Hubert Poláček

Functional magnetic resonance imaging of cerebral activation during spinal cord stimulation in failed back surgery syndrome patients

Spinal cord stimulation (SCS) consisting of electrical stimulation of the dorsal spinal cord using epidural electrodes has been shown to relieve chronic neuropathic pain. To analyze the cerebral activation patterns related to SCS, and to evaluate the effects of SCS on the processing of acute experimental pain, we performed functional magnetic resonance imaging (fMRI) on eight patients suffering from failed back surgery syndrome who were also being treated with SCS for severe pain in their legs and lower back. Three types of stimulation were used, each lasting 36s: (i) SCS, (ii) heat pain (HP) applied to the leg affected by neuropathic pain, and (iii) simultaneous HP and SCS.

Short reflex expirations (expiration reflexes) induced by mechanical stimulation of the trachea in anesthetized cats.

Fifty spontaneously breathing pentobarbital-anesthetized cats were used to determine the incidence rate and parameters of short reflex expirations induced by mechanical stimulation of the tracheal mucosa (ERt). The mechanical stimuli evoked coughs; in addition, 67.6% of the stimulation trials began with ERt. The expiration reflex mechanically induced from the glottis (ERg) was also analyzed (99.5% incidence, p < 0.001 compared to the incidence of ERt). We found that the amplitudes of abdominal, laryngeal abductor posterior cricoarytenoid, and laryngeal adductor thyroarytenoid electromyograms (EMG) were significantly enhanced in ERg relative to ERt. Peak intrathoracic pressure (esophageal or intra-pleural pressure) was higher during ERg than ERt. The interval between the peak in EMG activity of the posterior cricoarytenoid muscle and that of the EMG of abdominal muscles was lower in ERt compared to ERg. The duration of thyroarytenoid EMG activity associated with ERt was shorter than that in ERg. All other temporal features of the pattern of abdominal, posterior cricoarytenoid, and thyroarytenoid muscles EMGs were equivalent in ERt and ERg.In an additional 8 cats, the effect of codeine administered via the vertebral artery was tested. Codeine, in a dose (0.03 mg/kg) that markedly suppressed cough did not significantly alter either the incidence rate or magnitudes of ERt.In the anesthetized cat the ERt induced by mechanical stimulation of the trachea was similar to the ERg from the glottis. These two reflex responses differ substantially only in the frequency of occurrence in response to mechanical stimulus and in the intensity of motor output.

EEG source analysis and fMRI reveal two electrical sources in the fronto-parietal operculum during subepidermal finger stimulation

Using functional magnetic resonance imaging (fMRI) and electroencephalographic (EEG) source dipole analysis in 10 normal subjects, two electrical source dipoles in the contralateral fronto-parietal operculum were identified during repetitive painful subepidermal stimulation of the right index finger. The anterior source dipole peaking at 79 +/- 8 ms (mean +/- SD) was located in the frontal operculum, and oriented tangentially toward the cortical surface. The posterior source dipole peaking at 118 +/- 12 ms was located in the upper bank of the Sylvian fissure corresponding to the second somatosensory cortex (S2). The orientations of the posterior source dipoles displayed large variability, but differed significantly (P < 0.05) from the orientations of the anterior source dipoles. Electrical sources and fMRI clusters were also observed in ipsilateral fronto-parietal operculum. However, due to low signal-to-noise ratio of ipsilateral EEG sources in individual recordings, separation of sources into anterior and posterior clusters was not performed. Combined fMRI and source dipole EEG analysis of individual data suggests the presence of two distinct electrical sources in the fronto-parietal operculum participating in processing of somatosensory stimuli. The anterior region of the fronto-parietal operculum shows earlier peak activation than the posterior region.

Effects of spinal cord stimulation on the cortical somatosensory evoked potentials in failed back surgery syndrome patients

OBJECTIVE To evaluate the functional activation of the somatosensory cortical regions in neuropathic pain patients during therapeutic spinal cord stimulation (SCS). METHODS In nine failed back surgery syndrome patients, the left tibial and the left sural nerves were stimulated in two sessions with intensities at motor and pain thresholds, respectively. The cortical somatosensory evoked potentials were analyzed using source dipole analysis based on 111 EEG signals. RESULTS The short-latency components of the source located in the right primary somatosensory cortex (SI: 43, 54 and 65ms) after tibial nerve stimulation, the mid-latency SI component (87ms) after sural nerve stimulation, and the mid-latency components in the right (approximately 161ms) and left (approximately 168ms) secondary somatosensory cortices (SII) were smaller in the presence of SCS than in absence of SCS. The long-latency source component arising from the mid-cingulate cortex (approximately 313ms) was smaller for tibial and larger for sural nerve stimuli during SCS periods compared to periods without SCS. CONCLUSIONS SCS attenuates the somatosensory processing in the SI and SII. In the mid-cingulate cortex, the effect of SCS depends on the type of stimulation and nerve fibers involved. SIGNIFICANCE Results suggest that the effects of SCS on cortical somatosensory processing may contribute to a reduction of allodynia during SCS.

