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PubMed2004

Prefrontal-hippocampal dynamics involved in learning regularities across episodes.

Using functional magnetic resonance imaging, the neural correlates of context-specific memories and invariant memories about regularities across episodes were investigated. Volunteers had to learn conjunctions between objects and positions. In an invariant learning condition, positions were held constant, enabling subjects to learn regularities across trials. By contrast, in a context-specific condition object-position conjunctions were trial unique. Performance increase in the invariant learning condition was paralleled by a learning-related increase of inferior frontal gyrus activation and ventral striatal activation and a decrease of hippocampus activation. Conversely, in the context-specific condition hippocampal activation was constant across trials. We argue that the learning-related hippocampal activation pattern might be due to reduced relational binding requirements once regularities are extracted. Furthermore, we propose that the learning-related prefrontal modulation reflects the requirement to extract and maintain regularities across trials and the adjustment of object-position conjunctions on the basis of the extracted knowledge. Finally, our data suggest that the ventral striatum encodes the increased predictability of spatial features as a function of learning. Taken together, these results indicate a transition of the relative roles of distinct brain regions during learning regularities across multiple episodes: regularity learning is characterized by a shift from a hippocampal to a prefrontal-striatal brain system.

Adult↗
PubMed2005

Language-experience facilitates discrimination of /d-th/ in monolingual and bilingual acquisition of English.

To trace how age and language experience shape the discrimination of native and non-native phonetic contrasts, we compared 4-year-olds learning either English or French or both and simultaneous bilingual adults on their ability to discriminate the English /d-th/ contrast. Findings show that the ability to discriminate the native English contrast improved with age. However, in the absence of experience with this contrast, discrimination of French children and adults remained unchanged during development. Furthermore, although simultaneous bilingual and monolingual English adults were comparable, children exposed to both English and French were poorer at discriminating this contrast when compared to monolingual English-learning 4-year-olds. Thus, language experience facilitates perception of the English /d-th/ contrast and this facilitation occurs later in development when English and French are acquired simultaneously. The difference between bilingual and monolingual acquisition has implications for language organization in children with simultaneous exposure.

Canada↗
PubMed2005

Chemistry of the mind: neurochemical modulation of prefrontal cortical function.

The neurochemical modulation of prefrontal cortical function is reviewed with special reference to the ascending dopaminergic and serotoninergic projections. Evidence is surveyed from studies of rats, nonhuman primates, and humans to suggest that prefrontal dopamine has specific functions in attentional control and working memory, mediated mainly through the D1 receptor, whereas manipulations of serotonin are shown by contrast to affect reversal learning in monkeys and human volunteers and measures of impulsivity in rats. These findings are discussed in the context of these as well as other neurotransmitter systems (including noradrenaline and acetylcholine) having distinct roles in the neuromodulation of prefrontal cortical function. The capacity of the prefrontal cortex itself to exert top-down regulation of these ascending neurochemical systems is also discussed.

Animals↗
PubMed1993

The ESEM used to image crystalline structures of polymers and to image ink on paper.

This article describes two cases in which the advantages of the ESEM have been exploited in unanticipated ways. First, we have found that etching occurs as the electron beam scans the surface of uncoated polymers in the ESEM. The surface topography caused by this etching, as seen in ESEM images, reflects the morphology of crystalline structures in the polymers. This technique has been valuable in the study of such textures in polymers. The second application is related to our use of the ESEM in support of research on the deinking of paper. In this effort we have learned that an unconventional contrast mechanism can be used during ESEM imaging to distinguish between inked and non-inked areas of newsprint. Under usual operating conditions, ESEM imaging does not distinguish between inked and non-inked areas. However, at relatively low sample chamber pressures the non-inked areas appear brighter than inked areas in ESEM images.

Crystallization↗
PubMed2005

Medium-term effects of chemotherapy in older cancer patients.

