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PubMed2006

Perceptual learning in speech: stability over time.

Perceptual representations of phonemes are flexible and adapt rapidly to accommodate idiosyncratic articulation in the speech of a particular talker. This letter addresses whether such adjustments remain stable over time and under exposure to other talkers. During exposure to a story, listeners learned to interpret an ambiguous sound as [f] or [s]. Perceptual adjustments measured after 12 h were as robust as those measured immediately after learning. Equivalent effects were found when listeners heard speech from other talkers in the 12 h interval, and when they had the opportunity to consolidate learning during sleep.

Attention↗
PubMed2006

Stages of abstraction and exemplar memorization in pigeon category learning.

It has been proposed that human category learning consists of an early abstraction-based stage followed by a later exemplar-memorization stage. To investigate whether similar processing stages extend to category learning in a nonverbal species, we applied a prototype-exception paradigm to investigating pigeon category learning. Five birds and 8 humans learned six-dimensional perceptual categories constructed to include prototypes, typical items, and exceptions. We evaluated the birds' and humans' categorization strategies at different points during learning. Early on in both species, prototype performance improved rapidly as exception performance remained below chance, indicating an initial mastery of the categories' general structure. Later on, exception performance improved selectively and dramatically, indicating exception-item resolution and exemplar memorization. Abstraction- and exemplar-based formal models reinforced these interpretations. The results suggest a psychological transition in pigeon category learning from abstraction- to exemplar-based processing similar to that found in humans.

Animals↗
PubMed2002

Novel object presentation affects sleep-wake behavior in rats.

Sleep is suggested to be crucial for the processing and storage of new information. Several learning tasks have been shown to increase the amount of rapid eye movement sleep (REMS) with its typical theta activity (6-8 Hz) relative to total sleep time. Vice versa, REMS deprivation is able to affect memory consolidation following some, but not all learning tasks. Furthermore, recent studies have shown an increase of spindle activity (12-15 Hz) within the electroencephalogram (EEG) of nonREMS as well. The enhancement of both spindle and theta activity is suggested to serve as background activity for the synchronization of those neuronal pathways that were involved in the registration and, later on, participate in the long-term storage of new information in defined brain regions. In the present study, the presentation of a novel object to rats enhanced the amount of preREMS, an intermediate sleep stage with high spindle activity, within the first 2 h of the subsequent sleeping phase. Four hours later, the amount of REMS was increased as well. However, there were no changes in the EEG power spectra of nonREMS, preREMS and REMS. We therefore hypothesize that the increase of preREMS and REMS amounts and the related spindle and theta activity stand for the processing and storage of new information about the presented novel objects.

Action Potentials↗
PubMed1999

Speech-sound discrimination in school-age children: psychophysical and neurophysiologic measures.

This study measured behavioral speech-sound discrimination and a neurophysiologic correlate of discrimination in normal school-age children (ages 6 to 15) to determine if developmental effects exist. Just noticeable differences (JNDs) and mismatch responses (MMNs) were assessed for synthetic syllables that differed in third-formant onset frequency (/da-ga/) and formant transition duration (/ba-wa/). These stimuli were selected because children with learning problems often find it difficult to discriminate rapid spectrotemporal changes like /da-ga/, whereas the ability to distinguish /ba-wa/ is relatively unimpaired. Results indicate that JNDs for /da-ga/ show no developmental effects and that JNDs for /ba-wa/ decrease slightly with age (although likely for task-related reasons). MMNs elicited by two /da-ga/ stimulus pairs (onset frequency differences = 20 Hz, 280 Hz) and three /ba-wa/ stimulus pairs (transition duration differences = 3, 5, 15 ms) showed no systematic or significant differences for onset latency, duration, or area as a function of age. Normative JND and MMN data are provided. These norms provide a metric against which children with suspected central auditory processing difficulties or auditory-based language disorders can be compared.

Adolescent↗
PubMed2005

Apheresis for MPO-ANCA-associated RPGN-indications and efficacy: lessons learned from Japan nationwide survey of RPGN.

