Natural history of MRI brain volumes in patients with neuronal ceroid lipofuscinosis 3: a sensitive imaging biomarker.

PURPOSE: Grey matter (GM) atrophy due to neuronal loss is a striking feature of patients with CLN3 disease. A precise and quantitative description of disease progression is needed in order to establish an evaluation tool for current and future experimental treatments. In order to develop a quantitative marker to measure brain volume outcome, we analysed the longitudinal volumetric development of GM, white matter (WM) and lateral ventricles and correlated those with the clinical course. METHODS: One hundred twenty-two MRI scans of 35 patients (21 females; 14 males; age 15.3 ± 4.8 years) with genetically confirmed CLN3 disease were performed. A three-dimensional T1-weighted sequence was acquired with whole brain coverage. Volumetric segmentation of the brain was performed with the FreeSurfer image analysis suite. The clinical severity was assessed by the Hamburg jNCL score, a disease-specific scoring system. RESULTS: The volumes of supratentorial cortical GM and supratentorial WM, cerebellar GM, basal ganglia/thalamus and hippocampus significantly (r = - 0.86 to - 0.69, p < 0.0001) decreased with age, while the lateral ventricle volume increased (r = 0.68, p < 0.0001). Supratentorial WM volume correlated poorer with age (r = - 0.56, p = 0.0001). Supratentorial cortical GM volume showed the steepest (4.6% (± 0.2%)) and most uniform decrease with strongest correlation with age (r = - 0.86, p < 0.0001). In addition, a strong correlation with disease specific clinical scoring existed for the supratentorial cortical GM volume (r = 0.85, p = < 0.0001). CONCLUSION: Supratentorial cortical GM volume is a sensitive parameter for assessment of disease progression even in early and late disease stages and represents a potential reliable outcome measure for evaluation of experimental therapies.

Simultaneous multi-slice accelerated diffusion-weighted imaging with higher spatial resolution for patients with liver metastases from neuroendocrine tumours.

AIM: To evaluate the imaging characteristics of simultaneous multi-slice (SMS) accelerated diffusion-weighted imaging (DWI) with decreased section thickness, with and without motion correction, in comparison to conventional DWI (cDWI) for the detection of lesions in patients with neuroendocrine tumour (NET) liver metastases. MATERIALS AND METHODS: Fifteen patients with NET liver metastases underwent cDWI (section thickness [SL]=4 mm) and SMS-DWI (SL=2 mm). Non-linear motion-corrected (Moco)-SMS-DWI was generated in addition to the original series. Qualitative imaging characteristics (five-point Likert scale), the number of high signal lesions, and the detectability and delineation of lesions were evaluated and compared using the Friedman and the Dunn-Bonferroni tests. The test-retest variability (TRV) of the cDWI and SMS-DWI techniques was investigated among 11 healthy volunteers who underwent cDWI (SL=4 mm) and SMS-DWI (SL=4 mm) twice. The Friedman and the Dunn-Bonferroni post-hoc tests were used to compare the mean apparent diffusion coefficient (ADC) and the TRV in different liver regions between the three series. RESULTS: Moco-SMS-DWI demonstrated significantly superior overall image quality (p<0.001) with significantly fewer artefacts (p=0.003) than cDWI. The number of lesions detected by cDWI, SMS-DWI, and Moco-SMS-DWI were 348, 504, and 523, respectively. The detectability and delineation of the lesions and the ADC values were significantly higher on the SMS-DWI and Moco-SMS-DWI images than on the cDWI images (all p<0.001). Moco-SMS-DWI showed significantly higher TRV than cDWI in regions near the liver edge (p=0.018). CONCLUSIONS: SMS-DWI achieves higher spatial resolution than cDWI within the same acquisition time, detects more lesions, and provides better lesion delineation. By applying motion correction, the TRV of DWI could be enhanced in regions near the liver edge.

Dynamic contrast enhanced MRI of the head and neck region using a VIBE sequence with Cartesian undersampling and compressed sensing.