PURPOSE: To address the lack of research in older cancer patients, the present study prospectively evaluated their cognitive functions across the first six months following diagnosis and chemotherapy. PATIENTS AND METHODS: A total of 77 younger (n=43, age < 60) and older (n=34, age > or = 60) cancer patients with hematological disease or cancer of the intestinal tract took part in the study. Medium-term effects of chemotherapy were examined in these cancer patients by means of a battery of cognitive tests during baseline and six months after start of treatment. RESULTS: In contrast to baseline verbal learning, word fluency and memory capacity improved in all patients six months after start of treatment. A negative effect of age on cognitive functions could not be demonstrated. Additionally, depression was neither associated with medium-term effects of chemotherapy nor was it related to age. CONCLUSION: The results suggest that chemotherapy has no negative effects on cognitive functions after the first six months following the onset of treatment. It was demonstrated that complete recovery of cognitive functions is independent of the patient's age.

Adult↗
PubMed1984

Patterns of confidence loss in the cued recall of normal people with attenuated recognition memory: their relevance to a similar amnesic phenomenon.

Amnesics show relatively good cued recall (but very poor recognition memory) yet display little confidence in the accuracy of their cued recall responses. In the two studies reported here a similar pattern of results was found in normal subjects who were either tested after a long retention interval or after being given inadequate time to learn target words, i.e. cued recall was relatively unaffected whereas both yes/no recognition of words and confidence in cued recall were much impaired. The finding of equivalent impairment in recognition and confidence in cued recall suggests that these forms of memory are mediated by common memory mechanisms. These mechanisms must be impaired in amnesics and, in normal subjects, are very sensitive to delay and learning exposure manipulations. In contrast, cued recall depends largely on a different form of memory spared in amnesics, and which in normal subjects is less susceptible than recognition memory to delay and brief exposure manipulations.

Adolescent↗
PubMed2006

Warming up improves speech production in patients with adult onset myotonic dystrophy.

UNLABELLED: This investigation was conducted to study whether warming up decreases myotonia (muscle stiffness) during speech production or causes adverse effects due to fatigue or exhaustion caused by intensive speech activity in patients with adult onset myotonic dystrophy. Thirty patients with adult onset myotonic dystrophy (MD) and ten healthy controls were examined, using a protocol that requires subjects, to speak continuously for at least 10 min. In MD patients, warming up led to an increase in speech rate and a decrease in speech variability without causing signs of fatigue or exhaustion as a result of prolonged and intensive use of the speech musculature. No significant changes were found in the controls. After warming up, MD patients achieved a habitual speech rate in reading and reciting similar to that of healthy controls. LEARNING OUTCOMES: As a result of this activity the reader will learn that 1. In contrast to most neuromuscular disorders, speech production in patients with adult onset myotonic dystrophy improves by activity. 2. Myotonia in speech musculature in patients with adult onset myotonic dystrophy can be reduced by instructing them to warm up their muscles by repetitive movements. 3. Warming up is a valuable intervention because it improves the velocity and fluency of speech production without aggravating the signs of flaccid dysarthria.

Adolescent↗
PubMed2006

Multiple effects of pentyl-4-yn-VPA enantiomers: from toxicity to short-term memory enhancement.

2-n-Pentyl-4-pentynoic acid (PE-4-yn-VPA) is a derivative of the antiepileptic and mood-stabilizing drug valproic acid (VPA). PE-4-yn-VPA exists as R- and S-enantiomers, the latter being more teratogenic. PE-4-yn-VPA also possesses antiepileptic, antiproliferative, and cell-differentiating properties. Moreover, the less teratogenic enantiomer, R-PE-4-yn-VPA, was recently shown to improve learning and memory. We here present a detailed investigation of the enantioselective properties of PE-4-yn-VPA using a range of in vitro and in vivo assays including measurements of cellular growth and migration, neuronal differentiation and survival, intracellular signal transduction, synaptic plasticity and maturation, and short-term memory as determined by the social recognition test. The results show that the enantiomers of PE-4-yn-VPA largely had similar effects in vitro. However, in all in vitro experiments the more teratogenic enantiomer, S-PE-4-yn-VPA, exhibited a stronger potency than R-PE-4-yn-VPA, and only S-PE-4-yn-VPA had a detrimental effect on cell survival. Interestingly, both the R- and S-enantiomer improved learning and memory. In contrast, the beneficial effect of S-PE-4-yn-VPA on memory was lost by time, whereas the effect of R-PE-4-yn-VPA administration was longer lasting, suggesting that the beneficial effect of the S-enantiomer on memory formation may be counteracted by its detrimental effect on neuronal cell survival.

