Intensity-response Curves Research Articles

Rainfall events and daily mortality across 645 global locations: two stage time series analysis

ObjectiveTo examine the associations between characteristics of daily rainfall (intensity, duration, and frequency) and all cause, cardiovascular, and respiratory mortality.DesignTwo stage time series analysis.Setting645 locations across 34 countries or regions.PopulationDaily...

In-fiber illumination-detection-synchronized confocal microscopy for high-precision fast axial scanning

Confocal microscopy remains a major workhorse in the 3D surface topography measurement owing to its reliability and compatibility for workpieces with various reflectance, which, however, suffers from slow scanning speed and limited axial resolution. Commercial confocal microscopy primarily relies on the axial movement of a sample or objective lens to create a series of 2D image stacks, and then reconstruct 3D map. Nevertheless, most samples and objective lens are too bulky to scan rapidly, let alone that multiple scans are required to increase the signal-to-noise ratio (SNR). To address this issue, an original approach named illumination-detection-synchronized confocal microscopy was developed, which enabled high-precision fast axial scanning via a compact fiber-multiplexed port with the high-speed synchronous motion of point source and point detection. The approach can effectively improve the peak localization precision while not requiring a high-precision motion stage. Theoretically, via controlling the magnification of the optical system M > 1, the total peak localization precision of axial light intensity response curve can be improved by M3 times. Experiments show that the single-point repeat measurement precision by this approach is improved by 4 times, and the profile measurement precision is enhanced by 2.3 times. Moreover, this approach can effectively avoid collisions between the sample and objective lens, and has the potential to design a low-cost single-point confocal sensor or confocal profilometer.

Trans-spinal magnetic stimulation induces co-activation of the diaphragm and biceps in healthy subjects.

The present study was designed to examine the effect of trans-spinal magnetic stimulation on bilateral respiratory and forelimb muscles in healthy subjects. Two wings of a figure-of-eight magnetic coil were placed on the dorsal vertebrae, from the fifth cervical to the second thoracic dorsal vertebra with a center at the seventh cervical vertebra. The surface electromyograms of bilateral diaphragm and biceps were recorded in response to trans-spinal magnetic stimulation with 20%-100% maximum output of the stimulatory device in male (n = 12) and female participants (n = 8). Trans-spinal magnetic stimulation can induce a co-activation of bilateral diaphragm and biceps when the stimulation intensity is above 60%. The onset latency was comparable between the left and right sides of the muscles, suggesting bilateral muscles could be simultaneously activated by trans-spinal magnetic stimulation. In addition, the intensity-response curve of the biceps was shifted upward compared with that of the diaphragm in males, indicating that the responsiveness of the biceps was greater than that of the diaphragm. This study demonstrated the feasibility of utilizing trans-spinal magnetic stimulation to co-activate the bilateral diaphragm and biceps. We proposed that this stimulatory configuration can be an efficient approach to activate both respiratory and forelimb muscles.

Multiple rod layers increase the speed and sensitivity of vision in nocturnal reef fishes.

Most vertebrates have one layer of the dim-light active rod photoreceptors. However, multiple rod layers, known as a multibank retina, can be found in over 100 species of fish, including several deep-sea species and one family of nocturnally active reef fish, the Holocentridae. Although seemingly associated with increased photon catch, the function of multibank retinas remained unknown. We used an integrative approach, combining histology, electrophysiology and amino acid sequence analysis, applied to three species of nocturnal reef fishes, two holocentrids with a multibank retina (Neoniphon sammara and Myripristis violacea) and an apogonid with a single rod bank (Ostorhinchus compressus), to determine the sensory advantage of multiple rod layers. Our results showed that fish with multibank retinas have both faster vision and enhanced responses to bright- and dim-light intensities. Faster vision was indicated by higher flicker fusion frequencies during temporal resolution electroretinography as well as faster retinal release rates estimated from their rhodopsin proteins. Enhanced sensitivity was demonstrated by broadened intensity-response curves derived from luminous sensitivity electroretinography. Overall, our findings provide the first functional evidence for enhanced dim-light sensitivity using a multibank retina while also suggesting novel roles for the adaptation in enhancing bright-light sensitivity and the speed of vision.

Nonlinear phase error correction method based on multi-grayscale coding.

