excluded by the absence of any effect of muscle pain on laser-evoked pain and laser-evoked potentials obtained from a remote site, such as the contralateral referred pain area. Since muscle pain induced by hypertonic saline injection is very similar to clinical pain, our results can be useful in understanding the pathophysiology of the somatosensory modifications which can be observed in patients with musculoskeletal pain syndromes.

The human supplementary motor area-proper does not receive direct somatosensory inputs from the periphery: data from stereotactic depth somatosensory evoked potential recordings

Somatosensory evoked potentials to median nerve (MN) stimulation were recorded by stereotactically implanted electrodes in the frontal lobe of two epileptic patients in order to evaluate whether short-latency cortical responses could be generated in the supplementary motor area (SMA)-proper. In both patients two potentials, called P20 and N30 responses, showed a decreasing amplitude from the most superficial to the deepest contacts and were recorded in the white as well in the grey matter of the frontal lobe. Furthermore, no phase reversal of both P20 and N30 potentials was identifiable along electrode trajectories. Our results suggest that short-latency somatosensory evoked responses recorded in the SMA-proper contralateral to MN stimulation are volume conducted from remote cortical generators.