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PubMedDate not supplied

Performance on the Hooper Visual Organizational Test in patients diagnosed with subcortical vascular dementia: relation to naming performance.

OBJECTIVE: To examine the performance of individuals with vascular dementia (VaD) on the Hooper Visual Organization Test (HVOT) and to determine the influence of naming on HVOT performance in this population. BACKGROUND: The HVOT is commonly administered to assess visuospatial perception among neurologic patients, but the test requires verbal identification of stimuli as well as spatial ability. Previous studies have examined the influence of naming on the HVOT, but the issue has not been systematically addressed in individuals with subcortical VaD. METHOD: Individuals with a diagnosis of VaD were administered the HVOT, three additional measures of visuospatial function (Block Design and Picture Completion subtests of the Wechsler Adult Intelligence Scale-Revised, Rey-Osterrieth Complex Figure Test copy trial), and the Boston Naming Test (BNT). RESULTS: On average, the VaD patients performed poorly compared with normative data on each of the cognitive measures, with the most pronounced deficit evident on the BNT. Regression analyses revealed that more than 60% of the variance in performance on the HVOT was accounted for by performance on the Block Design subtest of the Wechsler Adult Intelligence Scale-Revised; performance on the BNT did not contribute significantly. CONCLUSIONS: The results suggest that VaD patients perform below expectations on the HVOT and that the measure is robust to naming deficits in this population.

Brain↗
PubMed1996

Safety and efficacy of doxazosin in benign prostatic hyperplasia: a pooled analysis of three double-blind, placebo-controlled studies.

OBJECTIVES: To present the results of a pooled analysis of three double-blind, placebo-controlled studies of doxazosin in benign prostatic hyperplasia (BPH). Heterogeneous symptom and bother score data collected using different symptom indices were transformed to enable a comparison of the data and to conduct a pooled, in-depth analysis. METHODS: Urinary flow rates, and symptom and bother score data were shown by analysis of covariance methods to give consistent estimates of the efficacy of doxazosin across different studies, thus confirming the validity of pooling the results. Prior to analysis, symptom and bother score data were transformed so that all scales started from zero (least symptoms or bother) and were expressed as a percentage of the maximum score. RESULTS: Doxazosin produced a significantly greater improvement than placebo in peak urinary flow rate (P = 0.0017), symptom severity (P < 0.0001), and bother caused by symptoms (P < 0.0001). Stratification showed that a greater improvement was obtained during doxazosin treatment by those with more severe symptoms at baseline (P = 0.0001). Stratification by age showed that age did not affect the capacity to benefit from treatment. Analysis of the pooled peak flow-rate data showed that doxazosin produced a consistently greater increase in flow compared with placebo. Doxazosin was well tolerated, with 10% of patients having withdrawn due to adverse events versus 4% with placebo (P < 0.05). CONCLUSIONS: Doxazosin is well tolerated and effective in the treatment of BPH. Pooling of data has enabled more extensive and robust conclusions to be drawn than was possible for each one of the individual three studies.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Evaluation of antitussive agents in man.

Methodology to evaluate the efficacy of antitussive drugs rely largely on subjective methods and cough counts. There are few studies in cough due to natural disease especially using objective techniques. This paper presents data from a series of randomized, double blind, placebo controlled clinical trials in cough due to both chronic bronchopulmonary disease and acute upper respiratory tract infections. In these studies, cough was quantified using a standardized and validated computerized system for the acquisition and multidimensional analysis of the cough sound. Key objective parameters like cough counts, intensity, latency and total effort expended were studied. Guaiphenesin and bromhexine showed significant expectorant effects in patients with productive cough due to chronic bronchopulmonary disease. Differences were observed in speed of action, and objective and subjective measures, that probably indicate differences in drug action. More recently, three studies evaluated the antitussive drug dextromethorphan in non-productive cough due to uncomplicated upper respiratory tract infections. Reproducible cough suppressant effects were demonstrated after a single 30 mg dose using objective measures of cough counts, latency and total effort. These results establish the sensitivity and robustness of the cough quantitation methodology in the objective evaluation of cough treatments.

Acute Disease↗
PubMed2000

Power of a score test for quantitative trait linkage analysis of relative pairs.