Fringe projection profilometry is a non-contact and highly efficient 3D measurement technique widely used in various applications. However, the nonlinear intensity response of digital projectors affects measurement accuracy. While increasing the number of fringe projections can reduce the errors caused by nonlinear problems, it significantly prolongs the measurement time. In order to improve both accuracy and speed simultaneously, a nonlinear phase error correction method based on multi-grayscale coding is proposed. The intensity response curve of the system is fitted by the grayscale images, and then the grayscale values of the phase-shifting fringe images are corrected to reduce the nonlinear error. In order to reduce the number of fringe projections and speed up the measurement, the multi-grayscale coding method is used to divide the phase interval by the order of the gray values of the same pixel in multiple grayscale images. The experimental results validate the efficacy of the proposed multi-grayscale coding method. An accurate phase calculation is achieved, and a single reconstruction can be achieved with only seven photos. After the nonlinear correction, the phase accuracy of the three-step phase-shifting algorithm is increased by 50.77%, and the reconstruction accuracy of the standard ball is increased by 46.38%.

Co-activation of diaphragm and bicep in response to trans-spinal magnetic stimulation in healthy males

Magnetic stimulation is a non-invasive approach to activate the neural tissue and induce the motor evoked potential. Diaphragm and bicep are innervating by motoneurons located within the mid-cervical spine cord; thus, the present study was designed to evaluate whether trans-spinal magnetic stimulation can co-activate the diaphragm and bicep in healthy male subjects (n=12) (KMUHIRB-F(I)-20210039). The two wings of the figure-of-eight magnetic coil (MCF-B65, inner diameter: 35 mm; out diameter: 75 mm) were placed on the dorsal vertebrae from the fifth cervical to the second thoracic vertebral column and its handle was vertical to the spine. The surface electromyogram of the bilateral diaphragm and bicep was recorded in response to trans-spinal magnetic stimulation with 20-100% maximum output of the stimulatory device. The results showed that trans-spinal magnetic stimulation can co-activate both muscles when the stimulatory intensity reached 60%. Notably, the intensity-response curve of motor evoked potential was significantly different between diaphragm and bicep. Specifically, the normalized response curve of the bicep was generally greater than that of the diaphragm, suggesting the excitability and responsiveness of bicep were greater than that of the diaphragm during trans-spinal magnetic stimulation. In addition, the motor evoked potential of the right diaphragm and bicep was greater than the left side during low stimulatory intensity, indicating there are anatomical and/or physiological differences between left and right muscles. In conclusion, trans-spinal magnetic stimulation with two coil wings along the vertebrae can co-activate the diaphragm and bicep. This trans-spinal magnetic stimulatory configuration can be considered as a feasible and efficient neuro-rehabilitative strategy to activate muscles innervating by the cervical spinal cord in subjects with impaired respiratory and forelimb motor function. The Ministry of Science and Technology (MOST 110-2636-B-110-001 & 111-2636-B-110-001). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Differential confocal over-range determination method based on an information theory.

The existing differential confocal axial three-dimensional (3D) measurement method cannot determine whether the surface height of the sample in the field of view is within its effective measurement range. Therefore, in this paper, we propose a differential confocal over-range determination method (IT-ORDM) based on an information theory to determine whether the surface height information of the sample to be examined is within the effective measurement range of the differential confocal axial measurement. First, the IT-ORDM finds the boundary position of the axial effective measurement range by the differential confocal axial light intensity response curve. Then the effective intensity measurement ranges of the pre-focus axial response curve (ARC) and the post-focus ARC are determined by the correspondence between the boundary position and the ARC. Finally, the intersection operation of the pre-focus image of effective measurement and the post-focus image of effective measurement is used to realize the extraction of the effective measurement area of the differential confocal image. The experimental results show that the IT-ORDM can effectively determine and restore the 3D shape of the measured sample surface at the reference plane position in the multi-stage sample experiments.

Alcohol withdrawal produces changes in excitability, population discharge probability, and seizure threshold.

