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At least 757 records · Page 42Linked to original sources
PubMed1994

Effect of DNA-repair-enzyme modulators on cytotoxicity of L-phenylalanine mustard and cis-diamminedichloroplatinum (II) in mammary carcinoma cells resistant to alkylating drugs.

We investigated the effect of DNA-repair-enzyme inhibitors on L-phenylalanine mustard (L-PAM) and cis-diamminedichloroplatinum (II) (CDDP) cytotoxicity in rat mammary-carcinoma MatB cells sensitive (WT) and resistant (MLNr) to bifunctional alkylating drugs. Among the modulators tested, the combination of arabinofuranosylcytosine (Ara-C) and hydroxyurea (HU) significantly increased the sensitivity of the cells to CDDP and, to a lesser extent, L-PAM as compared with cells treated with drug alone. The modulation effect of HU+Ara-C on CDDP and L-PAM cytotoxicity was more effective when intracellular glutathione (GSH) was depleted by L-buthionine-(S,R)-sulfoximine (BSO). This was also associated with a significant increase in DNA-DNA interstrand cross-links. Caffeine also sensitized both WT and MLNr cells to the cytotoxic effect of L-PAM and CDDP, and this effect was potentiated in GSH-depleted cells. No significant effect was observed with other repair modulators such as aphidicolin, 3-aminobenzamide, novobiocin, or etoposide. These results show (a) that inhibition of DNA repair by HU+Ara-C or caffeine could be a target for modulation of bifunctional alkylating-drug resistance and (b) that GSH depletion renders resistant cells more susceptible to the repair-enzyme modulators, suggesting that intracellular GSH may be involved in the regulation of some of these enzymes. Our results also indicate that a combination of a number of modulators may offer an advantage over the use of a single modulator in tumor resistance that may be associated with multifactorial mechanisms.

Adenocarcinoma↗
PubMed1994

Spectra of data sampled at frequency-modulated rates in application to cardiovascular signals: Part 2. Evaluation of Fourier transform algorithms.

For three direct Fourier transform algorithms we quantified the influence of pulse frequency modulation (PFM) on the spectral estimation of pulse amplitude modulation (PAM). The simulation study is based on sinusoid functions sampled according to a pulse sequence which is the output of an integral pulse frequency modulator (IPFM). One algorithm exactly reproduces the theoretical spectrum derived in Part 1. The other two, including the classical FFT, scale all PFM-induced components in a different way, and in addition, generate higher modulating frequency harmonics. For a PFM depth below 30%, the sum of spurious PFM components is almost linearly dependent on this modulation depth, for all three algorithms. Dividing the effect of PFM in a 'harmonic' and 'aliasing' distortion, we found that the FFT has a relatively high harmonic distortion, compared to an algorithm that takes into account the non-uniform character of the data. In the cardiovascular (worst) case of 30% modulation in heart rate (PFM) at a frequency of 0.1 Hz, the FFT spectrum of beat-to-beat systolic blood pressure variations contains approximately 20% of spurious components caused solely by the modulation in time occurrences of the blood pressure samples. The 'non-uniform' algorithm performs twice as well in this case.

Algorithms↗
PubMed2001

Application of plasma gas modulation technique for improvement of the measurement of Mn emission intensity in ICP-AES.

A phase-sensitive detection technique associated with a digital lock-in amplifier was applied for an improvement of the detection in ICP-AES. The lock-in amplifier works as an extremely narrow band pass filter. It can pick up the modulated signal, which has the same frequency as the reference signal, from any noise and thus it can improve the signal-to-noise ratio. Modulation of the ICP can be performed by mixing small amounts of air to argon as the outer gas cyclically, because the emission intensities of ionic lines are enhanced by using the mixed gas. An electromagnetic valve, which is placed in the outer-gas flow path, causes periodic variation in the air gas in the outer-gas flow, and thus switching the valve on/off can modulate the ICP. By choosing the appropriate conditions, the addition of air gas enhances the emission intensity of ionic lines more than that of the background, thus leading to improved signal-to-background ratios. At the same time the lock-in amplifier further enhances the ionic emissions because it picks up only the modulated part of the signal. By applying the plasma gas flow modulation technique the detection and the determination limits of the Mn II 257.610 nm line are improved in comparison with the conventional method. A change in plasma shape corresponding to the modulation frequency is observed when the ICP is modulated.

Journal Article↗
PubMed2006

Modulation of soleus H-reflexes during gait in healthy children.