OBJECTIVES: Compressed sensing allows for image reconstruction from sparsely sampled k-space data, which is particularly useful in dynamic contrast enhanced MRI (DCE-MRI). The aim of the study was to assess the diagnostic value of a volume-interpolated 3D T1-weighted spoiled gradient-echo sequence with variable density Cartesian undersampling and compressed sensing (CS) for head and neck MRI. METHODS: Seventy-one patients with clinical indications for head and neck MRI were included in this study. DCE-MRI was performed at 3 Tesla magnet using CS-VIBE (variable density undersampling, temporal resolution 3.4 s, slice thickness 1 mm). Image quality was compared to standard Cartesian VIBE. Three experienced readers independently evaluated image quality and lesion conspicuity on a 5-point Likert scale and determined the DCE-derived time intensity curve (TIC) types. RESULTS: CS-VIBE demonstrated higher image quality scores compared to standard VIBE with respect to overall image quality (4.3 ± 0.6 vs. 4.2 ± 0.7, p = 0.682), vessel contour (4.6 ± 0.4 vs. 4.4 ± 0.6, p < 0.001), muscle contour (4.4 ± 0.5 vs. 4.5 ± 0.6, p = 0.302), lesion conspicuity (4.5 ± 0.7 vs. 4.3 ± 0.9, p = 0.024) and showed improved fat saturation (4.8 ± 0.3 vs. 3.8 ± 0.4, p < 0.001) and movement artifacts were significantly reduced (4.6 ± 0.6 vs. 3.7 ± 0.7, p < 0.001). Standard VIBE outperformed CS-VIBE in the delineation of pharyngeal mucosa (4.2 ± 0.5 vs. 4.6 ± 0.6, p < 0.001). Lesion size in cases where a focal lesion was identified was similar for all readers for CS-VIBE and standard VIBE (p = 0.101). TIC curve assessment showed good interobserver agreement (k=0.717). CONCLUSION: CS-VIBE with variable density Cartesian undersampling allows for DCE-MRI of the head and neck region with diagnostic, high image quality and high temporal resolution.

Improved diffusion-weighted imaging of the prostate: Comparison of readout-segmented and zoomed single-shot imaging.

OBJECTIVES: Diffusion weighted imaging (DWI) is the most important sequence for detection and grading prostate cancer (PCa), but it is considerably prone to artifacts. New approaches like zoomed single-shot imaging (z-EPI) with advanced image processing or multi-shot readout segmentation (rs-EPI) try to improve DWI quality. This study evaluates objective and subjective image quality (IQ) of rs-EPI and z-EPI with and without advanced processing. MATERIALS AND METHODS: Fifty-six consecutive patients (67 ± 8 years; median PSA 8.3 ng/ml) with mp-MRI performed at 3 Tesla between February and October 2019 and subsequently verified PCa by targeted plus systematic MRI/US-fusion biopsy were included in this retrospective single center cohort study. Rs-EPI and z-EPI were prospectively acquired in every patient. Signal intensities (SI) of PCa and benign tissue in ADC, b1000, and calculated high b-value images were analyzed. Endpoints were signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), PCa contrast intensity (CI), and subjective IQ on a 5-point scale evaluated by three blinded readers. Wilcoxon signed rank test, Friedman test and Cohen's kappa coefficient was calculated. RESULTS: SNR, CNR, and PCa CI of z-EPI with and without advanced processing was superior to rs-EPI (p < 0.01), whereas no significant differences were observed between z-EPI with and without advanced processing. Subjective IQ was significantly higher for z-EPI with advanced processing compared rs-EPI for ADC, b1000, and calculated high b-values (p < 0.01). Compared to z-EPI without advanced processing, z-EPI with advanced processing was superior for ADC and calculated high b-values (p < 0.01), but no significant differences were shown for b1000 images. CONCLUSIONS: Z-EPI with and without advanced processing was superior to rs-EPI regarding objective imaging parameters and z-EPI with advanced processing was superior to rs-EPI regarding subjective imaging parameters for the detection of PCa.

Functional relaxation and guided imagery as complementary therapy in asthma: a randomized controlled clinical trial.