Alcohol withdrawal syndrome (AWS) results from the sudden cessation of chronic alcohol use and is associated with high morbidity and mortality. Alcohol withdrawal-induced central nervous system (CNS) hyperexcitability results from complex, compensatory changes in synaptic efficacy and intrinsic excitability. These changes in excitability counteract the depressing effects of chronic ethanol on neural transmission and underlie symptoms of AWS, which range from mild anxiety to seizures and death. The development of targeted pharmacotherapies for treating AWS has been slow, due in part to the lack of available animal models that capture the key features of human AWS. Using a unique optogenetic method of probing network excitability, we examined electrophysiologic correlates of hyperexcitability sensitive to early changes in CNS excitability. This method is sensitive to pharmacologic treatments that reduce excitability and may represent a platform for AWS drug development. We applied a newly developed method, the optogenetic population discharge threshold (oPDT), which uses light intensity response curves to measure network excitability in chronically implanted mice. Excitability was tracked using the oPDT before, during, and after the chronic intermittent exposure (CIE) model of alcohol withdrawal (WD). Alcohol withdrawal produced a dose-dependent leftward shift in the oPDT curve (denoting increased excitability), which was detectable in as few as three exposure cycles. This shift in excitability mirrored an increase in the number of spontaneous interictal spikes during withdrawal. In addition, Withdrawal lowered seizure thresholds and increased seizure severity in optogenetically kindled mice. We demonstrate that the oPDT provides a sensitive measure of alcohol withdrawal-induced hyperexcitability. The ability to actively probe the progression of excitability without eliciting potentially confounding seizures promises to be a useful tool in the preclinical development of next-generation pharmacotherapies for AWS.

Mechanism for Altered Dark-Adapted Electroretinogram Responses in DBA/2J Mice Includes Pupil Dilation Deficits

Purpose The DBA/2J (D2) mouse is an established model of pigmentary glaucoma, a type of primary open angle glaucoma. Prior studies have documented defects in flash electroretinogram (ERG) responses in D2 mice, but the origin of those defects is not clear. The purpose of this study was to understand the origin of these A-wave and B-wave changes in D2 ERGs. Materials and Methods To accomplish this, we analyzed the differences between 9-month-old DBA/2J-Gpnmb+ (D2-control) and D2 mouse eyes in relation to ERG responses, intraocular pressure (IOP), outer nuclear layer thickness, and pupil area. Results D2 scotopic ERGs showed lower A-wave amplitude and longer implicit time as well as a significant rightward shift in the intensity-response curve. D2 IOP increased at approximately seven months of age and had a weak correlation with the ERG A-wave sensitivity. Outer nuclear layer thickness was not significantly different in D2s compared to D2-control retinas. D2 mouse pupils also showed abnormal pupillary shape and no dilation following treatment with tropicamide eye drops. The pupil size moderately correlated with the A-wave sensitivity and this was pharmacologically replicated in C57Bl/6J mice following administration of pilocarpine to constrict the pupils. However, pilocarpine treatment did not affect ERG amplitudes. Conclusions These data suggest that the smaller pupil sizes prevented light from reaching the photoreceptors and thus contributed to reduced ERG sensitivity in D2 mice. The reduced ERG A-wave amplitude in D2 mice likely results from dysfunctional photoreceptor responses.

Rostral-Caudal Effect of Cervical Magnetic Stimulation on the Diaphragm Motor Evoked Potential after Cervical Spinal Cord Contusion in the Rat.

The present study was designed to investigate the rostral-caudal effect of spinal magnetic stimulation on diaphragmatic motor-evoked potentials after cervical spinal cord injury. The diaphragm electromyogram was recorded in rats that received a laminectomy or a left midcervical contusion at the acute (1 day), subchronic (2 weeks), or chronic (8 weeks) injury stages. The center of a figure-eight coil was placed at 30 mm lateral to bregma on the left side, and the effect of magnetic stimulation was evaluated by stimulating the rostral, middle, and caudal cervical regions in spontaneously breathing rats. The results demonstrated that cervical magnetic stimulation induced intensity-dependent motor-evoked potentials in the bilateral diaphragm in both uninjured and contused rats; however, the left diaphragm exhibited a higher amplitude and earlier onset than the right diaphragm. Moreover, the intensity-response curve was shifted upward in the rostral-to-caudal direction of magnetic stimulation, suggesting that caudal cervical magnetic stimulation produced more robust diaphragmatic motor-evoked potentials compared with rostral cervical magnetic stimulation. Interestingly, the diaphragmatic motor-evoked potentials were similar between uninjured and contused rats during cervical magnetic stimulation despite weaker inspiratory diaphragmatic activity in contused rats. In addition, in contused animals but not uninjured animals, diaphragmatic motor-evoked potential amplitudes were greater at the chronic stage than during earlier injury stages. These results demonstrated that cervical magnetic stimulation can excite the residual phrenic motor circuit to activate the diaphragm in the presence of a significant lesion in the cervical spinal cord. These findings indicate that this non-invasive approach is effective for modulating diaphragmatic excitability after cervical spinal cord injury.

