Etoricoxib pre-medication for post-operative pain after laparoscopic cholecystectomy.

BACKGROUND: Etoricoxib alleviates and prevents acute pain. The hypothesis of our study was that the pre-operative use of etoricoxib would reduce the post-operative need for additional pain treatment. METHODS: In this double-blind, randomized and active placebo-controlled study, 75 patients were pre-medicated 1.5 h before elective laparoscopic cholecystectomy with 120 mg of etoricoxib (E120 group), the same dose of etoricoxib combined with 1 g of paracetamol (E + P group) or placebo (Pla group). To alleviate post-operative pain, a patient-controlled analgesia (PCA) device was programmed to deliver 50 microg of fentanyl intravenously (lockout time, 5 min). The pain intensity and nausea were assessed using a visual analogue scale (VAS). The number of patients with post-operative nausea and vomiting was recorded. Blood loss was compared between the groups. Because the operations are almost blood-less, the operation time was also recorded to compare the possible effect on bleeding time. RESULTS: Pre-medication with etoricoxib or etoricoxib plus paracetamol had a statistically significant fentanyl-sparing effect 2-20 h post-operatively compared with placebo (P = 0.001). No significant differences were demonstrated in fentanyl-sparing effect between the E120 and E + P groups. No significant differences in pain intensity were found between the three study groups. No significant differences were observed between the groups with regard to nausea, blood loss, duration of anaesthesia or duration of surgery. CONCLUSION: Etoricoxib is suitable for pre-medication before laparoscopic cholecystectomy as it reduces the need for post-operative opioids. Opioid-related side-effects, however, were not reduced in the present study, despite the observed opioid-sparing effect of etoricoxib and combined etoricoxib and paracetamol.

Neuromagnetic responses to vowels vs. tones reveal hemispheric lateralization.

OBJECTIVE: To evaluate whether a simple auditory paradigm could demonstrate a difference in cortical lateralization between right- and left-handed subjects. Such information would be important for later development of clinical noninvasive tests of hemispheric language dominance in candidates for brain surgery. METHODS: Healthy subjects (10 strongly right-handed, 10 strongly left-handed, 5 weakly right-handed, and two ambidextrous) listened to binaural pairs of tones and pairs of Finnish vowels and decided whether the items in the pair were the same (target probability 20%). Cortical responses were recorded with whole-scalp magnetoencephalography. RESULTS: The laterality index for strengths of the auditory-cortex 100 ms responses (N100m) to vowels vs. tones suggested left-hemispheric dominance in 8 of the 10 strongly right-handed subjects, and right-hemispheric dominance in 7 of the 10 left-handed subjects. CONCLUSIONS: Our results demonstrate difference in hemispheric dominance for processing of vowels between right-handed and left-handed subjects. This difference resembles language lateralization suggested by previous invasive studies as well as by anatomical and functional comparisons in left- and right-handed subjects. SIGNIFICANCE: After comparison with the Wada test, this simple paradigm could prove useful as a noninvasive test for language lateralization in clinical settings.

Neuromagnetic localization of rhythmic activity in the human brain: a comparison of three methods.

Cortical rhythmic activity is increasingly employed for characterizing human brain function. Using MEG, it is possible to localize the generators of these rhythms. Traditionally, the source locations have been estimated using sequential dipole modeling. Recently, two new methods for localizing rhythmic activity have been developed, Dynamic Imaging of Coherent Sources (DICS) and Frequency-Domain Minimum Current Estimation (MCE(FD)). With new analysis methods emerging, the researcher faces the problem of choosing an appropriate strategy. The aim of this study was to compare the performance and reliability of these three methods. The evaluation was performed using measured data from four healthy subjects, as well as with simulations of rhythmic activity. We found that the methods gave comparable results, and that all three approaches localized the principal sources of oscillatory activity very well. Dipole modeling is a very powerful tool once appropriate subsets of sensors have been selected. MCE(FD) provides simultaneous localization of sources and was found to give a good overview of the data. With DICS, it was possible to separate close-by sources that were not retrieved by the other two methods.

Left-hemisphere dominance for processing of vowels: a whole-scalp neuromagnetic study.