BACKGROUND: Asthma is a frequently disabling and almost invariably distressing disease that has a high overall prevalence. Although relaxation techniques and hypnotherapeutic interventions have proven their effectiveness in numerous trials, relaxation therapies are still not recommended in treatment guidelines due to a lack of methodological quality in many of the trials. Therefore, this study aims to investigate the efficacy of the brief relaxation technique of functional relaxation (FR) and guided imagery (GI) in adult asthmatics in a randomized controlled trial. METHODS: 64 patients with extrinsic bronchial asthma were treated over a 4-week period and assessed at baseline, after treatment and after 4 months, for follow-up. 16 patients completed FR, 14 GI, 15 both FR and GI (FR/GI) and 13 received a placebo relaxation technique as the control intervention (CI). The forced expiratory volume in the first second (FEV(1)) as well as the specific airway resistance (sR(aw)) were employed as primary outcome measures. RESULTS: Participation in FR, GI and FR/GI led to increases in FEV(1) (% predicted) of 7.6 +/- 13.2, 3.3 +/- 9.8, and 8.3 +/- 21.0, respectively, as compared to -1.8 +/- 11.1 in the CI group at the end of the therapy. After follow-up, the increases in FEV(1) were 6.9 +/- 10.3 in the FR group, 4.4 +/- 7.3 in the GI and 4.5 +/- 8.1 in the FR/GI, compared to -2.8 +/- 9.2 in the CI. Improvements in sR(aw) (% predicted) were in keeping with the changes in FEV(1) in all groups. CONCLUSIONS: Our study confirms a positive effect of FR on respiratory parameters and suggests a clinically relevant long-term benefit from FR as a nonpharmacological and complementary therapy treatment option.

A Comparison between 6-point Dixon MRI and MR Spectroscopy to Quantify Muscle Fat in the Thigh of Subjects with Sarcopenia.

BACKGROUND: Changes in muscle fat composition as for example observed in sarcopenia, affect physical performance and muscular function, like strength and power. OBJECTIVES: The purpose of this study was to compare 6-point Dixon magnetic resonance imaging and multi-echo magnetic resonance spectroscopy sequences to quantify muscle fat. Setting, participants and measurements: Two groups were recruited (G1: 23 healthy young men (28 ± 4 years), G2: 56 men with sarcopenia (80 ± 5 years)). Proton density fat fraction was measured with a 6-point product and a 6-point prototype Dixon sequence in the left thigh muscle and with a high-speed multi-echo T2*-corrected H1 magnetic resonance spectroscopy sequence within the semitendinosus muscle of the left thigh. To evaluate the comparability among the different methods, Bland-Altman and linear regression analyses of the proton density fat fraction results were performed. RESULTS: Mean differences ± 1.96 * standard deviation between spectroscopy and 6pt Dixon sequences were 1.9 ± 3.3% and 1.5 ± 3.6% for the product and prototype sequences, respectively. High correlations were measured between the proton density fat fraction results of the 6-point Dixon sequences and spectroscopy (R = 0.95 for the product sequence and R = 0.97 for the prototype sequence). CONCLUSIONS: Dixon imaging and spectroscopy sequences show comparable accuracy for fat measurements in the thigh. Spectroscopy is a local measurement, whereas Dixon sequences provide maps of the fat distribution. The high correlations of the 6-point Dixon sequences with spectroscopy support their clinical use. They provide higher spatial resolution than spectroscopy, but are not suitable for a more complicated spectral analysis to separate extra- and intramyocellular lipids.

Lamotrigine treatment of aggression in female borderline patients, Part II: an 18-month follow-up.

Borderline patients often display pathological aggression. We previously tested lamotrigine, an anti-convulsant, in therapy for aggression in women with borderline personality disorder (BPD) (J Psychopharmacol 2005; 19: 287-291), and found significant changes on most scales of the State-Trait Anger Expression Inventory (STAXI) after eight weeks. To assess the longer-term efficacy of lamotrigine in therapy for aggression in women with BPD, this 18-month follow-up observation was carried out, in which patients (treated with lamotrigine: n = 18; former placebo group: n = 9) were tested every six months. According to the intent-to-treat principle, significant changes on all scales of the STAXI were observed in the lamotrigine-treated subjects. All subjects tolerated lamotrigine relatively well. Lamotrigine appears to be an effective and relatively safe agent in the longer-term treatment of aggression in women with BPD.

Cabergoline treatment in men with psychogenic erectile dysfunction: a randomized, double-blind, placebo-controlled study.

The effectiveness of cabergoline in 50 men with psychogenic erectile dysfunction was investigated in a 4-month, randomized, placebo-controlled, double-blind study with validated psychological tests, and prolactin, follicle-stimulating hormone, luteinizing hormone and testosterone serum levels. Cabergoline treatment was well-tolerated and resulted in normalization of hormone levels in most cases. In the cabergoline-treated group, significant interactions between prolactin and testosterone serum concentrations were observed. Erectile function improved significantly. Sexual desire, orgasmic function, and the patient's and his partner's sexual satisfaction were also enhanced. Cabergoline may be an effective and safe alternative agent for men with psychogenic ED.