Inhibition and facilitation of nociceptively evoked muscular activity by fentanyl or dexmedetomidine in isoflurane-anaesthetized pigs

ObjectiveTo investigate motor and cardiovascular responses to dexmedetomidine or fentanyl in isoflurane-anaesthetized pigs. Study designExperimental, balanced, block randomized, two-group design. AnimalsA group of 16 crossbred pigs, 55 ± 8 days (mean ± standard deviation) old. MethodsDeltoid electromyography (EMG) was recorded during isoflurane anaesthesia. Electrical stimulation using 5, 10, 20 and 40 mA of the distal right thoracic limb elicited a nociceptive withdrawal reflex (NWR), quantified by the area under the curve (AUC) for the simulation intensity versus EMG amplitude response curve. Latency to movement evoked by clamping a claw for maximum 60 seconds was noted. Arterial blood pressure and pulse rate were recorded. Data were sampled at baseline and during dexmedetomidine 0.25, 0.5, 1.0, 2.0, 4.0 and 8.0 μg kg–1 hour–1 or fentanyl 5, 10, 20, 40, 80 and 160 μg kg–1 hour–1 infusions. The influence of infusion rate on NWR AUC and spontaneous EMG was analysed using a mixed model, with p < 5%. ResultsNWR AUC increased at fentanyl 5 μg kg–1 hour–1 but decreased at fentanyl 40, 80 and 160 μg kg–1 hour–1 and dexmedetomidine 4.0 and 8.0 μg kg–1 hour–1. All pigs at fentanyl 80 μg kg–1 hour–1, and three pigs at dexmedetomidine 8.0 μg kg–1 hour–1 had mechanical latencies greater than 60 seconds. Spontaneous EMG activity increased accompanied by visually evident ‘shivering’ at fentanyl 5, 10 and 20 μg kg–1 hour–1 but decreased at dexmedetomidine 2, 4 and 8 μg kg–1 hour–1. Clinically relevant effects of increasing infusion rates on blood pressure or pulse rate were not observed. Conclusion and clinical relevanceIf anaesthetic plane or antinociception is evaluated in pigs, response to claw clamping and NWR will not necessarily give uniform results when comparing drugs. If only one method is used, results should be interpreted cautiously.

Comprehensive model and performance optimization of phase-only spatial light modulators

Several spurious effects are known to degrade the performance of phase-only spatial light modulators. We introduce a comprehensive model that takes into account the major ones: curvature of the back panel, pixel crosstalk and the internal Fabry–Perot cavity. To estimate the model parameters with high accuracy, we generate blazed grating patterns and acquire the intensity response curves of the first and second diffraction orders. The quantitative model is used to generate compensating holograms, which can produce optical modes with high fidelity.

Mass Transfer Mechanisms and Rates of CO2 and N2 in 13X Zeolite from Volumetric Frequency Response

The mass transfer mechanisms and rates of CO2 and N2 in 13X zeolite beads were determined using volumetric frequency response (VFR) methods. The VFR experiments were conducted with each gas over a wide range of frequencies from 7 × 10–5 to 9.5 Hz at 100, 200, and 750 Torr at 25 °C for CO2 and at 200, 400, and 750 Torr at 25 °C and at 40 and 55 °C at 400 Torr for N2. The resulting experimental intensity response curves were fitted to four different non-isothermal mass transfer models, including micropore diffusion, macropore gas diffusion, macropore viscous (Poiseuille) flow, and macropore surface diffusion. The resulting experimental phase lag response curves were predicted from the resulting model parameters. The macropore gas diffusion model fitted and predicted the experimental response curves the best for both gases, confirming the mass transport of both CO2 and N2 in 13X zeolite beads is macropore gas diffusion controlled. The corresponding diffusional time constant Dp/Rp2 values were 3.32 s–1 for CO...

Optogenetically-Induced Population Discharge Threshold as a Sensitive Measure of Network Excitability.