Analysis of Variance↗
PubMed2004

Can infants' object concepts be trained?

Decades of research and debate on the origins of object permanence in infancy have contrasted various types of learning with possible innate contributions. A recent paper by Johnson et al. adds a new perspective to this debate by reporting that even very brief training periods can dramatically influence infants' persisting object representations. Such training studies have the potential to constrain 'nature versus nurture' debates in novel ways, although important challenges remain.

Age Factors↗
PubMed2002

Neuropsychological performance in schizotypal personality disorder: evidence regarding diagnostic specificity.

BACKGROUND: Individuals with schizotypal personality disorder (SPD) share cognitive deficits with schizophrenic patients, suggesting that these deficits represent a core feature of the schizophrenia spectrum. We investigated the neuropsychological profile in SPD patients compared with two comparison groups: healthy volunteers (HV) and patients who met criteria for another non-schizophrenia spectrum personality disorder (NSS). METHODS: We tested 48 DSM-III-R SPD patients, 22 NSS and 32 HV on a neuropsychologic battery that included the California Verbal Learning Test (CVLT), Trail Making A and B, the DOT test of working memory, the Stroop Color-Word Interference, the Paced Auditory Serial Addition Test (PASAT), the Wechsler Memory Scale Visual Reproduction Test (WMSV-R), and the Wechsler Adult Intelligence Scale vocabulary and block design. RESULTS: Normative standards for performance were created using the HV group. SPD patients performed significantly worse compared with HVs; specifically, SPD patients demonstrated impaired performance on the PASAT and the WMSV-R immediate and delayed recall compared to HV. Moreover, SPD patients were impaired in the PASAT and the WMSV-R immediate condition compared with the NSS group. The NSS patients did not differ from HV on any of the cognitive tasks. The interpersonal factor of the schizotypal symptoms inversely correlated with the PASAT score (r = -.32, p <.006). CONCLUSIONS: Compared with HVs, SPD patients demonstrate modest cognitive impairment. These differences reached statistical significance for the PASAT (an auditory working memory task), and the WMSV-R immediate and delayed recall (a learning-recall test). In contrast, performance of NSS patients did not differ from that of HVs. The types of deficits observed in SPD patients are qualitatively similar to but milder than those seen in patients with schizophrenia.

Adult↗
PubMed2001

Development of syllable structure in English-speaking children with particular reference to rhymes.

This study investigates acquisition of the rhyme using cross-sectional and longitudinal data from 14 English-speaking children (aged 1;3-2;0). It focuses on 4 questions pertaining to rhyme development, which are motivated from current theories of prosodic acquisition: 1. Do children make vowel length errors in early acquisition?; 2. Do children acquire coda consonants before they learn the vowel length contrast?; 3. What consonants are first acquired as codas?; and 4. Is there a size constraint such that children's productions are minimally and maximally bimoraic? The results indicate that the percentage of vowel length errors across all children was low irrespective of the percentage of codas produced. In particular, two children produced very few coda consonants and made few vowel length errors, suggesting that mastery of vowel length was not secondary to coda acquisition. With respect to coda segments, children produced voiceless obstruents as codas before sonorants supporting generally the claim that obstruents emerge before sonorants in coda position. Children produced coda consonants more frequently after short than long vowels consistent with a bimoraic size constraint in syllable development. The paper concludes by comparing the English findings with cross-linguistic work on vowel length acquisition.