During locomotion spinal short latency reflexes are rhythmically modulated and depressed compared to rest. In adults this modulation is severely disturbed after bilateral spinal lesions indicating a role for supra-spinal control. Soleus reflex amplitudes are large in the stance phase and suppressed in the swing phase contributing to the reciprocal muscle activation pattern required for walking. In early childhood the EMG pattern during gait underlies an age-dependent process changing from co-contraction of agonists and antagonists to a reciprocal pattern at the age of 5-7 years. It is unknown whether at this stage apart from the EMG also reflexes are modulated, and if so, whether the reflex modulation is fully mature or still underlies an age-dependent development. This may give important information about the maturation of CNS structures involved in gait control. Soleus Hoffmann H-reflexes were investigated in 36 healthy children aged 7-16 years during treadmill walking at 1.2 km/h and 3.0 km/h. At 7 years old a rhythmic modulation similar to adults was observed. The H-reflex size during the stance phase decreased significantly with age while the maximum H-reflex (H (max)) at rest remained unchanged. At 3.0 km/h H-reflexes were significantly larger during the stance phase and smaller during the swing phase as compared to 1.2 km/h but the age-dependent suppression was observed at both walking velocities. In conclusion H-reflex modulation during gait is already present in young children but still underlies an age-dependent process independent of the walking velocity. The finding that the rhythmic part of the modulation is already present at the age of 7 years may indicate that the supra-spinal structures involved mature earlier than those involved in the tonic reflex depression. This may reflect an increasing supra-spinal control of spinal reflexes under functional conditions with maturation.

Adolescent↗
PubMed2002

Responses of chinchilla inferior colliculus neurons to amplitude-modulated tones with different envelopes.

Responses of single neurons in the inferior colliculus of the chinchilla to amplitude-modulated tones were obtained. In one condition, the modulating waveform was a low-frequency sinusoid (SAM tone). In the other, the modulator was a trapezoid with fixed parameters, used to create trains of brief tone bursts presented at various repetition rates (TRAM tone). Modulation frequency (or repetition rate) was varied over the range from 10 to 200 Hz. Many individual neurons exhibited strong selectivity for modulator type. Neurons with pauser discharge patterns to steady-state tones usually exhibited greater responsiveness to SAM tones than to TRAM. In contrast, neurons that responded transiently to steady-state tones usually exhibited greater responsiveness to TRAM tones than to SAM. Neurons with sustained responses to steady-state tones responded strongly to both types of modulated tones. The selectivity for modulator type suggests that transient neurons may play a different functional role in the representation of envelopes than do other types of neurons.

Acoustic Stimulation↗
PubMed2007

Effect of language and task demands on the diagnostic effectiveness of the autism diagnostic observation schedule: the impact of module choice.

The ADOS characterizes socio-communicative deficits in autism spectrum disorders (ASD). In this study the effect of module choice on ADOS classification was examined. For 74 participants (52 autism, 22 PDD-NOS), Module 1 and Module 2 were administered in a single session. Fifty-one participants maintained ADOS classification, with 17 more impaired on M2 and 6 more impaired on M1. For 64 participants (25 autism, 39 PDD-NOS), Module 2 and Module 3 were administered. Thirty-nine participants maintained classification, with 24 more impaired on M3 and 1 more impaired on M2. As expected, more impairment was indicated when a module with more language and task demands was administered. Clinical judgment of the most appropriate module for administration was found to be important.

Autistic Disorder↗
PubMed1986

Isolation and characterization of two 70 kDa modulator-complexes from rabbit skeletal muscle.

The activation as well as the inactivation of the ATP,Mg-dependent protein phosphatase has been shown to be totally dependent upon the presence of the modulator subunit. This modulator (inhibitor-2) is a heat stable protein and its isolation in pure form (32 kDa) always includes a boiling step. The boiled modulator fractions are known to be inhibitory to the phosphatase activity. Unboiled rabbit skeletal muscle preparations do not contain "free modulator", but two higher molecular weight complexes (70 kDa) can be isolated which have the 32 kDa modulator together with a 38 kDa protein. One complex is the already characterized inactive ATP,Mg-dependent phosphatase [FCM] while the second one, [MX], although seemingly of identical composition, does not exhibit phosphatase activity when measured under the usual conditions. The MX-complex does not inhibit the phosphatase activity unless subjected to a boiling step which dissociates the modulator subunit. The unboiled [MX] exhibits the activation as well as the inactivation characteristics of the free modulator.