The score test of Dudoit and Speed [(2000) Biostatistics 1:1-26] to detect linkage between a trait locus and a marker locus, using identity by descent data on sib pairs, is extended to other types of relative pairs (grandparent/grandchild, avuncular, and half-sib relationships). The test is based on the likelihood of the recombination fraction theta between trait and marker loci, conditional on phenotypes of the relatives. We present results of simulation studies characterizing power and robustness properties of this linkage score test, and compare the power of the score test to that of the classical and modified Haseman-Elston tests. The score test has considerable power, particularly under sampling schemes where selection is on double probands. Use of a generic additive model [Goldstein et al., submitted] with allele frequency p = 0.2, heritability H = 0.3, and a moderate residual correlation of rho = 0.2 resulted in a very good overall performance across a wide range of trait-generating models.

Computer Simulation↗
PubMed2005

A system for inducible gene expression in retinal ganglion cells.

PURPOSE: To develop a system for inducible gene expression in retinal ganglion cells, Thy1 and ckit promoters were used to direct expression of a second-generation reverse tetracycline transactivator (rtTA2S-M2). METHODS: Transgenic mice were generated that harbor rtTA2S-M2 under the control of either the Thy1 or ckit promoter. These animals were crossed with mice transgenic for the LacZ gene downstream of a cassette of tet operator (TRE) binding sites. Induction of the LacZ reporter gene in vivo after either oral or subcutaneous doxycycline administration and in vitro in cultured retinal cells was assessed. To examine induction of a secreted protein, expression of pigment epithelium-derived factor (PEDF) in mice harboring Thy1-rtTA and TRE-PEDF constructs was quantified. RESULTS: Five of seven Thy1-rtTA lines showed induction with subcutaneous doxycycline: maximum induction in one line (Thy1-C), moderate in one line (Thy1-F), and minimal in three lines. There was no detectable retinal LacZ expression in the ckit-rtTA lines, despite expression of the ckit-rtTA transgene at the RNA level. In Thy1-rtTA lines, LacZ reporter expression as measured by X-gal staining was evenly dispersed throughout all quadrants of the retina, present in a subpopulation of retinal ganglion cell (RGC) bodies, RGC axons projecting through the retina and optic nerve, and some cells in the inner nuclear layer. Immunostaining for beta-galactosidase demonstrated more uniform expression in RGCs and cells of the inner aspect of the inner nuclear layer, which, by double staining with anti-beta-galactosidase and anti-calretinin antibodies, were consistent with amacrine cells. More than 95% of Thy-1 antigen-positive cells in the retina expressed the induced transgene. Subcutaneous doxycycline resulted in a more robust induction of LacZ than did oral administration. In vitro, the number of cells induced in culture increased in a dose-dependent manner, with maximum expression at 10 microg/mL at a level 3.4-fold over background. Thy1-rtTA/TRE-PEDF mice treated with doxycycline had 1000-fold induction in their retinal PEDF expression in comparison with nontransgenic mice and 600-fold induction over noninduced Thy1-rtTA/TRE-PEDF mice. CONCLUSIONS: A transgenic system for inducible RGC expression has been developed that demonstrates minimal leakiness and significant induction with doxycycline. This system will be useful for several applications.

Animals↗
PubMed2005

Shear-controlled single-step mouse embryonic stem cell expansion and embryoid body-based differentiation.

To facilitate the exploitation of embryonic stem cells (ESCs) and ESC-derived cells, scale-up of cell production and optimization of culture conditions are necessary. Conventional ESC culture methods are impractical for large-scale cell production and lack robust microenvironmental control. We developed two stirred-suspension culture systems for the propagation of undifferentiated ESCs--microcarrier and aggregate cultures--and compared them with tissue-culture flask and Petri dish controls. ESCs cultured on glass microcarriers had population doubling times (approximately 14-17 hours) comparable to tissue-culture flask controls. ESC growth could be elicited in shear-controlled stirred-suspension culture, with population doubling times ranging between 24 and 39 hours at 100 rpm impeller speed. Upon removal of leukemia inhibitory factor, the size-controlled ESC aggregates developed into embryoid bodies (EBs) capable of multilineage differentiation. A comprehensive analysis of ESC developmental potential, including flow cytometry for Oct-4, SSEA-1, and E-cadherinprotein expression, reverse transcription-polymerase chain reaction for Flk-1, HNF3-beta, MHC, and Sox-1 gene expression, and EB differentiation analysis, demonstrated that the suspension-cultured ESCs retained the developmental potential of the starting cell population. Analysis of E-cadherin-/- and E-cadherin+/- cells using both systems provided insight into the mechanisms behind the role of cell aggregation control, which is fundamental to these observations. These cell-culture tools should prove useful for both the production of ESCs and ESC-derived cells and for investigations into adhesion, survival, and differentiation phenomena during ESC propagation and differentiation.