Volumetric Description of Brain Atrophy in Neuronal Ceroid Lipofuscinosis 2: Supratentorial Gray Matter Shows Uniform Disease Progression.

BACKGROUND AND PURPOSE: Experimental therapies for ceroid lipofuscinosis, neuronal, 2 (CLN2), a genetic disorder of childhood associated with progressive brain atrophy, are currently being developed. Because quantitative descriptions of the natural course of brain volume loss are needed to evaluate novel therapies, we performed MR imaging volumetry of patients with CLN2 to identify a suitable MR imaging marker of disease progression. MATERIALS AND METHODS: Thirteen patients (8 females, 5 males) were recruited from a prospective natural disease cohort of patients with neuronal ceroid lipofuscinosis. Repeated MR imaging volumetric analysis (29 datasets) was performed by using the FreeSurfer Software Suite. Follow-up time ranged from 8 months to 5.3 years. MR imaging-segmented brain volumes were correlated to patient age and clinical scores. RESULTS: Segmented brain volumes correlated significantly with patient age (lateral ventricles, r = 0.606, P = .001; supratentorial cortical GM, r = -0.913, P < .001; supratentorial WM, r = -0.865, P < .001; basal ganglia/thalamus, r = -0.832, P < .001; cerebellar GM, r = -0.659, P < .001; cerebellar WM, r = -0.830, P < .001) and clinical scores (lateral ventricles, r = -0.692, P < .001; supratentorial cortical GM, r = 0.862, P < .001; supratentorial WM, r = 0.735, P < .001; basal ganglia/thalamus, r = 0.758, P < .001; cerebellar GM, r = 0.609, P = .001; cerebellar WM, r = 0.638, P < .001). Notably, supratentorial cortical GM showed a uniform decline across the patient cohort. During late stages of the disease when the clinical score was zero, segmented brain volumes still correlated with patient age; this finding suggests that MR imaging volumetry allows quantitative assessment of disease progression at stages when it cannot be detected by clinical assessment alone. CONCLUSIONS: Automated MR imaging volumetry, as a nonsubjective and highly sensitive tool, is feasible in CLN2 disease and provides a quantitative basis to evaluate novel experimental therapies.

Novel morphological macular findings in juvenile CLN3 disease.

AIMS: Juvenile CLN3 disease, one of the most common forms of a group of lysosomal storage diseases called neuronal ceroid lipofuscinoses (NCLs), is a progressive neurodegenerative disorder with initial visual deterioration. The objective of this study was to analyse the retinal phenotype of patients with CLN3 disease with the help of recent ophthalmic imaging modalities to distinguish CLN3 disease from other inherited retinal dystrophies. METHODS: Patients underwent ophthalmic evaluations, including anterior and posterior segment examinations, optical coherence tomography, fundus autofluorescence, near infrared imaging and fundus photography. Patients were also assessed according to the Hamburg juvenile NCL (JNCL) score. Each ophthalmic finding was assessed by three independent examiners and assigned to a clinical severity score. RESULTS: 22 eyes of 11 patients were included. The mean age at examination was 14.4 years (range 11.8-26.4 years), with an average age at initial diagnosis of 8 years (range 4.5-11 years). The mean Hamburg JNCL score was 7.3 (range 0-13). All patients showed a specific macular striation pattern on optical coherence tomography that was independent of age and progression of the disease. Other previously described retinal features of CLN3 disease were classified into four severity grades. CONCLUSIONS: This study represents the first prospective observational case series documenting retinal abnormalities in CLN3 disease with the aid of the spectral domain optical coherence tomography. The major finding was a characteristic, striated macular pattern in all patients studied. Particularly in early disease cases, macular striae can potentially help to discriminate CLN3 disease from other inherited forms of retinitis pigmentosa.

Arg123-Tyr166 domain of human ApoA-I is critical for HDL-mediated inhibition of macrophage homing and early atherosclerosis in mice.