Animals↗
PubMed1992

Effects of the modulating agent WR2721 and its main metabolites on the formation and stability of cisplatin-DNA adducts in vitro in comparison to the effects of thiosulphate and diethyldithiocarbamate.

The influence of the modulating agent WR2721, its active thiol-metabolite WR1065 and the symmetrical disulphide WR33278 on the in vitro formation and stability of cis-diamminedichloroplatinum(II) (cisplatin, CDDP)-DNA adducts was investigated and compared with the effects of the highly nucleophilic modulating agents diethyldithiocarbamate (DDTC) and thiosulphate (TS). Salmon sperm DNA (0.5 mg/mL) was incubated with 25 micrograms/mL (83 microM) cisplatin for 1 hr in 50 mM phosphate buffer, pH 7.2 at 37 degrees in the absence or presence of modulating agent. DDTC and TS were potent inhibitors of the platination of the DNA (95 and 89%, respectively, with 4.2 mM of modulating agent). The WR-compounds were also remarkably active in the inhibition of DNA platination. Prevention of adduct formation in the presence of 4.2 mM WR-compound decreased in the order WR1065 (74%) greater than WR33278 (63%) greater than WR2721 (51%). The prevention of CDDP-DNA adduct formation by WR1065 was strongly concentration-dependent up to 4.2 mM but at higher concentrations this protection hardly increased at all. In the presence of the modulating agents, increased levels of CDDP monofunctionally bound to a guanine residue were observed with a simultaneous decrease in the relative abundance of bifunctional adducts. All modulators were also able to reverse part of the CDDP-DNA adducts formed. After a 2-hr incubation of already platinated salmon sperm DNA with 4.2 mM of modulating agent, the removal of Pt from DNA amounted to about 43% with DDTC, 28% with WR1065 and 13-14% with TS, WR2721 and WR33278. Even CDDP bifunctionally bound to two adjacent guanines in the same DNA strand, which is considered to be a very stable adduct, was partly reversed. Our observations suggest that WR2721, especially when administered prior to or concomitantly with CDDP, can be expected to protect those tissues from CDDP-induced damage to DNA that are able to efficiently dephosphorylate WR2721 followed by uptake of the thiol metabolite WR1065. This stresses the importance of a selective formation and uptake of WR1065 by non-tumour tissues for the successful use of WR2721 as a protective agent in combination with platinum-based cancer chemotherapy.

Amifostine↗
PubMed1996

Loreclezole modulates [35S]t-butylbicyclophosphorothionate and [3H]flunitrazepam binding via a distinct site on the GABAA receptor complex.

The allosteric modulation of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) and [3H]flunitrazepam binding was utilized to evaluate the actions of loreclezole at the GABAA receptor complex in the rat brain. Loreclezole was observed to allosterically inhibit the binding of [35S]TBPS in a dose-dependent manner with micromolar potency (IC50 = 1 microM). Loreclezole was found to have an additive effect on neuroactive steroid modulation of [35S]TBPS binding, but merely potentiated the effect of Ro5-4864 (4"-chlorodiazepam) modulation of [35S]TBPS binding. These observations suggest that loreclezole modulates [35S]TBPS binding through a site independent of the neuroactive steroid and Ro5-4864 sites on the GABAA receptor complex. The enhancement of [3H]flunitrazepam binding to the benzodiazepine receptor by loreclezole as well as the effect of loreclezole on CL218872/[3H]flunitrazepam dose-response curves suggest that loreclezole does not act through the benzodiazepine site on the GABAA receptor complex, nor does it selectively modulate benzodiazepine receptor subtypes. The potency of loreclezole as and inhibitor of [35S]TBPS binding in rat brain was regionally dependent and GABA-sensitive. Loreclezole modulation of [35S]TBPS binding showed greater potency and GABA sensitivity in the cerebellum and thalamus when compared to other brain regions such as the cortex, hippocampus and striatum. This finding is consistent with previous reports of the selectivity of loreclezole for GABAA receptor complex's containing beta 2 and beta 3 subunits. These beta subunit isoforms predominate in the cerebellum and thalamus. Collectively the evidence suggests that loreclezole modulates [35S]TBPS and [3H]flunitrazepam binding through a site distinct from benzodiazepine, neuroactive steroid, Ro5-4864 and GABA sites on the GABAA receptor complex.

Animals↗
PubMed1996

Visual modulation of air righting by rats involves calculation of time-to-impact, but does not require the detection of the looming stimulus of the approaching ground.