Animals↗
PubMed1999

Effects of alprazolam on the acoustic startle response in humans.

In the present study, we assessed the effects of the potent benzodiazepine alprazolam on the human acoustic startle response in healthy volunteers. Eight undergraduate students received single oral doses of placebo and alprazolam 2 mg on 2 separate days, according to a double-blind balanced crossover design. Electromyographic activity of the orbicularis oculi muscle was recorded 5, 7 and 11 h after drug administration. At each recording time, subjects received 21 acoustic stimuli (1 KHz, 116 dB, 50 ms duration) separated by variable intervals (8-30 s, mean 16.5 s). Consistent with previous results obtained for diazepam in humans, alprazolam significantly reduced the amplitude of the startle reflex. A patent increase in onset latency was also observed, this being a novel effect not previously described for benzodiazepines in human studies. Both effects were maximum at 5 h after dosing, the startle response experiencing a recovery as the drug disappeared from systemic circulation. These results indicate a potent inhibitory effect of alprazolam on baseline startle at the dose used, with a robust time-dependent recovery of initial values effectively counteracting between-session habituation.

Adult↗
PubMed2005

Lack of behavioural effects after acute tyrosine depletion in healthy volunteers.

Acute dietary tyrosine depletion has previously been shown to reduce dopamine neurotransmission in both animals and humans. In this study, we investigated the effects of brain dopamine depletion, through acute tyrosine and phenylalanine depletion, on plasma prolactin, mood and neuropsychological function in 12 normal subjects. In a randomized, double-blind, cross-over design, subjects received two amino-acid drinks separated by a week, a nutritionally balanced mixture (Bal) and on the other occasion a tyrosine and phenylalanine deficient mixture (TP-). The plasma ratio of tyrosine and phenylalanine to the other large neutral amino acids decreased significantly on the TP- occasion (-78.7%, p < 0.0001) and there was an increase in plasma prolactin concentration relative to the balanced drink in the seven subjects for whom results were available for both occasions (p < 0.02). Acute tyrosine depletion did not alter mood as measured by visual analogue scale ratings, and measures of memory, attention and behavioural inhibition were also unaffected. Our results are consistent with acute dietary tyrosine depletion causing a reduction in brain dopamine neurotransmission but raise questions about how robust or consistent the effects are on psychological function.

Adult↗
PubMed2000

Survival analysis for recurrent event data: an application to childhood infectious diseases.

Many extensions of survival models based on the Cox proportional hazards approach have been proposed to handle clustered or multiple event data. Of particular note are five Cox-based models for recurrent event data: Andersen and Gill (AG); Wei, Lin and Weissfeld (WLW); Prentice, Williams and Peterson, total time (PWP-CP) and gap time (PWP-GT); and Lee, Wei and Amato (LWA). Some authors have compared these models by observing differences that arise from fitting the models to real and simulated data. However, no attempt has been made to systematically identify the components of the models that are appropriate for recurrent event data. We propose a systematic way of characterizing such Cox-based models using four key components: risk intervals; baseline hazard; risk set, and correlation adjustment. From the definitions of risk interval and risk set there are conceptually seven such Cox-based models that are permissible, five of which are those previously identified. The two new variant models are termed the 'total time - restricted' (TT-R) and 'gap time - unrestricted' (GT-UR) models. The aim of the paper is to determine which models are appropriate for recurrent event data using the key components. The models are fitted to simulated data sets and to a data set of childhood recurrent infectious diseases. The LWA model is not appropriate for recurrent event data because it allows a subject to be at risk several times for the same event. The WLW model overestimates treatment effect and is not recommended. We conclude that PWP-GT and TT-R are useful models for analysing recurrent event data, providing answers to slightly different research questions. Further, applying a robust variance to any of these models does not adequately account for within-subject correlation.