A national survey concerning rapidly progressive glomerulonephritis (RPGN) was conducted in Japan between 1989 and 2000 and resulted in the registration of 715 patients with RPGN. Among the documented patients, the most frequent primary disease was primary pauci-immune crescentic glomerulonephritis (n = 283), and the second most frequent was microscopic polyangitis (n = 127). Overall, 370 patients had MPO-ANCA, and 23 patients had PR3-ANCA. We found that both renal and patient survivals were significantly worse in patients with MPO-ANCA-associated RPGN than patients with PR3-ANCA. Fifty-three patients received apheresis therapy with various combinations of immunosuppressive regimens. They had higher serum creatinine, higher CRP, and a higher frequency of complicated pulmonary involvements as compared to the controls without apheresis therapy. In dialysis-dependent patients, no additional benefit from apheresis therapy was observed. Only pulmonary renal syndrome patients with CRP > 6 mg/dl at presentation showed a slightly better prognosis (patient survival with apheresis; 66.7%, without apheresis; 56.7%). Furthermore, a rapid MPO-ANCA titer reduction was observed in patients treated with apheresis. Patients with MPO-ANCA-associated RPGN were older, and had more chronic and sclerotic lesions than patients with PR3-ANCA-associated RPGN. Based on these findings, we suggest that a lower dose of immunosuppressant should be considered in order to avoid opportunistic infection. In this situation, cytapheresis is the treatment of choice. Nevertheless, in patients with an aggressive form of RPGN with rapid deterioration of renal function like the PR3-ANCA-associated RPGN, or pulmonary renal syndrome complicated severe inflammation, or relapses with high MPO-ANCA titer, we conclude that apheresis therapy should be considered.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2006

Protein therapeutics--lessons learned and a view of the future.

Protein therapeutics represent a rapidly growing proportion of marketed drugs and have an undisputed place alongside chemistry-based oral therapies; indeed, for certain indications they are the only effective therapy. Therapeutic proteins can be mined from diverse sources to target interactions that are not accessible to small molecules, and can be engineered to have optimal pharmacological properties. Nevertheless, the development of such therapeutics is hampered by several issues, such as cost of production, patient compliance, immunogenicity and reticence of reimbursement agencies to pay for their use in chronic treatment. Herein we review some of these issues in detail. The application of technological advancements will address some of these issues and enable the development of a growing number of biological therapies that will continue to improve patient quality of life for decades to come.

Animals↗
PubMed1997

On-site, rapid HIV testing with same-day results and counseling.

BACKGROUND: New rapid HIV antibody tests have allowed provision of results and result-specific counseling on the day on initial visit, and have the potential to increase the efficiency of HIV counseling and testing. METHODS: To evaluate the use of rapid testing with same-day results in public clinics, the Single Use Diagnostic System HIV-1 rapid assay was used for a 3-month period at an anonymous testing clinic and a sexually transmitted disease (STD) clinic in Dallas, Texas. Non-reactive rapid test results were reported as HIV-negative. Reactive results were reported as 'preliminary positive'. These procedures were compared with standard testing during a baseline period, with respect to number of clients receiving results and post-test counseling, client satisfaction, counselor acceptance, cost and effectiveness at reducing HIV risk. RESULTS: Rapid testing resulted in an increase in the number of persons learning their serostatus: a 4% increase for uninfected and a 16% increase for infected clients at the Anonymous Testing Clinic; a 210% increase for uninfected patients and a 23% increase for infected patients at the STD clinic. Rapid testing resulted in a cost saving of US$ 11 per test in both the anonymous and STD clinics. Of those previously tested, 88% responded that they preferred the rapid test. In the year following initial HIV test, clients tested with rapid and standard procedures were equally likely to return to the clinic with a new STD (odds ratio, 0.97; 95% confidence interval, 0.7-1.4). CONCLUSIONS: Rapid, on-site HIV testing was feasible, preferred by clients, and, resulted in significant improvement in the number of persons learning their serostatus, without increasing the costs or decreasing the effectiveness of counseling and testing.

Counseling↗
PubMed2006

One-trial associative odor learning in neonatal mice.