Rats do not visually trigger righting when falling supine in the air. They can, however, use vision to modulate the time of onset of air righting depending upon the height from the ground from which they are dropped. That is, the shorter the height, the quicker they begin to right. The visual cortex has been shown not to be necessary for such modulation; however, such modulation is absent if the superior colliculus is damaged. It is known that the superior colliculus has cells that respond to looming stimuli, and this could be the mechanism for modulation during air righting. In this study, 3 experiments were conducted to test this possibility. The evidence from all 3 suggests that something other than detecting a looming stimulus (i.e., the oncoming ground) is involved in the rats' determination of when to initiate righting. Expt. 1 showed that the ability to modulate the onset of air righting visually is not mature until adulthood (> 80 days). Yet young rats do respond to looming stimuli. Exp. 2 showed that the ability to modulate the onset of air righting requires both eyes. One eye should be sufficient to detect a looming stimulus. Expt. 3 showed that the rats require visual information prior to being dropped, not after, in order to modulate the onset of air righting. If the looming stimulus were the triggering stimulus, then this would be detected after, not before, being dropped. These findings suggest that the rats' ability to calculate the time-to-impact when falling involves a more complex calculation than simply detecting the presence of a looming stimulus.

Aging↗
PubMed1982

Theory of phase-modulation fluorescence spectroscopy for excited-state processes.

Theory is presented for the analysis of excited-state reactions by fluorescence phase shift and demodulation methods. Initially, a two-state model with spectral overlap is considered to illustrate most simply the effects of excited-state reactions on the expected phase and modulation values. Secondly, a multistate model is described to illustrate the probable effects of a fluorophore interacting with several solvent molecules. We note the following unique features of phase-modulation data expected from a fluorophore whose emission spectrum shifts during the lifetime of the excited state: (1) The modulation frequency dependence of the apparent phase (tau p) and modulation (tau m lifetimes of the reacted species is opposite to that of a heterogeneous population of fluorophores. (2) For the reacted species tau p greater than tau m. For a heterogeneous sample tau p less than tau m. (3) The phase angle of the reacted species can exceed 90 degrees. For a heterogeneous sample phase angles are always less than 90 degrees. Thus, phase and modulation measurements can distinguish between time-dependent processes and spectral heterogeneity by observation of any feature described above. Additionally: (4) The lifetime of the product species can be measured directly. (5) Reverse relaxation can be identified, and the reverse relaxation rates calculated. (6) The wavelength-dependent phase and modulation data can be used to resolve the individual spectra from a two-state reaction. (7) And finally, under favorable conditions, a two-state excited-state process can be distinguished from a continuous multiple-state process. In each instance, model calculations are presented to illustrate the unique potentials of phase-modulation fluorometry for investigations of excited-state processes.

Kinetics↗
PubMed1982

Fluctuation strength and temporal masking patterns of amplitude-modulated broadband noise.

Fluctuation strength of sinusoidally amplitude modulated broadband noise was measured by a magnitude-estimation procedure. Fluctuation strength shows, as a function of modulation frequency, a bandpass characteristic with a maximum around 4 Hz. With increasing modulation depth and sound pressure level, fluctuation strength increases. For the same stimulus parameters as used in the experiments on fluctuation strength, temporal masking of amplitude modulated broadband noise was determined. The level difference delta L between the maximum and the minimum of the resulting temporal masking patterns shows a low-pass characteristic as a function of modulation frequency and increases with increasing modulation depth and sound pressure level. A model of fluctuation strength F based on the depth delta L of the temporal masking pattern and the modulation frequency fmod in relation to 4 Hz is proposed as follows: F approximately delta L/((fmod/4 Hz)+(4 Hz/fmod)). The model accounts for the dependence of fluctuation strength on some essential stimulus parameters. The usefulness of temporal masking patterns as an intermediate value for the description of hearing sensations is confirmed.

Adult↗
PubMed1992

Coherence of frequency modulation is encoded by cochlear-generated distortion.