Atherosclerosis was studied in apolipoprotein E (apoE) knockout mice expressing human apolipoprotein A-I (apoA-I) or an apoA-I/apolipoprotein A-II (apoA-II) chimera in which the Arg123-Tyr166 central domain of apoA-I was substituted with the Ser12-Ala75 segment of apoA-II. High density lipoprotein (HDL) cholesterol levels were identical in apoA-I and apoA-I/apoA-II mice, but at 4 months, plaques were 2.7-fold larger in the aortic root of the apoA-I/apoA-II mice (P<0.01). The macrophage-to-smooth muscle cell ratio of lesions was 2.1-fold higher in apo-I/apoA-II mice than in apoA-I mice (P<0.01). This was due to a 2.7-fold higher (P<0.001) in vivo macrophage homing in the aortic root of apoA-I/apoA-II mice. Plasma platelet-activating factor acetyl hydrolase activity was lower (P<0.01) in apoA-I/apoA-II mice, resulting in increased oxidative stress, as evidenced by the higher titer of antibodies against oxidized low density lipoprotein (P<0.01). Increased oxidative stress resulted in increased stimulation of ex vivo macrophage adhesion by apoA-I/apoA-II beta-very low density lipoprotein and decreased inhibition of beta-very low density lipoprotein-induced adhesion by HDL from apoA-I/apoA-II mice. The cellular cholesterol efflux capacity of HDL from apoA-I/apoA-II mice was very similar to that of apoA-I mice. Thus, the Arg123-Tyr166 central domain of apoA-I is critical for reducing oxidative stress, macrophage homing, and early atherosclerosis in apoE knockout mice independent of its role in HDL production and cholesterol efflux.

Sustainable use of marine resources: cultivation of sponges.

Among all metazoan phyla, sponges are known to produce the largest number of bioactive compounds, some of them metabolites with human therapeutic value. Therefore, an increasing interest in basic cell biology research up to biochemical engineering can be observed aiming at the production of sponge metabolites under completely controlled conditions. One major obstacle is the limited availability of larger quantities of defined sponge material--the so-called supply problem. In this chapter, different approaches used so far for producing sponge biomass by in situ aquaculture as well as some significant progress in the maintenance of sponges in aquaria are reviewed. These approaches are mainly based on old methods for producing commercial bath sponges as well as on experience in maintaining sponges in public aquaria and on the usage of artificial substrates for a natural-like colonization structure. In recent years, great efforts have been made to set up in vitro culture systems for the cultivation of sponge cells. One of the major advantages of cell cultures is the possibility to control and manipulate the cultivation conditions depending on the sponge species and the target metabolite. Up to now, monolayer cultures of dissociated sponge cells have been shown in a few cases to produce the desired product. However, to date, no continuously growing sponge cell line has been established. Organotypic culture systems, which maintain or mimic the natural tissue structure, have been developed in recent years and demonstrate a promising way towards the biotechnology of sponges. Successful attempts to produce sponge metabolites using the three-dimensional growing primmorphs are given. The use of sponge fragments, another three-dimensional approach, has reappeared and has also been successfully used as an in vitro approach as well as for the biotechnological production of boreal sponge tissue.

Primmorphs generated from dissociated cells of the sponge Suberites domuncula: a model system for studies of cell proliferation and cell death.

Sponges (Porifera) represent the lowest metazoan phylum; they have been shown to be provided with the characteristic metazoan structural and functional molecules. One autapomorphic character of sponges is the presence of high levels of telomerase activity in all cells (or almost all cells, including somatic cells). In spite of this fact previous attempts to cultivate sponge cells remained unsuccessful. It was found that dissociated sponge cells do not replicate DNA and lose their telomerase activity. In addition, no nutrients or metabolites have been detected that would stimulate sponge cells to divide. In the present study we report the culture conditions required for the formation of multicellular aggregates from dissociated single cells of Suberites domuncula, termed primmorphs. These primmorphs are formed in seawater without addition of further supplements, and have an organised tissue-like structure; they have been cultured for more than 5 months. Cross-sections revealed a distinct external layer covered by a continuous pinacoderm, and a central zone composed primarily of spherulous cells. After their association into primmorphs, the cells turn from the telomerase-negative state into the telomerase-positive state; a telomerase level of 4.7 total product generated (TPG) units/5 x 10(3) cell equivalents has been determined. Moreover, a major fraction of the cells in the primmorphs undergoes DNA synthesis and hence has the capacity to grow. Applying the BrdU-labelling and detection assay it is demonstrated that up to 33.8% of the cells in the primmorphs are labelled with BrdU after an incubation period of 12 h. It is proposed that the primmorph system described here is a powerful novel model system to study basic mechanisms of cell proliferation and cell interaction, as well as of morphogenesis, ageing and apoptosis.

Comparative studies on two potential methods for the biotechnological production of sponge biomass.