Behavior genetics studies in mice demand efficient training protocols for rapid phenotypic screening. However, the capacity of neonatal mice to form and retain associative memories has been difficult to study due to their limited sensorimotor capacities. The present study describes a method for robust, naturalistic associative learning in neonatal mice as young as 3 days old. After removal of the dam from the home cage for 2 h, preweanling CD-1 mice of ages 3, 5, and 10 days postnatal were conditioned to associate an arbitrary odorant with the suckling and milk delivery that ensued upon her return to the home cage. After a second maternal deprivation, neonates were tested on their acquired preference for that odorant. Neonates exhibited a learned preference for the conditioned odorant over a novel control odorant. No learning was observed without deprivation, that is, when the dam was removed only briefly for scenting. One-trial learning sufficed to show clear preferences for the conditioned odorant, although repeated training (three sessions over 8 days) significantly increased the expression of preference. The development of neonatal associative learning protocols requiring minimal human intervention is important for the behavioral phenotyping of mutant and transgenic strains, particularly those modeling developmental disorders.

Animals↗
PubMed2006

The primate amygdala represents the positive and negative value of visual stimuli during learning.

Visual stimuli can acquire positive or negative value through their association with rewards and punishments, a process called reinforcement learning. Although we now know a great deal about how the brain analyses visual information, we know little about how visual representations become linked with values. To study this process, we turned to the amygdala, a brain structure implicated in reinforcement learning. We recorded the activity of individual amygdala neurons in monkeys while abstract images acquired either positive or negative value through conditioning. After monkeys had learned the initial associations, we reversed image value assignments. We examined neural responses in relation to these reversals in order to estimate the relative contribution to neural activity of the sensory properties of images and their conditioned values. Here we show that changes in the values of images modulate neural activity, and that this modulation occurs rapidly enough to account for, and correlates with, monkeys' learning. Furthermore, distinct populations of neurons encode the positive and negative values of visual stimuli. Behavioural and physiological responses to visual stimuli may therefore be based in part on the plastic representation of value provided by the amygdala.

Amygdala↗
PubMed1988

Differential forgetting in patients with temporal lobe dysfunction.

Delayed recall performance was investigated in 13 patients with temporal lobe epilepsy (TLE) and 13 healthy age-matched controls who were matched on a pairwise basis for initial learning on the Selective Reminding test. TLE patients performed significantly worse on the 30-minute delayed recall condition despite equivalent initial continuous long-term retrieval scores. These data suggest that TLE patients forget at disproportionately rapid rates as compared to healthy controls despite equivalent initial learning. Consequently, delayed recall may increase group discrimination when initial learning levels are similar.

Journal Article↗
PubMed1978

Changes in pattern discrimination learning induced by visual deprivation in normal and commissurotomized pigeons.

The effect of monocular (MD), binocular (BD) and alternating monocular (AMD) deprivation on monocular pattern discrimination learning and interocular transfer was investigated in pigeons reared with intact and sectioned supraoptic decussation (DSO). In BD and AMD animals acquisition and interocular transfer of two different pattern discrimination problems remained as good as in the control animals (CO). Monocularly deprived animals (MDE) required significantly more trials to learn the discriminations through the deprived eye, when it was trained first, and interocular transfer from the deprived to the experienced eye was absent. However, if the experienced eye was trained first (MED), learning with the deprived eye was at least as rapid as with the experienced eye. This indicates positive interocular transfer from the experienced to the deprived eye. Interocular transfer of pattern discriminations was completely blocked by section of the DSO in both adults (DSOad) and newly hatched animals (DSOjuv). The elimination of binocular interaction by commissurotomy from the beginning of the postnatal life failed to produce an impaired pattern discrimination learning in monocularly deprived animals.(MD+DSO). The results are discussed in terms of competition between the projections from both eyes in the visual Wulst.

Animals↗
PubMed2000

Reference memory, anxiety and estrous cyclicity in C57BL/6NIA mice are affected by age and sex.