Nonlinearities of the peripheral auditory system generate distortion products which present to the central auditory system as apparent acoustic stimuli. The frequency and amplitude of distortion products reflect the frequency, phase and amplitude relationship of the components of a complex stimulus. When the stimulus consists of harmonically-related primaries, the amplitudes of the major distortion products are a function of the relative phase of the presented (primary) tones. We have previously shown (McAnally and Calford, 1990) that the variation of amplitude of the distortion as a function of the relative phase of a pair of harmonically-related primaries is well modelled as a function of the interaction of the multiple modes of distortion which fall at the same frequency (e.g. difference frequency and cubic difference frequency). A possibility raised by this result is that coherence of frequency modulation (that which maintains harmonicity) could be encoded in the amplitude of distortion. This was examined in measurements of both the cochlear microphonic potential (CM) and the responses of auditory nerve fibres in anaesthetized cats. Very small deviations from coherence of frequency modulation produced changes in the amplitude of the CM potential at the frequency of distortion. Also the discharges of auditory nerve fibres tuned to the frequency of distortion were found to be modulated at the same frequency as the amplitude changes observed in the CM. There was no variation in distortion amplitude in the CM and no modulation of auditory nerve discharges when primaries were frequency modulated coherently. It is suggested that amplitude modulation of distortion gives the auditory system its demonstrated sensitivity to minor departures from coherence of frequency-modulated, harmonically-related tones.

Acoustic Stimulation↗
PubMed1993

Reversal of multidrug resistance by a new lipophilic cationic molecule, S9788. Comparison with 11 other MDR-modulating agents in a model of doxorubicin-resistant rat glioblastoma cells.

We have compared the properties of the novel multidrug resistance modulator, S9788, to a panel of 11 well-known modulators in a model of rat glioblastoma cells resistant to doxorubicin and displaying a P-glycoprotein-mediated multidrug-resistance phenotype complemented by a mechanism of intracellular drug tolerance not yet identified (Br J Cancer 1992, 65, 538-544). S9788, like most modulators, was able to completely restore drug accumulation in the resistant line to the level obtained in the sensitive cells. This was obtained with 10 mumol/l of modulator, which is slightly higher than required for cyclosporine A (3 mumol/l) verapamil and nicardipine (6 mumol/l), but lower than for amiodarone, trifluoperazine and dipyridamole (20 mumol/l), tamoxifen and diltiazem (40 mumol/l), quinine, quinidine and nifedipine (> 100 mumol/l). Complete restoration of drug cytotoxicity was, however, obtained only with amiodarone, and a residual resistance factor of 4 could not be overcome by cyclosporine A or S9788, while other modulators gave residual resistance factors of 5-20 (trifluoperazine, tamoxifen, verapamil, quinine, nicardipine, dipyridamole) or even higher (diltiazem, quinidine, nifedipine). When studying doxorubicin accumulation obtained for an exposure to the IC50 of this drug, it appeared that some modulators were able to decrease this "intracellular IC50" independently of their efficiency in resistance reversal (cyclosporine A, S9788, amiodarone, trifluoperazine, quinine, tamoxifen), thus reversing intracellular drug tolerance, whereas other modulators could not reduce this parameter (verapamil, nicardipine, dipyridamole, diltiazem, quinidine). It is suggested that drugs of the first group could be able to segregate doxorubicin in subcellular compartments from which it could not reach its nuclear targets.

Animals↗
PubMed2006

Screening for positive allosteric modulators of biological targets.

The benefit of using positive allosteric modulators of protein function in the therapy of human diseases is becoming more apparent. The advantage of positive allosteric modulators is that they can possess specificity and selectivity profiles as well as concentration-independent limits on activity that can significantly reduce off-target effects in vivo. However, many current screening paradigms are not designed to discover positive allosteric modulators, and modulators that are discovered serendipitously can be overlooked during the hit-picking process. The conditions needed to discover positive allosteric modulators in a HTS are reasonable and simple to implement, generally requiring consideration of the ligand concentration in a screen. Other considerations in the screening for positive allosteric modulators can be derived from the analysis of simple kinetic schemes that describe the interactions of ligands and modulators with different protein targets.

Allosteric Regulation↗
PubMed2005

Corticofugal modulation of directional sensitivity in the midbrain of the big brown bat, Eptesicus fuscus.