Brain activation of 11 healthy right-handed subjects was studied with magnetoencephalography to estimate individual hemispheric dominance for speech sounds. The auditory stimuli comprised binaurally presented Finnish vowels, tones, and piano notes in groups of two or four stimuli. The subjects were required to detect whether the first and the last item in a group were the same. In the left hemisphere, vowels evoked significantly stronger (37-79%) responses than notes and tones, whereas in the right hemisphere the responses to different stimuli did not differ significantly. Specifically, in the two-stimulus task, all 11 subjects showed left-hemisphere dominance in the vowel vs tone comparison. This simple paradigm may be helpful in non-invasive evaluation of language lateralization.

Subject's own speech reduces reactivity of the human auditory cortex.

Previous studies on monkeys have shown that uttering-related cortical areas exert an inhibitory effect on the auditory cortex, and cerebral blood-flow analyses on humans have revealed modulation of the activity of the auditory cortex during own speech. To study this modulation on a millisecond time scale, we recorded neuromagnetic evoked responses to short 1-kHz tones while the subjects were reading silently and aloud. The 100-ms response (M100) of the auditory cortex was delayed by 10-21 ms and its amplitude was dampened by 44-71% during reading aloud compared with reading silently. This effect was more prominent in responses to ipsilateral than contralateral tones, possibly due to a sum effect of diminished ipsilateral input to the cortex and decreased transcallosal excitation.

An MEG study of picture naming.

The purpose of this study was to relate a psycholinguistic processing model of picture naming to the dynamics of cortical activation during picture naming. The activation was recorded from eight Dutch subjects with a whole-head neuromagnetometer. The processing model, based on extensive naming latency studies, is a stage model. In preparing a picture"s name, the speaker performs a chain of specific operations. They are, in this order, computing the visual percept, activating an appropriate lexical concept, selecting the target word from the mental lexicon, phonological encoding, phonetic encoding, and initiation of articulation. The time windows for each of these operations are reasonably well known and could be related to the peak activity of dipole sources in the individual magnetic response patterns. The analyses showed a clear progression over these time windows from early occipital activation, via parietal and temporal to frontal activation. The major specific findings were that (1) a region in the left posterior temporal lobe, agreeing with the location of Wernicke"s area, showed prominent activation starting about 200 msec after picture onset and peaking at about 350 msec (i.e., within the stage of phonological encoding), and (2) a consistent activation was found in the right parietal cortex, peaking at about 230 msec after picture onset, thus preceding and partly overlapping with the left temporal response. An interpretation in terms of the management of visual attention is proposed.

Neuromagnetic sequelae of herpes simplex encephalitis.

Spontaneous cortical activity and auditory evoked responses were recorded with a whole-scalp 122-channel neuromagnetometer from 4 patients after left-hemisphere dominant herpes simplex encephalitis and associated memory disorders. Spontaneous activity of one patient contained periodic sharp waves over the left hemisphere; the background activity was attenuated. The sources of periodic sharp waves clustered close to the sources of auditory evoked fields in the temporal lobe. In controls, dominant rhythmic activity over the parieto-occipital region had spectral maximum at 10.6 +/- 0.6 Hz; in patients the dominant rhythmic activity peaked at 8.6 +/- 1.8 Hz. The suppression of the parieto-occipital activity in eyes-open versus eyes-closed condition was smaller in patients than in controls. The patients' peak spectral frequency was correlated with neuropsychological tests reflecting deficient attentional capacity. The observed changes probably reflect decreased subcortical control of the cortical electric activity.

Functional organization of the auditory cortex is different in stutterers and fluent speakers.

Impaired auditory feedback has been suggested to cause stuttering, and subtle irregularities of audition have been reported in behavioural studies. To characterize processing at the auditory cortical level, we recorded neuromagnetic responses to monaural tones in nine stutterers and 10 fluent speakers while the subjects were reading silently, with mouth movements only, aloud, and in chorus with another person. The basic functional organization of the auditory cortices was found to be different in stutterers and controls. The altered interhemispheric balance in stutterers was affected by speech production, due to changes in the left auditory cortical representation, and more severely by self-paced than accompanied speech. This may lead to transient non-optimal interpretation of the auditory input and affect speech fluency.