Child Language↗
PubMed1983

Vagotomy produces learned food aversions in the rat.

Subdiaphragmatic vagotomy produces hypophagia and weight loss in normal rats and can reverse the hyperphagia and obesity of rats with ventromedial hypothalamic lesions. Vagotomy surgery can also produce symptoms of nausea and discomfort. Since such symptoms are highly effective as unconditioned stimuli in food aversion conditioning, the present studies examined whether some of the depression in food intake observed in rats with vagotomy could be due to the development of aversions to the foods eaten after their surgery. In the first study, significant aversions developed to the specific novel diet consumed after vagotomy, results indicating that the symptoms associated with vagotomy can serve as effective unconditioned stimuli in the acquisition of learned food aversions. The second study compared vagotomized animals consuming familiar laboratory chow with those consuming a novel diet. In contrast to the novel diets, learned aversions did not develop to the familiar chow, and hypophagia was less persistent and severe. It is concluded that learned food aversions can contribute to the appetite and weight loss exhibited by vagotomized animals. Consideration of the conditions under which these aversions arise after vagotomy surgery may allow for the design of studies so as to minimize the aversions and thereby separate these nonspecific effects from direct regulatory deficits produced by vagotomy.

Animals↗
PubMed2006

Cortical substrates for exploratory decisions in humans.

Decision making in an uncertain environment poses a conflict between the opposing demands of gathering and exploiting information. In a classic illustration of this 'exploration-exploitation' dilemma, a gambler choosing between multiple slot machines balances the desire to select what seems, on the basis of accumulated experience, the richest option, against the desire to choose a less familiar option that might turn out more advantageous (and thereby provide information for improving future decisions). Far from representing idle curiosity, such exploration is often critical for organisms to discover how best to harvest resources such as food and water. In appetitive choice, substantial experimental evidence, underpinned by computational reinforcement learning (RL) theory, indicates that a dopaminergic, striatal and medial prefrontal network mediates learning to exploit. In contrast, although exploration has been well studied from both theoretical and ethological perspectives, its neural substrates are much less clear. Here we show, in a gambling task, that human subjects' choices can be characterized by a computationally well-regarded strategy for addressing the explore/exploit dilemma. Furthermore, using this characterization to classify decisions as exploratory or exploitative, we employ functional magnetic resonance imaging to show that the frontopolar cortex and intraparietal sulcus are preferentially active during exploratory decisions. In contrast, regions of striatum and ventromedial prefrontal cortex exhibit activity characteristic of an involvement in value-based exploitative decision making. The results suggest a model of action selection under uncertainty that involves switching between exploratory and exploitative behavioural modes, and provide a computationally precise characterization of the contribution of key decision-related brain systems to each of these functions.

Choice Behavior↗
PubMed2005

Contemporary dental practice in the UK: demographic data and practising arrangements.

OBJECTIVES: To investigate, by questionnaire, various aspects of primary dental care provision in the North West of England and Scotland. METHOD: A questionnaire containing 79 questions was sent to 1,000 practitioners, selected at random, in the North West of England and Scotland. Non-responders were sent another questionnaire after a period of 4 weeks had elapsed. RESULTS: Overall a response rate of 70% was achieved. The majority of practitioners were practice principals (65%), working in a group NHS practice (80%) located in a city or town centre (49%). On average 10-20 patients were treated each session with fewer patients treated per session under private arrangements. Many practitioners were found to lack hygienist support (44%) and to employ unqualified dental nurses (82%). Younger practitioners were more likely than senior colleagues to have access to up-to-date computers whilst 37% and 74% of respondents never used CAL programmes or magnification respectively. Contemporary cross-infection control standards were used by the majority of practitioners, although 3% of practitioners reported only autoclaving their handpiece once a day. CONCLUSIONS: The majority of practitioners, involved in this study, worked under National Health Service (NHS) regulations as principals in a group practice where the workload was greater than the private/independent sector. Contemporary cross-infection procedures were used routinely. In contrast computer-aided learning programmes and magnification were not used routinely. The practitioners in this study employed significant numbers of unqualified dental nurses.