Acute Disease↗
PubMed2004

Ditopic double pincer palladacycle catalyst for C-C coupling.

A ditopic palladacycle with SCS pincer coordination, L(PdCl)(2) (1), was isolated and structurally characterized and represents the first example of a transition metal complex with a polythioamide-based macrocycle. Preliminary studies of 1 in the catalytic coupling of 4-iodotoluene and styrene indicated it to be robust in the presence of oxygen and high temperatures, with high turnover numbers in relatively short times.

Journal Article↗
PubMed2006

DNA double-strand break repair: all's well that ends well.

Breaks in both DNA strands are a particularly dangerous threat to genome stability. At a DNA double-strand break (DSB), potentially lost sequence information cannot be recovered from the same DNA molecule. However, simple repair by joining two broken ends, though inherently error prone, is preferable to leaving ends broken and capable of causing genome rearrangements. To avoid DSB-induced genetic disinformation and disruption of vital processes, such as replication and transcription, cells possess robust mechanisms to repair DSBs. Because all breaks are not created equal, the particular repair mechanism used depends largely on what is possible and needed based on the structure of the broken DNA. We argue that although categorizing different DSB repair mechanisms along pathways and subpathways can be conceptually useful, in cells flexible and reversible interactions among DSB repair factors form a web from which a nonpredetermined path to repair for any number of different DNA breaks will emerge.

Animals↗
PubMed2006

Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial.

CONTEXT: The need for improved therapeutic agents that more quickly and effectively treat depression is critical. In a pilot study we evaluated the role of the cholinergic system in cognitive symptoms of depression and unexpectedly observed rapid reductions in depression severity following the administration of the antimuscarinic drug scopolamine hydrobromide (4 microg/kg intravenously) compared with placebo (P = .002). Subsequently a clinical trial was designed to assess more specifically the antidepressant efficacy of scopolamine. OBJECTIVE: To evaluate scopolamine as a potential antidepressant agent. DESIGN: Two studies were conducted: a double-blind, placebo-controlled, dose-finding study followed by a double-blind, placebo-controlled, crossover clinical trial. SETTING: The National Institute of Mental Health. Patients Currently depressed outpatients aged 18 to 50 years meeting DSM-IV criteria for recurrent major depressive disorder or bipolar disorder. Of 39 eligible patients, 19 were randomized and 18 completed the trial. INTERVENTIONS: Multiple sessions including intravenous infusions of placebo or scopolamine hydrobromide (4 microg/kg). Individuals were randomized to a placebo/scopolamine or scopolamine/placebo sequence (series of 3 placebo sessions and series of 3 scopolamine sessions). Sessions occurred 3 to 5 days apart. MAIN OUTCOME MEASURES: Psychiatric evaluations using the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale were performed to assess antidepressant and antianxiety responses to scopolamine. RESULTS: The placebo/scopolamine group showed no significant change during placebo infusion vs baseline; reductions in depression and anxiety rating scale scores (P<.001 for both) were observed after the administration of scopolamine compared with placebo. The scopolamine/placebo group also showed reductions in depression and anxiety rating scale scores (P<.001 for both) after the administration of scopolamine, relative to baseline, and these effects persisted as they received placebo. In both groups, improvement was significant at the first evaluation after scopolamine administration (P< or =.002). CONCLUSION: Rapid, robust antidepressant responses to the antimuscarinic scopolamine occurred in currently depressed patients who predominantly had poor prognoses.

Adult↗
PubMed2004

Calibration of echo-planar 2D-selective RF excitation pulses.

Echo-planar radiofrequency (RF) pulses (EPP) are increasingly being used for 2D-selective excitation in MRI. Pulse schemes of this kind are susceptible to eddy-current effects, timing imperfections, and anisotropy of the gradient system. As a consequence, practical EPP implementations have been restricted to robust fly-back strategies that use only every other leg of the echo-planar trajectory for RF transmission. The present work is dedicated to enabling forward-backward EPP with RF transmission during each k-space segment, hence doubling the pulses' time efficiency. This is accomplished by comprehensive pulse calibration based on preparatory measurements of the system imperfections, including potential gradient anisotropy. The effectiveness of the method is demonstrated in vitro and in vivo. By doubling the speed of k-space coverage, the proposed method enhances the potential of EPP for numerous applications. For example, motion-sensitive techniques benefit from shorter feasible echo times (TEs) and improved excitation profiles resulting from reduced in-pulse motion. In sequences with fast repetition, shorter EPP help reduce the overall scan duration. Alternatively, the higher time efficiency of forward-backward EPP can enhance their spatial selectivity.