Modification of neuromagnetic cortical signals by thalamic infarctions.

Auditory evoked responses and spontaneous cortical activity were recorded with a whole-scalp 122-channel neuromagnetometer from 7 patients, who had small thalamic infarctions in the region of the left anterior tuberothalamic artery and associated memory defects. In contrast to healthy control subjects, with dominant rhythmic activity at 10.6 +/- 0.6 Hz in the parieto-occipital region, the spectral maximum in the patients was at 8.9 +/- 0.4 Hz. Abnormal acceleration of rhythmic activity was also observed bilaterally in rolandic areas. Our findings imply that lesions of non-specific thalamic nuclei may disturb human brain rhythms in widespread cortical areas. 'Mismatch responses' to deviant tones (1.1 kHz) among standards (1.0 kHz), suggested to reflect sensory auditory memory in healthy subjects, were absent in 2 patients, markedly decreased in 3, and normal in 2, implying that pathways passing through the anteromedial thalamus contribute to modulation of these responses. We conclude that local unilateral lesions in the anteromedial thalamus may cause extensive, bilateral alterations in the brain's electric activity.

Global optimization in the localization of neuromagnetic sources.

The locations of active brain areas can be estimated from the magnetic field produced by the neural current sources. In many cases, the actual current distribution can be modeled with a set of stationary current dipoles with time-varying amplitudes. This work studies global optimization methods that find the minimum of the least-squares error function of the current dipole estimation problem. Three different global optimization methods were investigated: clustering method, simulated annealing, and genetic algorithms. In simulation studies, the genetic algorithm was the most effective method. The methods were also applied to analysis of actual measurement data.

Activation of the human occipital and parietal cortex by pattern and luminance stimuli: neuromagnetic measurements.

We compared cortical reactivity to pattern and luminance stimuli by recording evoked responses and spontaneous brain rhythms from 10 subjects with a whole-scalp neuromagnetometer. Hemifield patterns (black-and-white checkerboards) elicited strong contralateral transient activation of the occipital V1/V2 cortex, maximum at 65-75 ms, followed by sustained activation during the 2 s stimulus. Responses to hemifield luminance stimuli also had an occipital component, but they were dominated by activation of the medial parieto-occipital sulcus (POS) 60-70 ms later. The POS region was equally well activated by foveal and extrafoveal stimuli. The occipital responses to hemifield luminance stimuli differed from those to pattern stimuli in two main aspects: the sustained activation was significantly weaker, and the responses were almost symmetrical, indicating a surprisingly bilateral occipital activation. These effects were similar with foveal and extrafoveal stimuli. The spontaneous 10 Hz alpha rhythm, originating predominantly in the POS region, was suppressed after both stimulus onsets and offsets, more strongly for luminance than pattern stimuli. Activation of the occipital cortex dominated after pattern stimuli, whereas the effect of luminance stimulation was stronger in the parieto-occipital region. The distinct signal distributions in the occipital and POS regions suggest that the two types of stimuli activate the magno- and parvocellular pathways to a varying degree. These findings are also in line with a stronger attention-catching value of the luminance than pattern stimuli.

Responsiveness of human cortical activity to rhythmical stimulation: a three-modality, whole-cortex neuromagnetic investigation.