Age-related changes in learning and memory are common in rodents. However, direct comparisons of the effects of aging on learning and memory in both males and females are lacking. The present study examined whether memory deteriorates with increasing age in C57BL/6NIA mice, and whether age-related changes in learning and memory are similar in both sexes. Male and female mice (five, 17 and 25 months of age) were tested in a battery of behavioral tasks including the Morris water maze (spatial and non-spatial reference memory), simple odor discrimination (olfactory reference memory), plus maze (anxiety/exploration), locomotor activity, and basic reflexes. Five-month-old mice learned the water maze and odor discrimination tasks rapidly. Relative to five-month-old mice, 25-month-old mice exhibited impaired spatial and olfactory reference memory, but intact non-spatial reference memory. The spatial reference memory of 17-month-old mice was also impaired, but less so than 25-month mice. Seventeen-month-old mice exhibited intact non-spatial (visual and olfactory) reference memory. Five and 25-month-old mice had similar levels of plus maze exploration and locomotor activity, whereas 17-month-old mice were more active than both groups and were slightly less exploratory than five-month-old mice. Although sex differences were not observed in the five- and 25-month groups, 17-month-old females exhibited more impaired spatial reference memory and increased anxiety relative to 17-month-old males. Estrous cycling in females deteriorated significantly with increased age; all 25-month-old females had ceased cycling and 80% of 17-month-old females displayed either irregular or absent estrous cycling. This study is the first to directly compare age-related mnemonic decline in male and female mice. The results suggest that: (i) aged mice exhibit significant deficits in spatial and olfactory reference memory relative to young mice, whereas middle-aged mice exhibit only a moderate spatial memory deficit and; (ii) spatial reference memory decline begins at an earlier age in females than in males, a finding that may be related to the cessation of estrous cycling.

Aging↗
PubMed1984

Preserved learning in monkeys with medial temporal lesions: sparing of motor and cognitive skills.

In an effort to bring into correspondence the findings from human amnesic patients and the findings from monkeys with surgical lesions of those brain regions thought to be affected in the human cases, we have addressed in three experiments the implication of findings that human amnesia spares motor and cognitive skills. In the first experiment, monkeys with conjoint lesions of hippocampus and amygdala (H-A), which reproduced the surgical removal sustained by the noted amnesic case H.M., were only mildly impaired in learning relatively difficult pattern discrimination tasks. Monkeys with lesions of temporal stem matter (TS) were severely impaired on the same tasks, due to an apparent deficiency in visual information processing. In the second experiment, monkeys with H-A lesions were severely impaired at learning relatively easy discrimination tasks that could be acquired rapidly by normal monkeys. Monkeys with TS lesions were not impaired. In the third experiment, monkeys with H-A lesions exhibited normal acquisition of two motor skill tasks. These data can be understood in the light of a distinction between kinds of memory, founded in recent studies of the neuropsychology of human amnesia. These studies have led to a distinction between the learning of skills or procedures, which is spared in human amnesia, and the learning of facts and episodes, which is impaired. Monkeys with H-A lesions are normal at skill learning like human amnesic patients with similar lesions. This conclusion depends in part on the argument developed here that pattern discrimination learning, as accomplished by monkeys, has a large skill-like component. These results bring into correspondence the behavioral data from human amnesic patients and operated monkeys and set the stage for identifying precisely what brain structures must be damaged to produce amnesia.

Amnesia↗
PubMed1988

Starch-based conditioned flavor preferences in rats: influence of taste, calories and CS-US delay.

Six experiments examined the rat's preference for flavors associated with hydrolysed starch (Polycose) solutions. Hungry rats developed a preference for a flavor (CS+) mixed into a saccharin-sweetened 16% Polycose solution over a flavor (CS-) mixed in saccharin-water. The addition of acarbose, a drug which inhibits starch digestion, to the Polycose solution blocked the flavor preference. This finding indicates that it is the postingestive rather than the taste properties of Polycose that condition flavor preferences. Rats also developed a preference for a CS+ flavor that preceded the ingestion of a Polycose solution by 10 min. This flavor conditioning, however, was not obtained in all experiments. Some CS flavors may be more effective than others in producing conditioned flavor preferences over a delay. Preference conditioning over a delay was facilitated when the rats had previously learned that the taste of the US (Polycose) was not associated with rapid caloric repletion; this was accomplished by giving the rats prior exposure to a Polycose + acarbose solution. Rats with such pre-exposure learned to prefer a CS + flavor that preceded by 10 to 60 min the consumption of a Polycose solution (without acarbose). The results demonstrate that calorie-based flavor preferences can be conditioned over a delay, but conditioning is influenced by the nature of the CS and US stimuli used.