Anisotropy↗
PubMed2002

Synthesis, crystal structure, and H/D exchange of the inside protonated form of the cage imine 4,8,12-triaza-1-azoniatricyclo[6.6.3.2(4,12)]nonadec-1(15)-ene. A model for proton transfer through an aliphatic membrane.

The reaction of the inside protonated form of the tricyclic amine 1,4,8,12-tetraazatricyclo[6.6.3.2(4,12)]nonadecane (1) with iron(III) affords the inside monoprotonated form of the corresponding imine 4,8,12-triaza-1-azoniatricyclo[6.6.3.2(4,12)]nonadec-1(15)-ene (2), which was isolated as the tetrabromozincate salt (2a) in a yield of 78%. The crystal structure of 2a has been solved by X-ray diffraction at T = 120 K. In the imine cation the acidic hydrogen atom and the lone pairs of the nitrogen atoms are oriented toward the inside of the cavity. The acidic hydrogen atom is bound to a nitrogen atom belonging to the triazacyclononane entity. The imine double bond is situated between the N-atom of the triazacyclononane entity and the C-atom belonging to one of the three trimethylene bridges. The imine 2 is stable in acidic solution and the inside coordinated proton is very robust in acidic solution. In basic solution the imine reacts fast to give a quantitative formation of the inside protonated form of the hemiaminal 1,4,8,12-tetraazatricyclo[6.6.3.2(4,12)]nonadecan-5-ol (3). The equilibrium constant K(im) = [3][H(+)]/[2] was determined at three different temperatures from potentiometric measurements, which gave K(im) = 1.57(1) x 10(-5) M at 25 degrees C, Delta S degrees = -83(1) J mol(-1) K(-)(1),and Delta H degrees = 2.6(3) kJ mol(-1) at I = 1.0 M (NaCl). The inside coordinated proton in 3 is labile in basic solution and the rate for NH/ND exchange was determined by (1)H NMR at three different temperatures. The reaction followed the expression k(obs) = k(ex)[OD(-)] with k(ex) = 0.0978(30) dm(3) mol(-1) s(-1) at 25 degrees C, Delta S(++) = 87(4) J mol(-1) K(-1), and Delta H(++) = 104.9(11) kJ mol(-1) at I = 1.0 M (NaCl). The exchange rate is more than 5 x 10(6) times faster than that of the parent saturated cage 1. This extreme enhancement of reactivity is explained by an intramolecular proton transfer reaction mediated by hydroxy and oxy groups flipping in and out of the cavity, which mechanistically has resemblance to the transport of ions in a biological system.

Journal Article↗
PubMed1996

Formation of two double-strand breaks in the same DNA molecule by a single high-energy photon or ionizing particle.

I calculate the probability that a single high-energy ionizing particle or photon makes two widely spaced double-strand breaks in the same DNA molecule. Deletions (or inversions) between two breaks formed by the same incident particle are linear in radiation dose and occur even at extremely low dose-rates; deletions between breaks induced by separate particles are quadratic in dose and are much fewer at very low dose-rate. The calculations show that for a few grays of sparsely ionizing radiations such as fast electrons, X-rays of gamma-rays, the formation of two double-strand breaks in a DNA molecule 1 megabase in size should be nearly entirely quadratic in dose. For heavily ionizing particles such as alpha particles from radon products, the linear and quadratic terms are comparable in size. These conclusions are robust and insensitive to details of the calculations. The results are essentially the same for DNA in a random coil configuration and for DNA uniformly and randomly distributed within a sphere.

Chromosome Inversion↗
PubMed2005

DNA damage produced by 125I-triplex-forming oligonucleotides as a measure of their successful delivery into cell nuclei.