We developed numerical indicators to quantify stimulus-related changes in cortical magnetic signals recorded from nine healthy subjects while they received 1- to 2.5-s trains of 15 stimuli (somatosensory, visual, or auditory in separate runs) at rates from 6 to 14 Hz, intermingled with 1.6-s pauses. A locking index (L) was introduced to quantify how well the responses are time locked to the stimuli and a global change factor (GC) to indicate changes in the whole-cortex oscillatory activity in the 5- to 25-Hz frequency range. The responses were visualized with color-coded images illustrating cortical reactivity for all stimulus rates simultaneously. These color maps clearly showed that the modality-specific cortical signals were enhanced at frequencies corresponding to the stimulus rate during the trains. For somatosensory stimulation the activity in the vicinity of the somatosensory hand area was enhanced at most stimulus rates, suggesting mainly superposition of evoked responses. In individuals with strong posterior resting rhythm, visual stimuli typically entrained activity in the parietooccipital sulcus at stimulus rates close to the main frequency of the spontaneous activity, probably reflecting driving of the intrinsic cortical rhythm, whereas in subjects with little spontaneous parietooccipital rhythm the cortical signal appeared to be composed mainly of visual evoked responses. No modality-specific enhancement was observed during auditory stimulation. During the pauses between the trains, the cortical signals were significantly suppressed compared with the resting condition: The peak activity (7-13 Hz) was modulated within, but also outside, the modality-specific areas, and the signals outside the frequency peaks of maximum power were consistently and reproducibly suppressed over the whole cortex by all stimuli.

Involvement of primary motor cortex in motor imagery: a neuromagnetic study.

Functional brain imaging studies have indicated that several cortical and subcortical areas active during actual motor performance are also active during imagination or mental rehearsal of movements. Recent evidence shows that the primary motor cortex may also be involved in motor imagery. Using whole-scalp magnetoencephalography, we monitored spontaneous and evoked activity of the somatomotor cortex after right median nerve stimuli in seven healthy right-handed subjects while they kinesthetically imagined or actually executed continuous finger movements. Manipulatory finger movements abolished the poststimulus 20-Hz activity of the motor cortex and markedly affected the somatosensory evoked response. Imagination of manipulatory finger movements attenuated the 20-Hz activity by 27% with respect to the rest level but had no effect on the somatosensory response. Slight constant stretching of the fingers suppressed the 20-Hz activity less than motor imagery. The smallest possible, kinesthetically just perceivable finger movements resulted in slightly stronger attenuation of 20-Hz activity than motor imagery did. The effects were observed in both hemispheres but predominantly contralateral to the performing hand. The attempt to execute manipulatory finger movements under experimentally induced ischemia causing paralysis of the hand also strongly suppressed 20-Hz activity but did not affect the somatosensory evoked response. The results indicate that the primary motor cortex is involved in motor imagery. Both imaginative and executive motor tasks appear to utilize the cortical circuitry generating the somatomotor 20-Hz signal.

Magnetoencephalographic cortical rhythms.

We have characterized the magnetic 10- and 20-Hz rhythms recorded with a whole-scalp neuromagnetometer during different conditions. Sources of the posterior 10-Hz (alpha) rhythm clustered mainly around the parieto-occipital sulcus and, to a lesser extent, around the calcarine sulci, with several generators. Temporal Spectral Evolution (TSE) analysis, used to follow event-related changes in the different frequency bands, showed strong dampening of the alpha within 200 ms after the appearance of a visual stimulus and also during visual imagery. Suppression was often followed by a rebound above the baseline level. The rolandic mu rhythm consisted of 10- and 20-Hz components with different reactivity and source locations. The 10-Hz component seems to be mainly somatosensory in origin whereas the 20-Hz signal also receives contributions from the motor cortex, and even shows 'motorotopy' in its reactivity: the source locations depend in a somatotopical manner on the site of the moving body part. The frequency composition of the posterior spontaneous activity was disturbed in patients with small infarcts of the medial thalamus. It is shown with simulations that a surprisingly small number of synchronized cortical neurons could generate the major part of the recorded oscillatory signal. Finally, some clarifications are suggested to the terminology of brain rhythms.

Modulation of human cortical rolandic rhythms during natural sensorimotor tasks.

