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Memory deficits in Alzheimer's patients: a comprehensive review.

Despite considerable experimental work on Alzheimer's disease (AD), the underlying cognitive mechanisms as well as the precise localization of neuropathological changes critical for memory loss remains undefined. A review of the neuropsychological literature on long-term memory deficits in AD patients suggests that AD patients display (a) a pervasive deficit of explicit memory, (b) a partial deficiency of implicit memory for verbal and visuoperceptual material (as measured by repetition priming procedures), and (c) a substantial sparing of implicit memory for visuomotor skills. The explicit memory loss is likely a result of encoding as well as consolidation difficulties. A faulty lexical-semantic knowledge structure appears responsible for deficient repetition priming effects. Since neuropathological changes diffusely affect the brain of AD patients, establishing a clear relationship between localization of cerebral lesions and memory deficits is particularly difficult. Nevertheless, data suggest that extensive involvement of the hippocampal-amygdala complex plays a major role in explicit memory loss. Damage to associative cortical areas likely is involved in repetition priming deficits. The relative integrity of primary motor and sensory cortical areas and of the basal ganglia likely subsume, by contrast, the normal learning of visuomotor skills.

Aged↗

Long-term potentiation in the rat hippocampal CA1 region is inhibited selectively at the acquisition stage of discriminatory avoidance learning.

Long-term potentiation (LTP) of hippocampal synaptic efficacy has been regarded as a synaptic model of learning and memory. We examined whether the induction of LTP in the hippocampal regions was altered with the advance of discriminatory avoidance learning. Evoked potentials in the CA1 region or dentate gyrus were recorded before and after tetanic stimulation in anesthetized rats which had been given training sessions 24 h before. LTP of the amplitude of population spikes and the slope of excitatory postsynaptic potentials recorded in the CA1 region was smaller in rats at a learning stage 24 h after the avoidance rate had first been significantly increased than in naive rats. The magnitude of LTP was not altered in rats which had been exposed to the first training session or in those which had received overtraining. The inhibition of LTP in the CA1 was neither due to stress accompanied with training nor liberation from the stress by learning avoidance response. In contrast, LTP induced in the dentate gyrus was rather enhanced at the learning stage when LTP in the CA1 was inhibited. The results suggest that the acquisition of discriminatory avoidance learning selectively inhibits LTP in the hippocampal CA1 region.

Animals↗

Hormones and regional brain blood flow.

Acute effects of the hormones, estradiol-17beta and alphaMSH, and of neonatal pretreatment with alphaMSH on the flow of blood to regions of the brains of conscious adult rats have been determined with an indicator distribution technique. As previously reported, flows were reduced in most areas within 10 min after intravenous administration of alphaMSH; only the occipital cortex was spared. Though these effects were transitroy for most areas, perfusion of pons and medulla, cerebellum, hippocampus and parietal cortex was still low by 20 min. However, pretreatment with alphaMSH during infancy led to persistent behavioral changes which were not accompanied by flow differences. Assuming that flow changes reflect functional changes, the rapid responses to alphaMSH suggest an explanation for the effects of this hormone on visual learning and on the determination of subsequent learning behavior. By contrast, estradiol, within 10 min after injection, increased flow to most regions of the brain, especially the frontal cortex, hippocampus, basal ganglia and cerebellum; females were more affected than males. Flow changes were greater than those elicited by more obvious behavior-modifying drugs. Compared to alphaMSH, the flow data for estradiol suggest a physiologic basis for a behavioral effect which is likely to be different yet, perhaps, equally profound.

Animals↗

Effects of alcohol consumption on the prevention and alleviation of stress-reactions.

Alcohol's Stress-Response-Dampening (SRD) effect has been the subject of much research, but little has been done to examine the effects of drinking alcohol after experiencing a stressor (Stress-Response-Recovery; SRR). In this study, 65 male and 65 female moderate or heavy drinking undergraduates were randomly assigned (with equal numbers of each sex per group) to 1 of 13 groups. Six experimental conditions were used to compare alcohol's SRD and SRR effects with two doses (moderate: .75 ml/kg; low: .33 ml/kg) and a placebo, and seven control conditions were used to measure the effects of the stressor (uncontrollable aversive noise) and the alcohol doses alone on the dependent measures. The major dependent variable was escape learning in a human shuttle box. In the SRD conditions, subjects who drank a moderate dose of alcohol learned to escape faster than those drinking the low dose or placebo. However, in the SRR conditions, subjects in the placebo group did not show escape learning deficits, in contrast to the impaired performance of subjects in the two alcohol groups. These results suggest a complex alcohol-stress relationship in which timing, dose, and expectations about alcohol lead to differential SRD and SRR effects.