The production of marine sponge biomass is one of the main outstanding goals of marine biotechnology. Due to the increased number of sponge secondary metabolites of economical value the interest in sponge cultivation increased over the last years, too. Therefore, we examined cultivation properties of 11 Mediterranean sponge species. Two methodologies were tested: functional fragment culture and multicell reaggregate culture. The in vitro cultivation of sponge fragments without further dissociation and reaggregation is a method formerly not reported. Reaggregates and functional fragments are promising attempts for culture system development. A broad spectrum of reaggregation properties was found among the species tested. In three species multicell aggregate cultures could be maintained for several months: Petrosia ficiformis, Suberites domuncula and Acanthella acuta. Our results indicate that cellular aggregates or fragments of sponges can be valuable tools in the development of methods for biotechnological production of sponge biomass. Further focus on nutritional demands and the biochemical status of the cells in these kind of cellular associations are needed in order to obtain functional aggregates and fragments.

Fixed-ratio size as a determinant of the development of tolerance to morphine.

The acute and chronic effects of morphine were examined in pigeons exposed to a multiple schedule with fixed-ratio 5, 25, and 125 components. Acute exposure to morphine (0.56-10.0 mg/kg) resulted in rate reductions under each component when the dose was 1 mg/kg or higher. With chronic exposure to 5.6 mg/kg, tolerance to the rate-reducing effects of morphine was evident under each fixed-ratio component. The development of tolerance was determined to some extent by fixed-ratio size, a result similar to earlier findings with cocaine.

Fixed-ratio size as a determinant of tolerance to cocaine: is relative or absolute size important?

Six studies, examining five drugs in three species, have demonstrated that tolerance development is impaired under relatively long fixed-ratio (FR) schedules compared with relatively short FR schedules. One such study demonstrated that substantial tolerance to the rate-reducing effects of cocaine in pigeons developed under the FR 5 and 25 components of a multiple schedule of food delivery, but little or no tolerance developed under the FR 125 component. The present study examined the acute and chronic effects of cocaine in three groups of pigeons. One group was exposed to a simple FR 5 schedule of food delivery, a second to a simple FR 125 schedule of food delivery, and a third to a simple FR 125 schedule that alternated across sessions with a multiple FR 125 FR 250 schedule. When administered acutely, cocaine (1-10mg/kg) produced dose-dependent rate decreases under all schedules. With chronic exposure to 5.56mg/kg cocaine, tolerance clearly developed under the FR 5 schedule. Evidence of tolerance under the FR 125 schedule was equivocal, but strongest when that schedule alternated with an FR 250 component under a multiple schedule arrangement. There was no consistent evidence of tolerance under the FR 250 component. These results suggest that, although the development of tolerance under an FR schedule may be affected by exposure to a longer schedule, tolerance to cocaine does not develop readily under "long" FR schedules, regardless of the context in which they appear.

The effects of phenobarbital on responding under delayed-matching-to-sample procedures with differential and nondifferential outcomes.

Pigeons were exposed to delayed-matching-to-sample procedures in which food or a flash of the feeder light followed correct responses. When these consequences were correlated with a particular stimulus (e.g., food followed matching responses to red and a flash of the feeder light followed matching responses to green), accuracy was significantly higher (i.e., stimulus control was greater) than when discriminative stimuli and consequences were not correlated. Acute administrations of phenobarbital (10-40 mg/kg) produced similar effects regardless of whether or not differential outcomes were arranged for correct responses to a particular stimulus. At doses of 30 and 40 mg/kg, phenobarbital significantly decreased accuracy under both variations of the delayed-matching-to-sample procedure. Given these results, it appears that degree of stimulus control in the absence of drug did not modulate drug effects in the present study.

Effects of d-amphetamine and ethosuximide on responding under delayed-matching-to-sample procedures with differential and nondifferential outcomes.

Pigeons were exposed to delayed-matching-to-sample (DMTS) procedures in which food or a flash of the feeder light followed correct responses. When these consequences were correlated with a particular stimulus (e.g., food followed matching responses to red and a flash of the feeder light followed matching responses to green), accuracy was higher (i.e., stimulus control was greater) than when discriminative stimuli and consequences were not correlated. Although stimulus control in the absence of drug appeared to be weaker under the uncorrelated procedure, neither d-amphetamine (0.5-3.0 mg/kg) in Experiment 1 nor ethosuximide (40-160 mg/kg) in Experiment 2 disrupted accuracy to a greater extent under that procedure. These results, like those of a prior investigation, suggest that drug effects are similar under DMTS procedures regardless of whether correlated or uncorrelated outcomes are arranged.