We studied modulation of cortical neuromagnetic rhythms in association with left and right median nerve stimulation, during rest, finger movements, and passive tactile hand stimulation, in seven healthy, right-handed adults. In the rest condition, the amplitude of the rhythmic sensorimotor activity decreased immediately after the median nerve stimuli and increased above the prestimulus level within 0.4 s afterward, especially in the 7- to 25-Hz band. The rebound occurred 100-300 ms earlier for 20 (7-15)-than for 10 (15-25)-Hz activity. Suppressions and rebounds were strongest in the contralateral sensorimotor hand area for the 20-Hz, but not for the 10-Hz, activity. The maximum rebound was on average 22-34% stronger in the left than in the right hemisphere. Active exploration of objects abolished rebounds of both 10- and 20-Hz signals in the contralateral hemisphere and markedly diminished them ipsilaterally. Finger movements without touching an object and passive tactile stimulation produced a weaker effect. The sensorimotor rhythms thus show a characteristic suppression and subsequent rebound after electrical median nerve stimulation. The rebound is left-hemisphere dominant in right-handed subjects and its suppression reveals bilateral cortical activation during both motor tasks and passive tactile stimulation, especially for explorative finger movements.

Evidence for reactive magnetic 10-Hz rhythm in the human auditory cortex.

We tested the hypothesis that neurons in the human auditory cortex show spontaneous oscillations around 10 Hz, and that this activity ('tau' rhythm) is affected by auditory input. Cortical activity was recorded with a 122-channel whole-scalp neuromagnetometer from healthy adults while they were presented with monaural 500-ms bursts of white noise. The reactivity of spontaneous oscillations was studied over the whole cortex using the Temporal Spectral Evolution method. Oscillatory 6.5-9.5 Hz activity, with sources in the superior temporal lobes, was transiently suppressed by the sounds in eight out of nine subjects. Our results support the existence of a distinct, reactive auditory rhythm in the human temporal cortex.

Human cortical oscillations: a neuromagnetic view through the skull.

The mammalian cerebral cortex generates a variety of rhythmic oscillations, detectable directly from the cortex or the scalp. Recent non-invasive recordings from intact humans, by means of neuromagnetometers with large sensor arrays, have shown that several regions of the healthy human cortex have their own intrinsic rhythms, typically 8-40 Hz in frequency, with modality- and frequency-specific reactivity. The conventional hypotheses about the functional significance of brain rhythms extend from epiphenomena to perceptual binding and object segmentation. Recent data indicate that some cortical rhythms can be related to periodic activity of peripheral sensor and effector organs.

Human cortical 40 Hz rhythm is closely related to EMG rhythmicity.

We recorded cortical neuromagnetic rhythms during self-paced index-finger movements from a subject previously reported to show prominent 40 Hz electroencephalographic activity during motor behavior. The 10 and 20 Hz components of the rolandic mu rhythm were bilaterally suppressed, whereas the contralateral 40 Hz (35-41 Hz) activity was slightly enhanced before both fast and slow movements and strongly enhanced during slow movements. The 40 Hz rhythm originated mainly in the hand motor cortex and was clearly correlated with the rhythmicity of the electromyogram from the extensor muscles, with a systematic time lag. In this subject motor preparation, and especially control of finger movements, may thus be associated with enhanced cortical rhythms near 40 Hz. The coherence of these rhythms with muscular firing patterns likely reflects communication between the sensorimotor cortex and the motor units.

Odorants activate the human superior temporal sulcus.

The human olfactory pathways are well defined up to the level of the prepiriform cortex but the neocortical projections and their functional organization are still largely unknown. We recorded whole-scalp neuromagnetic signals to olfactory stimulation with boluses of phenylethyl alcohol, hydrogen sulphide, and vanillin. The main magnetic response peaked about 700 ms after the stimulus onset. The three odorants activated overlapping cortical areas around the superior temporal sulci of both hemispheres, revealing a neocortical area involved in olfactory processing.

Functional segregation of movement-related rhythmic activity in the human brain.

Multiple synaptic interconnections in the human brain support concerted rhythmic activity of a large number of cortical neurons, typically close to 10 and 20 Hz. Our present neuromagnetic data provide evidence for distinct functional roles of these spectral components in the somatomotor cortex. The sites of suppression during movement and the subsequent rebound of the 20-Hz rhythm followed, along the motor cortex, the representation of fingers, toes, and mouth, as opposed to the stable origin of the 10-Hz rhythms close to the hand somatosensory cortex. The 20-Hz activity appears to be a signature of active immobilization following movement, whereas the reactive 10-Hz signals likely reflect lack of relevant sensory input from the important upper limbs.