Network excitability is governed by synaptic efficacy, intrinsic excitability, and the circuitry in which these factors are expressed. The complex interplay between these factors determines how circuits function and, at the extreme, their susceptibility to seizure. We have developed a sensitive, quantitative estimate of network excitability in freely behaving mice using a novel optogenetic intensity-response procedure. Synchronous activation of deep sublayer CA1 pyramidal cells produces abnormal network-wide epileptiform population discharges (PDs) that are nearly indistinguishable from spontaneously-occurring interictal spikes (IISs). By systematically varying light intensity, and therefore the magnitude of the optogenetically-mediated current, we generated intensity-response curves using the probability of PD as the dependent variable. Manipulations known to increase excitability, such as sub-convulsive doses (20 mg/kg) of the chemoconvulsant pentylenetetrazol (PTZ), produced a leftward shift in the curve compared to baseline. The anti-epileptic drug levetiracetam (LEV; 40 mk/kg), in combination with PTZ, produced a rightward shift. Optogenetically-induced PD threshold (oPDT) baselines were stable over time, suggesting the metric is appropriate for within-subject experimental designs with multiple pharmacological manipulations.

Heterodyne confocal microscopy using symmetrical shifted-focus phase filters.

We propose a heterodyne confocal microscopy technique that uses the symmetry properties of conjugate phase-pupil filters to shift the axial intensity-response curves of two confocal systems symmetrically with respect to the geometric focal plane. A monotonic position-measuring curve is obtained by subtracting the output signals of the two confocal systems collected synchronously, while eliminating the influence of environmental noise. The system's three-dimensional tomographic ability can be improved by optimizing the pupil filter. Theoretical analyses and experiments indicate that the proposed method improves the axial and transverse resolutions of differential confocal microscopy and simplifies system installation and integration.

Localized surface plasmon resonance based U-shaped optical fiber probe for the detection of Pb2+ in aqueous medium

This work represents a detection technique of lead ion (Pb2+) in aqueous medium based on optical fiber sensor. U-shaped optical fiber is chosen for this work due to higher sensitivity and point of care capability. Oxalic acid functionalized AuNPs were coated in the sensing probe. Corresponding to variation in concentration of lead ion, output voltage, power and intensity are measured with respect to time using optical photo detector. From the linear fiting of curves, it is found that voltage, power and intensity response curve has limit of detection 1.87, 1.75 and 2.10 ppb, R2 value of 0.98, 0.99 and 0.98 with the linear range is 1–20 ppb. Other heavy metal ions have negligible effect on this sensing element, thus affirming selectivity towards lead ion. Adoption of U-shaped probe with optical detector in lieu of spectrometer makes this sensor probe compact and cost effective.

Nonlinear Regression Improves Accuracy of Characterization of Multiplexed Mass Spectrometric Assays

The need for assay characterization is ubiquitous in quantitative mass spectrometry-based proteomics. Among many assay characteristics, the limit of blank (LOB) and limit of detection (LOD) are two particularly useful figures of merit. LOB and LOD are determined by repeatedly quantifying the observed intensities of peptides in samples with known peptide concentrations and deriving an intensity versus concentration response curve. Most commonly, a weighted linear or logistic curve is fit to the intensity-concentration response, and LOB and LOD are estimated from the fit. Here we argue that these methods inaccurately characterize assays where observed intensities level off at low concentrations, which is a common situation in multiplexed systems. This manuscript illustrates the deficiencies of these methods, and proposes an alternative approach based on nonlinear regression that overcomes these inaccuracies. We evaluated the performance of the proposed method using computer simulations and using eleven experimental data sets acquired in Data-Independent Acquisition (DIA), Parallel Reaction Monitoring (PRM), and Selected Reaction Monitoring (SRM) mode. When the intensity levels off at low concentrations, the nonlinear model changes the estimates of LOB/LOD upwards, in some data sets by 20-40%. In absence of a low concentration intensity leveling off, the estimates of LOB/LOD obtained with nonlinear statistical modeling were identical to those of weighted linear regression. We implemented the nonlinear regression approach in the open-source R-based software MSstats, and advocate its general use for characterization of mass spectrometry-based assays.