Source imaging of the cortical 10 Hz oscillations during cooling and warming in humans.

Primary cold and warm afferent fibers show a robust overshoot in their firing during periods of temperature change, which subsides during tonic thermal stimulation. Our objective was to analyze cortical activation, on a scale of hundreds of milliseconds, occurring during the process of dynamic cooling and warming, based on an evaluation of the amplitude changes seen in 10 Hz electroencephalographic oscillations. Eleven right-handed subjects were exposed to innocuous cold ramp stimuli (from 32 degrees C to 22 degrees C, 10 degrees C/s) and warm ramp stimuli (32 degrees C to 42 degrees C, 10 degrees C/s) on the thenar region of their right palm, using a contact thermode. EEG was recorded from 111 scalp sites, and the 10 Hz current source densities were modeled using low-resolution electromagnetic tomography. During cooling, the earliest amplitude decreases of 10 Hz oscillations were seen in the contralateral posterior insula and secondary somatosensory cortex (SII), and the premotor cortex (PMC). During warming, the earliest events were only observed in the PMC and occurred approximately 0.7 s later than during cooling. Linear regression analysis between 10 Hz current source densities and temperature variations revealed cooling-sensitive activation in the bilateral posterior insula, PMC and the anterior cingulate cortex. During warming, the amplitude of 10 Hz oscillations in the PMC and posterior insula correlated with stimulus temperature. Dynamic thermal stimulation activates, in addition to the posterior insula and parietal operculum, the lateral PMC. The activation of the anterior cingulate cortex during cooling may aid in the anticipation of the cold temperature end-point and provide continuous evaluation of the thermal stimulus.

Cortical oscillatory changes during warming and heating in humans.

Warmth and heat are registered by different types of cutaneous receptors. To disentangle the cortical activation patterns of warming and heating, we analyzed the temporal evolution of the electroencephalographic 10 and 20 Hz oscillations with the time resolution of hundreds of milliseconds. Sixty heat (from 32 to 50.5 degrees C, rate of change 6 degrees C/s) and warm (from 32 to 42 degrees C, 6 degrees C/s) stimuli were applied on the right thenar using contact thermode. EEG was recorded from 111 scalp electrodes in 12 healthy subjects, and analyzed using event-related desynchronization and low-resolution electromagnetic tomography methods. During warming, the amplitudes of 10 and 20 Hz oscillations over the contralateral primary sensorimotor (SI/MI) and premotor cortices decreased, and the amplitude of 20 Hz oscillations in the anterior cingulate and ipsilateral premotor cortex increased. Heating was associated with additional profound amplitude decreases of 10 and 20 Hz oscillations over SI/MI and premotor cortex, and by amplitude increase of 20 Hz oscillations originating in the posterior cingulate cortex. Results suggest biphasic amplitude changes of the cortical oscillations during ramp increase of temperature attributable to the periods of warming and heating. The amplitude decreases of 10 and 20 Hz oscillations in SI/MI and premotor cortex possibly aid in preparation of motor withdrawal reaction in an event that temperature should reach intolerable pain. Synchronization of the 20 Hz oscillations in the anterior and especially in the posterior cingulate cortex may aid suppression of unwanted movements.

Somatosensory-evoked potentials are influenced differently by isometric muscle contraction of stimulated and non-stimulated hand in humans

Chronic pain is associated with motor dysfunctions, and stimulation of the motor cortex has been shown to alleviate chronic pain. Recently Nakata et al. [Pain 107 (2004) 91-98] showed differentiated patterns of neuromagnetic evoked fields following painful laser stimulation during phasic movements of stimulated and non-stimulated hand. Phasic movements and static contractions differ in their functional activation of the motor cortices. Therefore, we decided to analyze the effects of isometric contractions of intrinsic right and left hand muscles on cortical sources of somatic-evoked potentials related to a painful galvanic stimulation of the right middle finger. Using spatio-temporal source dipole analysis of 111 electroencephalographic signals in 10 right-handed men, source activities were evaluated in the left primary somatosensory cortex (S1), left (S2(L)) and right (S2(R)) secondary somatosensory cortex, anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC). Ipsilateral hand muscle contraction was associated with a decrease of source activity in S1 and with subsequent increases in S2(L) and the PCC. Contralateral hand muscle contraction was accompanied by a decrease of source activity in bilateral S2 cortices followed by decreases in the S1 and anterior cingulate cortex. Results suggest early suppression of source activity in S1 during ipsilateral hand muscle contractions and in bilateral S2 during contralateral hand muscle contractions.