Adult↗

Ex vivo MRI in extracorporeal liver surgery.

Extracorporeal resection of hepatic tumors that were considered inoperable in the past is now possible in selected cases. Such procedures require high-quality preoperative images for the exact delineation of the tumor extent and for an optimal planning of the line of parenchymal division. In-vivo CT and MRI can not always depict the tumor adequately. In such cases, ex-vivo MRI may be a useful additional technique. It combines a high spatial resolution with the best possible soft tissue contrast, as was learned from previous studies on donor livers destined for transplantation. Ex-vivo MRI favours both a sufficiently radical resection as well as sufficient hepatic functional reserve to be present for reimplantation. A case history is reported together with details on the technical procedure.

Adenocarcinoma↗

Long-term changes in fear conditioning and anxiety-like behavior following nicotine exposure in adult versus adolescent rats.

Adolescent nicotine exposure is associated with long-term use, and it has been suggested that this vulnerability to addiction may relate to lasting anxiogenic effects of the drug. However, few studies have addressed long-term effects of adolescent nicotine, and fewer yet have compared adolescent to adult exposure. Male and female Long-Evans rats continuously received nicotine bitartrate or sodium tartrate via osmotic mini-pumps over 15 days either during adolescence (p28-42) or adulthood (p85-99). Initial nicotine dose (free base) was either low (1 mg/kg/day) or high (2 mg/kg/day). Open field behavior and fear conditioning were assessed in adulthood, 1 month post-dosing. Animals pretreated with nicotine during adolescence showed less center time in a novel open field than sham controls. Conversely, the two nicotine doses differentially affected fear conditioning. Animals pretreated with low nicotine during adolescence demonstrated superior acquisition of the task compared to sham control animals; however, unlike either high nicotine-pretreated or sham control animals, they failed to extinguish the learned behavior. In contrast, animals pretreated during adulthood did not behave significantly different from sham controls on either task. Overall, nicotine-pretreatment during adolescence induced effects on behaviors related to fear and anxiety in adulthood, while comparable pretreatment during adulthood failed to produce significant residual effects.

Age Factors↗

A limit on behavioral plasticity in speech perception.

It is well attested that we perceive speech through the filter of our native language: a classic example is that of Japanese listeners who cannot discriminate between the American /l/ and /r/ and identify both as their own /r/ phoneme (Goto. H., 1971. Neuropsychologia 9, 317-323.). Studies in the laboratory have shown, however, that perception of non-native speech sounds can be learned through training (Lively, S.E., Pisoni, D.B., Yamada, R.A., Tohkura, Y.I., Yamada, T., 1994. Journal of the Acoustical Society of America 96 (4), 2076-2087). This is consistent with neurophysiological evidence showing considerable experience-dependent plasticity in the brain at the first levels of sensory processing (Edeline, J.-M., Weinberger, N.M., 1993. Behavioral Neuroscience 107, 82-103; Merzenich, M.M., Sameshima, K., 1993. Current Opinion in Neurobiology 3, 187-196; Weinberger, N.M., 1993. Current Opinion in Neurobiology 3, 577-579; Kraus, N., McGee, T., Carrel, T.D., King, C., Tremblay, K., Nicol, T., 1995. Journal of Cognitive Neuroscience 7 (1), 25-32). Outside of the laboratory, however, the situation seems to differ: we here report is study involving Spanish-Catalan bilingual subjects who have had the best opportunities to learn a new contrast but did not do it. Our study demonstrates a striking lack of behavioral plasticity: early and extensive exposure to a second language is not sufficient to attain the ultimate phonological competence of native speakers.

Analysis of Variance↗

Endoscopic band ligation for non-variceal non-ulcer gastrointestinal hemorrhage.