The Development of Mid-Wavelength Photoresponsivity in the Mouse Retina

ABSTRACTPurpose: Photoreceptors in the mouse retina express much of the molecular machinery necessary for phototransduction and glutamatergic transmission prior to eye opening at postnatal day 13 (P13). Light responses have been observed collectively from rod and cone photoreceptors via electroretinogram recordings as early as P13 in mouse, and the responses are known to become more robust with maturation, reaching a mature state by P30. Photocurrents from single rod outer segments have been recorded at P12, but no earlier, and similar studies on cone photoreceptors have been done, but only in the adult mouse retina. In this study, we wanted to document the earliest time point in which outer retinal photoreceptors in the mouse retina begin to respond to mid-wavelength light.Methods: Ex-vivo electroretinogram recordings were made from isolated mouse retinae at P7, P8, P9, P10, and P30 at seven different flash energies (561 nm). The a-wave was pharmacologically isolated and measured at each developmental time point across all flash energies.Results: Outer-retinal photoreceptors generated a detectable response to mid-wavelength light as early as P8, but only at photopic flash energies. a-wave intensity response curves and kinetic response properties are similar to the mature retina as early as P10.Conclusion: These data represent the earliest recorded outer retinal light responses in the rodent. Photoreceptors are electrically functional and photoresponsive prior to eye opening, and much earlier than previously thought. Prior to eye opening, critical developmental processes occur that have been thought to be independent of outer retinal photic modulation. However, these data suggest light acting through outer-retinal photoreceptors has the potential to shape these critical developmental processes.

(227) - Individual differences in pain sensitivity: Insights from discriminability of graded noxious heat stimuli

The experience of pain varies for every person in both intensity and unpleasantness. The mechanisms supporting these differences in pain sensitivity are not yet understood, in part due to challenges of dissociating perceptual differences from reporting biases. In this preliminary analysis we sought to assess discriminability of graded noxious stimuli in highly sensitive and insensitive individuals. One hundred and three healthy individuals were asked to rate pain intensity and pain unpleasantness in response to a thermal stimulus paradigm containing 4 sequences of 8 semi-randomized stimuli of 35 and 43 to 49°C for a total of 32 stimuli. In order to identify different pain phenotypes, we employed a data-driven approach using a hierarchical cluster analysis of normalized pain intensity and unpleasantness ratings. A scree plot indicated that participants could be optimally divided into three broad clusters based on their pain ratings. These different phenotypes could be described as insensitive, moderately sensitive, and highly sensitive. A regression analysis was conducted for each cluster to calculate the stimulus response curves for each group according to Steven's Power Law. In all three clusters, pain unpleasantness stimulus response curves were characterized by steeper slopes than pain intensity stimulus response curves. The highly sensitive cluster exhibited a greater y-intercept and shallower slope for both intensity and unpleasantness stimulus response curves in relation to the other two groups. These differences in stimulus response curves could potentially support greater discriminability of small differences in noxious stimulus intensity in the highly sensitive cluster. Repeated measures analysis of variance confirmed that the highly sensitive cluster discriminated noxious stimuli of 1°C differences at lower stimulus intensities than other clusters. As such, these preliminary findings suggest that rating biases are not the primary source of observed individual differences in pain sensitivity. This research was supported by NIH NS085391.

Different functional domains measured by cocaine self-administration under the progressive-ratio and punishment schedules in male Wistar rats.

Current diagnosis of drug addiction like other mental disorders is based on clinical symptoms not on neural pathophysiology and consequently, does not provide useful information on the underlying pathophysiology and may impede the efforts to identify the underlying mechanisms. Identifying the functional deficits that are relevant to addiction and can be traced to the neural systems will greatly facilitate our understanding of the heterogeneity of the condition and improve future diagnosis and treatment. Cocaine addiction is characterized by the continued use despite the dire consequences, and the deficit in inhibitory control may play a key role in this process. This study aimed to develop a paradigm to measure the punishment-induced inhibitory regulation of reward-seeking behavior. Rats were first trained to self-administer sucrose pellets under a chained schedule and then the breaking points (BPs) under the progressive-ratio schedule, and the intensity-response effects of footshock punishment on sucrose SA were measured. Subsequently, the rats went on to self-administer intravenous cocaine, and the BPs and the punishment intensity-response effects were similarly determined. The areas under the punishment intensity-response curves (AUCs) were calculated and used as an indicator of the sensitivity of the inhibitory system. The BPs for cocaine were not correlated with the AUCs. Furthermore, the change in the BPs for cocaine induced by changing cocaine dose did not predict the change in the AUCs. The intensity-response effects of punishment can be used to measure the function or sensitivity of the inhibitory system independent of the motivational state.