Decay of an Auger-electron-emitting radioisotope can knock out a targeted gene by producing DNA strand breaks within its sequence. For delivery of Auger emitters to genomic targets we used triplex-forming oligonucleotides (TFOs) that bind specifically to their target sequences by forming hydrogen bonds within the major groove of the target duplex. We named this approach antigene radiotherapy. In our previous studies, we demonstrated that (125)I-labeled TFOs targeted against the human MDR1 gene produced sequence-specific double strand breaks (DSBs) within this gene in live cultured cells. We also found that conjugation of TFO with nuclear localization signal peptide significantly increased the efficiency of targeting. To screen the wide variety of possible TFO modifications a sensitive and robust assay of DNA damage produced by such (125)I-TFOs would be highly desirable. Recently we showed a direct correspondence between the number of decays of (125)I incorporated into DNA as (125)I-UdR and the number of histone gamma-H2AX foci per cell revealed by staining with gamma-H2AX antibodies. The technique is 100-fold more sensitive than other DSB-detection methods, thus it is possible to detect as few as an average of 0.5 DSBs per cell in a population of cultured cells. Here we applied this method to evaluate the intracellular DNA damage produced by two (125)I-TFOs, the first targeted to the single-copy HPRT gene ((125)I-TFO-HPRT) and second to a multicopy repeated sequence (GA)(n) that occurs almost 7000 times in the human genome ((125)I-TFO-GA). DNA damage produced by (125)I-TFO was assessed by staining the cells with gamma-H2AX antibody followed by either direct counting gamma-H2AX foci or by measuring the gamma-H2AX signal using flow cytometry. Both methods produced quantitatively close results; (125)I-TFO-GA with multiple nuclear targets produced on average 1.93 times more gamma-H2AX foci per cell and generated 1.96 times increase in gamma-H2AX antibody staining signal than (125)I-TFO-HPRT with a single target. The gamma-H2AX-based assay requires considerably less time and effort than the direct measurement of DSB by Southern hybridization applied previously. Therefore, we believe that gamma-H2AX-based measurement of DNA damage could be useful for evaluation and cellular DNA accessibility by (125)I-labeled DNA targeting agents.

Base Sequence↗
PubMed2005

Robust determination of optical path difference: fringe tracking at the infrared optical telescope array interferometer.

We describe the fringe-packet tracking system used to equalize the optical path lengths at the Infrared Optical Telescope Array interferometer. The measurement of closure phases requires obtaining fringes on three baselines simultaneously. This is accomplished by use of an algorithm based on double Fourier interferometry for obtaining the wavelength-dependent phase of the fringes and a group-delay tracking algorithm for determining the position of the fringe packet. A comparison of data acquired with and without the fringe-packet tracker shows a factor of approximately 3 reduction of the error in the closure-phase measurement. The fringe-packet tracker has been able so far to track fringes with signal-to-noise ratios as low as 1.8 for stars as faint as mH = 7.0.

Journal Article↗
PubMed2001

Acute dietary tryptophan depletion impairs maintenance of "affective set" and delayed visual recognition in healthy volunteers.

RATIONALE: Altered serotonergic transmission in affective disorders and Alzheimer's disease has prompted research aimed at defining the precise cognitive effects of depleting central serotonin in humans, using acute dietary tryptophan depletion. OBJECTIVE: We examined the effects of tryptophan depletion on mood and cognition in healthy volunteers. Cognitive tests of memory and attentional processing were employed to test hypotheses of central 5-hydroxytryptamine (5-HT) function related to cortical processing. METHODS: A double-blind, parallel design, placebo control study was employed with 15 subjects in each group. Mood rating scales were performed at the start and 5 h after ingestion of the drink. Cognitive tests were also performed at 5 h, after completion of the subjective rating scales. RESULTS: A robust reduction in total tryptophan was achieved in the test group. Subjects receiving the placebo drink showed the expected effect of shift on the affective shifting task, that is, more errors in the more difficult shift versus the non-shift condition. The tryptophan-depleted group made a similar number of errors in the shift trials but failed to reduce the number of errors in the non-shift trials. The tryptophan-depleted group showed a significant impairment on the delayed pattern recognition task. No significant effects on the subjective mood measures were found. CONCLUSIONS: Tryptophan depletion abolished the normal tendency to improve error scores on non-shift trials in response to affective cues on a go/no-go task. We suggest that this inability to "maintain set" in the non-shift condition may be due to a disruption of semantic retrieval processes concerned with affect. The novel finding of impairment on a delayed visual pattern recognition task confirms and extends previous studies where selective effects on memory and learning have been found following acute tryptophan depletion.

Adult↗