BACKGROUND: There is no consensus as to the best treatment for non-variceal, non-ulcer gastrointestinal hemorrhage. Endoscopic band ligation is an inexpensive, readily available, and easily learned technique in contrast to conventional thermal methods of endoscopic hemostasis. We present the preliminary results of an open trial using endoscopic band ligation for non-variceal, non-ulcer bleeding in the gastrointestinal tract. METHODS: Eighteen patients were treated by band ligation between June 1996 and November 1997. The lesions treated were: arteriovenous malformations in 10, Dieulafoy's lesions in 4, Mallory-Weiss tear in 2, and post-colonic polypectomy bleeding in 2. RESULTS: Endoscopic band ligation was successful in 17 of 18 cases, with a follow-up period ranging from 2 to 18 months. The remaining case, a duodenal Dieulafoy's lesion, bled again at 24 hours but was successfully treated by adrenalin injection. CONCLUSIONS: Endoscopic band ligation is effective for non-variceal, non-ulcer bleeding. It has the advantage of ease of use and is relatively inexpensive.

Aged↗

Acute and long-term consequences of single MDMA administration in relation to individual anxiety levels in the rat.

Our previous work has shown that normal male Wistar rats can differ systematically in their behavioral response to the elevated plus-maze (EPM), where animals with high (HA) or low anxiety (LA) levels can be identified based on the percentage of time spent in the open arms. These animals also differ in other behavioral tests (e.g. active avoidance), and in their serotonin levels in the ventral striatum. Here, we tested whether such HA and LA rats might respond differently to the amphetamine analogue 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). This drug can affect psychomotor activation and anxiety; effects which are probably due to its pronounced serotonergic and dopaminergic impacts in the rat brain. Based on a routine screening procedure in the plus-maze, male Wistar rats were divided into HA and LA sub-groups, in which rectal temperature was measured. Thirty minutes after the i.p. injection of MDMA (7.5 or 15 mg/kg) or vehicle, they were again tested in the plus-maze. During the next 3 weeks, the animals underwent further behavioral tests (plus-maze, open field, active avoidance, forced swimming) to test for possible long-term consequences of MDMA. Rectal temperature was found to be higher in LA than HA rats and was especially increased with the higher dose of MDMA (15 mg/kg). In the acute plus-maze test, the lower dose of MDMA led to an anxiogenic-like profile, whereas the higher dose led to an anxiolytic-like profile, both in HA and LA rats. Possible long-term consequences of MDMA were only tested with 7.5 mg/kg MDMA, since the 15 mg/kg dose led to a high level of lethality. The analysis of open field, plus-maze (performed after 9-12 days), and forced swimming behavior (performed after 20-21 days) did not provide indications for lasting effects of MDMA. In contrast, active avoidance learning was impaired in LA- but not HA-rats treated with MDMA. A single injection of MDMA does not only have acute effects on anxiety and psychomotor activation, but can also have some prolonged or delayed task-dependent behavioral consequences. The detection of such sequels can require that individual differences are taken into account and here, determining anxiety levels in the EPM seems to serve as a useful approach.

Analysis of Variance↗

Priming effects in picture fragment completion: support for the perceptual closure hypothesis.

The perceptual closure hypothesis says that priming will be optimum when just enough information is available in the prime to support closure. Across 5 experiments, a moderately complete fragmented image (Level 4) produced more priming than an almost complete (Level 7) or a very incomplete (Level 1) fragmented image. Only Level 4 priming was improved by increases in prime duration and by showing the prime again after Ss attempted to identify it. Explicit memory played little role in primed fragment completion except for Level 1 priming, in which specific fragment memory was responsible for the entire effect. In contrast, true perceptual learning was shown to be responsible for Level 4 and Level 7 priming. These priming effects cannot be accounted for by the transfer-appropriate procedures approach of Roediger and his colleagues because Level 1 priming produced less transfer to Level 1 identification at test than Level 4 priming did.

Adult↗

Influence of affective meaning on memory for contextual information.

In 4 experiments, the authors investigated the influence of the affective meaning of words on memory for 2 kinds of contextual features that differ in the amount of effortful processes they require to be encoded in memory (i.e., color and spatial location). The main results showed that memory for color, in which words were typed, was better for emotional than for neutral words, but only when color information was learned incidentally. In contrast, spatial location of the words was better remembered for emotional than for neutral words whatever the encoding conditions (intentional vs. incidental). It is suggested that the influence of affective meaning on context memory may involve an automatic attraction of attention to contextual features associated with emotional words.

Adult↗

Is there a maternally induced immunological imprinting phase à la Konrad Lorenz?