Acarbose↗
PubMed1999

Behavioral development and olfactory learning in the honeybee (Apis mellifera).

Honeybees (Apis mellifera) can be readily conditioned in the laboratory to specific odors paired with a subsequent sucrose reward. A series of experiments are reported which demonstrate that the ability of bees to acquire and retain this learning is affected by the stage of behavioral development (caste). Results show rapid acquisition of the proboscis extension reflex (PER) conditioning in adult forager bees, however much slower acquisition and poorer retention of the same learning paradigm in younger adults, i.e., nurse bees and guard bees. Further, if nurse bees are made to forage precocially by manipulation of the hive population, these bees show excellent acquisition and retention of PER conditioning comparable to normal adult forager bees. Results are discussed in terms of olfactory learning requirements of bees performing caste-specific behaviors and the maturation of the bee nervous system.

Age Factors↗
PubMed2003

Paralinguistic correlates of conceptual structure.

How is conceptual knowledge transmitted during conversation? When a speaker refers to an object, the name that the speaker chooses conveys information about category identity. In addition, I propose that a speaker's confidence in a classification can convey information about category structure. Because atypical instances of a category are more difficult to classify than typical instances, when speakers refer to these instances their lack of confidence will manifest itself "paralinguistically"--that is, in the form of hesitations, filled pauses, or rising prosody. These features can help listeners learn by enabling them to differentiate good from bad examples of a category. So that this hypothesis could be evaluated, in a category learning experiment participants learned a set of novel colors from a speaker. When the speaker's paralinguistically expressed confidence was consistent with the underlying category structure, learners acquired the categories more rapidly and showed better category differentiation from the earliest moments of learning. These findings have important implications for theories of conversational coordination and language learning.

Cognition↗
PubMed2000

Two intertidal fish species use visual association learning to track the status of food patches in a radial maze.

We tested fifteen-spined sticklebacks, Spinachia spinachia, and corkwing wrasse, Crenilabrus melops, for their ability to associate visual spatial cues with food sources in a radial maze and so to track renewal frequencies and productivity. When all locations contained food or were empty, subjects displayed win-shift or lose-shift behaviour by avoiding recently visited locations; this behaviour therefore appeared to be a basic trait. Both species readily learned food-cue associations, although with less efficiency as the diversity of cues increased. They used this information to distinguish food sources renewed within and between daily foraging bouts from those that remained empty. Moreover, both species distinguished between renewable food sources differing in productivity, preferentially visiting those containing more food. Reversal of cue roles caused an immediate decline in foraging efficiency, followed by rapid recovery as new food-cue associations were learned. Evidently, therefore, subjects tracked the status of potential food sources by continued sampling and could switch from win-shift to win-stay behaviour, when preferred locations were persistently revisited, as appropriate. The formation of food-cue associations, together with sampling and flexible use of win-shift and win-stay behaviour, would enable these rocky intertidal fish species to exploit patchily distributed food sources whose status changes during the tidal cycle. Copyright 2000 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1989

Appetitive learning in snails shows characteristics of conditioning in vertebrates.

The snail Lymnaea stagnalis can be rapidly conditioned to produce feeding response to a previously neutral tactile stimulus, repeatedly and specifically paired with positive reinforcement (food). The conditioned response has many of the same characteristics seen in appetitive learning in vertebrates. The relative simplicity of the molluscan CNS and the detailed knowledge of the neural circuitry underlying feeding in Lymnaea will facilitate the neurophysiological analysis of appetitive learning as well as stimulus generalization, discriminative learning and generalization of extinction all described in the present paper.

Animals↗