In our recent study of corticofugal modulation of collicular amplitude sensitivity of the big brown bat, Eptesicus fuscus, we suggested that the corticofugal modulation is based upon the best frequency (BF) differences and the relative amplitude sensitivity difference between collicular (IC) and cortical (AC) neurons but not the absolute amplitude sensitivity of IC and AC neurons. To show that corticofugal modulation is systematic and multiparametric, we studied corticofugal modulation of directional sensitivity in 89 corticofugally inhibited IC neurons in the same bat species under free field stimulation conditions. A neuron's directional sensitivity was expressed with the azimuthal range (AR) at 50% below the maximum of each directional sensitivity curve and the best azimuth (BAZ) at which the neuron discharged maximally. Cortical electrical stimulation did not affect the directional sensitivity of 40 (45%) neurons with BF(IC-AC) differences of 7.3+/-4.4kHz but sharpened the directional sensitivity of other 49 (55%) neurons with BF(IC-AC) differences of 2.3+/-1.8kHz. Corticofugal modulation sharpened directional sensitivity curves of IC neurons by decreasing the AR and shifting collicular BAZ toward cortical BAZ. The decrease in AR and the shift in BAZ increased significantly with AR(IC-AC) and BAZ(IC-AC) differences but not with absolute AR and BAZ of IC and AC neurons or BF(IC-AC) differences. Corticofual modulation also shifted collicular BF toward cortical BF. The shift in BF increased significantly with BF(IC-AC) differences but not with the BF of IC and AC neurons or BAZ shift. Consonant with our previous study, these data indicate that corticofugal modulation of collicular directional sensitivity is based on topographic projections between the IC and the AC and the difference in directional sensitivity but not the absolute directional sensitivity of IC or AC neurons.

Acoustic Stimulation↗
PubMed2006

Modulation of inhibitory glycine receptors in cultured embryonic mouse hippocampal neurons by zinc, thiol containing redox agents and carnosine.

Modulation of inhibitory glycine receptors by zinc (Zn(2+)) and endogenous redox agents such as glutathione may alter inhibition in the mammalian brain. Despite the abundance of Zn(2+) in the hippocampus and its ability to modulate glycine receptors, few studies have examined Zn(2+) modulation of hippocampal glycine receptors. Whether redox agents modulate hippocampal glycine receptors also remains unknown. This study examined Zn(2+) and redox modulation of glycine receptor-mediated currents in cultured embryonic mouse hippocampal neurons using whole-cell recordings. Zn(2+) concentrations below 10 microM potentiated currents elicited by low glycine, beta-alanine, and taurine concentrations by 300-400%. Zn(2+) concentrations above 300 microM produced nearly complete inhibition. Potentiating Zn(2+) concentrations shifted the dose-response curves for the three agonists to the left and decreased the Hill coefficient for glycine and beta-alanine but not taurine. Inhibiting Zn(2+) concentrations shifted the dose-response curves for glycine and beta-alanine to the right but reduced the maximum taurine response. Histidine residues may participate in potentiation because diethyl pyrocarbonate and pH 5.4 diminished Zn(2+) enhancement of glycine currents. pH 5.4 diminished Zn(2+) block of glycine currents, but diethyl pyrocarbonate did not. These findings indicate that separate sites mediate Zn(2+) potentiation and inhibition. The redox agents glutathione, dithiothreitol, tris(2-carboxyethyl)phosphine, and 5,5'-dithiobis(2-nitrobenzoic acid) did not alter glycine currents by a redox mechanism. However, glutathione and dithiothreitol interfered with the effects of Zn(2+) on glycine currents by chelating it. Carnosine had similar effects. Thus, Zn(2+) and thiol containing redox agents that chelate Zn(2+) modulate hippocampal glycine receptors with the mechanism of Zn(2+) modulation being agonist dependent.

Animals↗
PubMed2004

Cognitive modulation of pain-related brain responses depends on behavioral strategy.

Interactions of pain and cognition have been studied in humans and animals previously, but the relationship between such behavioral interactions and brain activity is unknown. We aimed to show using functional MRI (fMRI) how a cognitively demanding task (Stroop) modulates pain-related brain activations and conversely, how pain modulates attention-related activity. Reaction time data indicated two types of pain responders: subjects in the A group had a faster Stroop reaction time when pain was concomitant to the attention task, while those in the P group had a slower Stroop performance during painful stimulation. fMRI data obtained during Stroop performance with and without noxious stimulation were subjected to region of interest analyses. We first tested whether brain activity during painful median nerve stimulation was modulated by cognitive load. We next tested whether brain activity during the high conflict cognitive task was modulated by pain. Pain-related activity in three regions, primary (S1), and secondary (S2) somatosensory cortices, and anterior insula, was attenuated by cognitive engagement, but this effect was specific to the A group. Pain-related activations in the caudal and rostral anterior cingulate cortex (ACC) and ventroposterior thalamus were not modulated by cognitive load. None of the areas showing attention-related responses, including bilateral dorsolateral prefrontal and posterior parietal cortices, were modulated by pain. These findings suggest that cortical regions associated with pain can be modulated by cognitive strategies. Furthermore, the distinction of behavioral subgroups may relate to cognitive coping strategies taken by patients with chronic pain.

Adult↗