A novel JAK2 exon 12 mutation identified in the retrospective analysis of paraffin-embedded tissues of polycythemia vera patients.

The aim of the study was to screen formalin-fixed, paraffin-embedded tissues of polycythemia vera patients for the presence of JAK2V617F and JAK2 exon 12 mutations. Of 64 cases, 60 were positive for JAK2V617F mutation using allele-specific polymerase chain reaction (PCR). Using modified allele-specific PCR, samples of 4 JAK2V617F-negative patients were analyzed for the presence of JAK2 exon 12 mutations. In one case, we found a PCR product matching with allele-specific primer, which was designed to detect the N542-E543del mutation. Surprisingly, in the result sequence we have detected another recently described mutation, R541-E543delinsK. In the other 3 JAK2V617F-negative patients, allele-specific PCR for the detection of JAK2 exon 12 mutations did not yield any product. However, in 1 case, the sequencing of JAK2 exon 12 PCR product revealed a novel mutation, H538-K539delinsF. We confirmed that paraffin-embedded tissues represent a valuable source of DNA, which can be used in diagnostics of both JAK2 exon 12 and exon 14 mutations and we described 1 novel JAK2 exon 12 mutation.

Bursts of 15-30 Hz oscillations following noxious laser stimulus originate in posterior cingulate cortex.

Previous EEG studies reported the presence of synchronised 15-30 Hz oscillations in vertex electrodes following innocuous somatosensory stimulation and noxious laser stimulation. The purpose of the present study was to analyse the sources of poststimulus increases of 15-30 Hz oscillations during noxious laser stimulation of four different body regions and to compare the sources of the poststimulus synchronisation with the sources of the N2 component of laser-evoked potential (LEP). In 10 healthy subjects, moderately painful laser stimuli were applied to the dorsum of the right hand, dorsum of the right foot, right groin, and right side of the face. EEG data, recorded from 111 scalp sites, were analysed using event-related desynchronisation method and source dipole analysis. A profound amplitude increase of 15-30 Hz oscillations peaking 1-2 s after noxious laser stimulation was found during stimulation of each body part. The sources of these oscillations were located in the dorsal posterior cingulate cortex and showed no somatotopic arrangement. The sources of the N2-LEP component were located in the anterior mid-cingulate cortex 25-30 mm rostral to the sources of 15-30 Hz oscillations. The amplitude of the poststimulus synchronisation of 15-30 Hz oscillations correlated (P<0.05) with the amplitude of N2-LEP component. Results show that noxious laser stimuli induce bursts of 15-30 Hz oscillations in the posterior cingulate cortex. The poststimulus increases of 15-30 Hz oscillations may stand for transient cortical inhibition possibly aiding temporary suppression of motor programs that have been primed by noxious stimulation.

Hypothalamic damage in multiple sclerosis correlates with disease activity, disability, depression, and fatigue

Abstract Objectives: Disturbances in the hypothalamo-pituitary axis are supposed to modulate activity of multiple sclerosis (MS). We hypothesised that the extent of HYP damage may determine severity of MS and may be associated with the disease evolution. We suggested fatigue and depression may depend on the degree of damage of the area. Method: 33 MS patients with relapsing-remitting and secondary progressive disease, and 24 age and sex-related healthy individuals (CON) underwent 1H-MR spectroscopy (1H-MRS) of the hypothalamus. Concentrations of glutamate + glutamin (Glx), cholin (Cho), myoinositol (mIns), N-acetyl aspartate (NAA) expressed as ratio with creatine (Cr) and NAA were correlated with markers of disease activity (RIO score), Multiple Sclerosis Severity Scale (MSSS), Depressive-Severity Status Scale and Simple Numerical Fatigue Scale. Results: Cho/Cr and NAA/Cr ratios were decreased and Glx/NAA ratio increased in MS patients vs CON. Glx/NAA, Glx/Cr, and mIns/NAA were significantly higher in active (RIO 1–2) vs non-active MS patients (RIO 0). Glx/NAA and Glx/Cr correlated with MSSS and fatigue score, and Glx/Cr with depressive score of MS patients. In CON, relationships between Glx/Cr and age, and Glx/NAA and fatigue score were inverse. Conclusion: Our study provides the first evidence about significant hypothalamic alterations correlating with clinical outcomes of MS, using 1H-MRS. The combination of increased Glu or mIns with reduced NAA in HYP reflects whole-brain activity of MS. In addition, excess of Glu is linked to severe disease course, depressive mood and fatigue in MS patients, suggesting superiority of Glu over other metabolites in determining MS burden.