Anesthesia, Dental↗
PubMed2001

Lack of tissue glucocorticoid reactivation in 11beta -hydroxysteroid dehydrogenase type 1 knockout mice ameliorates age-related learning impairments.

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) intracellularly regenerates active corticosterone from circulating inert 11-dehydrocorticosterone (11-DHC) in specific tissues. The hippocampus is a brain structure particularly vulnerable to glucocorticoid neurotoxicity with aging. In intact hippocampal cells in culture, 11beta-HSD-1 acts as a functional 11beta-reductase reactivating inert 11-DHC to corticosterone, thereby potentiating kainate neurotoxicity. We examined the functional significance of 11beta-HSD-1 in the central nervous system by using knockout mice. Aged wild-type mice developed elevated plasma corticosterone levels that correlated with learning deficits in the watermaze. In contrast, despite elevated plasma corticosterone levels throughout life, this glucocorticoid-associated learning deficit was ameliorated in aged 11beta-HSD-1 knockout mice, implicating lower intraneuronal corticosterone levels through lack of 11-DHC reactivation. Indeed, aged knockout mice showed significantly lower hippocampal tissue corticosterone levels than wild-type controls. These findings demonstrate that tissue corticosterone levels do not merely reflect plasma levels and appear to play a more important role in hippocampal functions than circulating blood levels. The data emphasize the crucial importance of local enzymes in determining intracellular glucocorticoid activity. Selective 11beta-HSD-1 inhibitors may protect against hippocampal function decline with age.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1996

Mice lacking the gene encoding tissue-type plasminogen activator show a selective interference with late-phase long-term potentiation in both Schaffer collateral and mossy fiber pathways.

The gene encoding tissue-type plasminogen activator (t-PA) is an immediate response gene, downstream from CREB-1 and other constitutively expressed transcription factors, which is induced in the hippocampus during the late phase of long-term potentiation (L-LTP). Mice in which the t-PA gene has been ablated (t-PA-/-) showed no gross anatomical, electrophysiological, sensory, or motor abnormalities but manifest a selective reduction in L-LTP in hippocampal slices in both the Schaffer collateral-CA1 and mossy fiber-CA3 pathways. t-PA-/- mice also exhibit reduced potentiation by cAMP analogs and D1/D5 agonists. By contrast, hippocampal-dependent learning and memory were not affected in these mice, whereas performance was impaired on two-way active avoidance, a striatum-dependent task. These results provide genetic evidence that t-PA is a downstream effector gene important for L-LTP and show that modest impairment of L-LTP in CA1 and CA3 does not result in hippocampus-dependent behavioral phenotypes.

Animals↗
PubMed2007

A role for reactive oxygen/nitrogen species and iron on neuronal synaptic plasticity.

A great body of experimental evidence collected over many years indicates that calcium has a central role in a variety of neuronal functions. In particular, calcium participates in synaptic plasticity, a neuronal process presumably correlated with cognitive brain functions such as learning and memory. In contrast, only recently, evidence has begun to emerge supporting a physiological role of reactive oxygen (ROS) and nitrogen (RNS) species in synaptic plasticity. This subject will be the central topic of this review. The authors also present recent results showing that, in hippocampal neurons, ROS/RNS, including ROS generated by iron through the Fenton reaction, stimulate ryanodine receptor-mediated calcium release, and how the resulting calcium signals activate the signaling cascades that lead to the transcription of genes known to participate in synaptic plasticity. They discuss the possible participation of ryanodine receptors jointly stimulated by calcium and ROS/RNS in the normal signaling cascades needed for synaptic plasticity, and how too much ROS production may contribute to neurodegeneration via excessive calcium release. In addition, the dual role of iron as a necessary, but potentially toxic, element for normal neuronal function is discussed.

Animals↗