In mammals, IgG antibodies are transferred from mothers to the offspring. Since these maternal antibodies result mainly from thymus-dependent immune responses which have undergone immune maturation through somatic hypermutations, they represent the highest quality of the collective maternal immunological experience. Maternal antibodies not only confer passive immunity as long as the newborn's immune system has not fully developed, but also exert an active stimulation as indicated by their regulatory influence on isotype expression, long-term idiotypic alterations, determination of the adult B and T cell repertoire, induction of antigen reactive IgM as well as an affinity enhancement of a proportion of early primary antibodies. The fact that several of these features can only be induced during limited sensitive periods shortly after birth is reminiscent of the behavioural imprinting as defined by Konrad Lorenz. We therefore propose that during early ontogeny there is an immunological imprinting phase with characteristics analogous to behavioural imprinting: (i) the internal imprinting effect is induced by external signals, (ii) in contrast to normal learning, immunological imprinting is also only possible during certain development phases and (iii) it is characterised by an (almost) irreversible result. Hence, if particular immunological experiences are only possible during such sensitive phases, maternal immunoglobulins and consequently the mother's immunological experience is of prime importance for the start of the ontogenetic development of the immune system.

Animals↗

Mallory-Weiss syndrome with severe bleeding: treatment by endoscopic ligation.

There is no consensus as to the best treatment for Mallory-Weiss tears with severe bleeding. Endoscopic ligation is an inexpensive, readily available, and easily learned technique, in contrast to conventional thermocoagulation or hemoclipping. To evaluate the utility of endoscopic ligation, we performed this technique during emergency endoscopy to treat severe bleeding from Mallory-Weiss tears in four patients in our hospital with continuous active bleeding from Mallory-Weiss tears. The patients were all male with an average age of 40.5 years. Symptoms associated with increased intra-abdominal pressure, including retching and vomiting were reported by all patients. The bleeding points were aspirated and controlled by endoscopic ligation, and complete hemostasis was achieved in all cases. We conclude that endoscopic ligation is easy to perform and may provide an alternative treatment for severe bleeding from Mallory-Weiss tears.

Adult↗

Training in GI endoscopy: can we objectively predict the performance of trainees? A prospective correlation study.

BACKGROUND: No objective criteria have hitherto been available for assessing the individual talents and skills of trainees involved in GI endoscopy. The aim of our study was to compare the correlation of various psychological, psychomotor and cognitive tests (psy-tests) and of the subjective assessment of the trainer (expert assessment) at the beginning of the training with the objective performance of the trainees at the end of a one-week training period in upper GI endoscopy. METHODS: In a prospective study including 12 endoscopic centers, a total of 58 participants without any prior endoscopic experience were analyzed. During a practical training week in each center with the "Erlangen Endo-Trainer," an assessment using a "score card" protocol was used as reference method. Prior to the start of the training, various psy-tests (personality test, vigilance endurance test, test of spatial thinking and two tests of sensorimotor coordination) as well as assessment of the trainer were obtained. These parameters were compared with a blinded analysis of the performance at the end of the training. RESULTS: There was significant overall improvement during the training course. Multiple logistic regression analysis revealed that testing sensorimotoric coordination was significantly associated with defined improvement margins (odds ratio 11.46, p = 0.035). An expert's judgment on the prognosis correlated also significantly with the trainee's improvement (OR = 41.46; p = 0.018). Self-assessments were not significantly associated with performance or progress. CONCLUSIONS: Sensorimotoric tests may provide a reliable prediction of the trainee's learning progress. In contrast to self-assessment, the judgement of an experienced endoscopist provides the best guidance for the young candidate endoscopists prior to the start of his/her endoscopic training program.

Attention↗

A neuro-cognitive visual system for object recognition based on testing of interactive attentional top-down hypotheses.

We propose an extension of a systemic model for object recognition formulated by Rybak et al (1998 Vision Research 38 2387-2400) which is based on the functional organisation of the visual systems in primate brains. In contrast to the learning and recognition scheme of Rybak et al we do not assume a behavioural paradigm, i.e. a visuomotor programmed scanpath that determines the sequence of foveation on the different parts of the object. As in the basis architecture of Rybak et al, the system modules are separated into 'what'-like subsystems corresponding to the ventral occipito-inferotemporal visual path and 'where'-like complexes analogous to the dorsal occipito-parietal visual path. The 'what' system analyses local features in the actual foveation as in Rybak et al. But, in our case, the 'where' memory, instead of programming a behavioural scanpath, scores the spatial relationship between successive fixation and the spatial relationship between the associated main edges. The recognition is based on the identification of parts and their spatial relationship. This gives the learning and recognition mechanisms more flexibility in the sense that, for recognising an object, several different fixation sequences may be accepted.

Cognition↗

A picture is worth more than a thousand words: enhancement of a pre-exam telephone consultation in dermatology with digital images.

OBJECTIVE: In addition to the assessment and the management of patients with skin diseases, a considerable portion of dermatology residency involves examining clinical images and generating differential diagnoses from these images. This training, though helpful for recognizing manifestations of rare disorders, goes unused by most practicing dermatologists after certification. In contrast, dermatology residents learn and master verbal descriptions of skin diseases and continue to use this skill throughout their careers. However, problems arise when a dermatologist is not available and a non-dermatologist attempts to verbally describe a skin condition. An accurate description of a cutaneous disorder can facilitate effective triage management of a patient when a dermatologist is not available. Unfortunately, an inaccurate description by the referring provider can lead to diagnostic bias and ineffective, or even harmful, initial treatment. In recent years, digital photography has facilitated the electronic transfer of clinical images over distances. However, despite the promise that this technique shows in providing teledermatologic services to specialty-underserved areas and the availability of low-cost digital cameras, telephone consultation is still the standard of care when a dermatologist is not available. The purpose of this study is to compare the reliability of dermatologic consultations that use the telephone with that of dermatologic consultations that use both the telephone and digital images. DESCRIPTION: After patient approval, an acute care provider randomly assigned patients with skin disorders of unclear etiology to two groups, with and without digital images. The acute care provider then performed an exam and took the patient's history. Telephone data, with or without digital images, were then presented to the consulting dermatologist, who formulated a pre-physical exam differential diagnosis and treatment plan. The consulting dermatologist immediately examined the patient in person and refined the diagnosis and management. The confidence in diagnosis, both before and after the in-person exam, was compared in the patient group with digital images and in the patient group without digital images using a five-point scale (1 = no confidence, 5 = most confident). DISCUSSION: The consulting dermatologist evaluated 12 patients (six with digital images and six without digital images). In the patient group with digital images, the consulting dermatologist's confidence in diagnosis varied very little from before to after the in-person exam (from no change in five cases to a one-point increase in the sixth case). In the patient group without digital images, the consulting dermatologist's confidence level increased significantly from before to after the in-person exam. This led to therapy changes for three of the six patients in the patient group without digital images, versus two of the six patients in the patient group with digital images. This study indicates that an acute care provider's verbal description of a skin condition may be less reliable compared with a provider's verbal description combined with digital images. Telephone-only descriptions may also lead to management discrepancies more frequently than telephone descriptions with digital images. This has at least two implications for medical education: (1) need for support of formal teaching of the language of dermatology to non-dermatologists and (2) justification of the time spent in two-dimensional clinical image interpretation by dermatology residents in light of digital image technology.

Dermatology↗

How money matters for young children's development: parental investment and family processes.

This study used data from the Panel Study of Income Dynamics and its 1997 Child Development Supplement to examine how family income matters for young children's development. The sample included 753 children who were between ages 3 and 5 years in 1997. Two sets of mediating factors were examined that reflect two dominating views in the literature: (1) the investment perspective, and (2) the family process perspective. The study examined how two measures of income (stability and level) were associated with preschool children's developmental outcomes (Woodcock-Johnson [W-J] Achievement Test scores and the Behavior Problem Index [BPI]) through investment and family process pathways. Results supported the hypothesis that distinct mediating mechanisms operate on the association between income and different child outcomes. Much of the association between income and children's W-J scores was mediated by the family's ability to invest in providing a stimulating learning environment. In contrast, family income was associated with children's BPI scores primarily through maternal emotional distress and parenting practices. Level of income was associated with W-J letter-word scores and income stability was associated with W-J applied problem scores and BPI, even after all controls were included in the models.

Attitude↗

Smoking: a special need?

The smoking behaviour of 665 children aged 12-15 years with special educational needs was compared with that of a control group of 842 children in mainstream education. Each child was interviewed using a structured questionnaire and reported smoking behaviour was validated against scores on a carbon monoxide monitor. We identified as the most at risk group children with emotional and behavioural disorders. They had the highest smoking rates and were the heaviest smokers. In contrast, children with learning difficulties had slightly lower smoking rates than those of the control. There were significant associations between the children's smoking behaviour and the smoking behaviour of siblings and 'other adults' in the household, belonging to single parent families, low self-esteem and large friendship groups. The reported smoking rates of the families of both groups of special needs children was found to be considerably higher than that in the control group or in the general population.

Achievement↗