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Building new motor responses: eyelid conditioning revisited.

Neural processes underlying memory and learning should be studied under the best possible physiological conditions - namely, in alert behaving animals. The classical conditioning of the nictitating membrane and eyelid response is a widely used experimental model for studying the neural bases of motor learning in mammals. Nevertheless, information is still needed on the functional aspects, taking place simultaneously in different cerebral structures, that underlie acquisition, extinction and recall of new motor and cognitive abilities. Here, we review recent data on the neural activity generated in selected brain sites (facial motor nuclei, deep cerebellar nuclei and the hippocampus) in simultaneity with the process of learning. The use of modern technologies for the proper recording of eyelid movements, for the identification of the recorded units, and for the activation of selective synaptic processes during the learning situation enables a precise redefinition of the role played by these neural structures in such associative learning. This review is part of the TINS special issue on The Neural Substrates of Cognition.

Animals↗

Young kittens can learn complex visual pattern discriminations.

Kittens begin to display visually elicited responses shortly after eye opening. The pupillary reflex, optokinetic response, visual placing and avoidance of the deep side of the visual cliff all appear between the second and fifth weeks of life, and evidence of visual learning in homing behaviour has been described at the same early age. However, an attempt to elicit pattern preferences in kittens of this age (usually considered the easiest way to demonstrate discriminatory behaviour in immature organisms) was unsuccessful, evidently because such kittens show little spontaneous visual interest. This is surprising in view of electrophysiological findings which emphasise the importance of the fourth to sixth weeks in the development of cortical feature-analysing mechanisms; perhaps the stimulus-seeking methodology of Dodwell et al. is anappropriate for the visual modality at such an early age. Recently, visual acuity measurements have been reported for kittens as young as 30 d of age using a contour versus no-contour discrimination on a modified Lashley jumping stand. With this technique we have now trained kittens of under 50 d of age to perform more complex pattern discriminations.

Age Factors↗

Medical students' learning of anatomy: memorisation, understanding and visualisation.

INTRODUCTION: There is much subjective discussion, but few empirical data that explore how students approach the learning of anatomy. AIMS: Students' perceptions of successful approaches to learning anatomy were correlated with their own approaches to learning, quality of learning and grades. METHODS: First-year medical students (n = 97) studying anatomy at an Australian university completed an online survey including a version of the Study Process Questionnaire (SPQ) that measures approaches to learning. The quality of students' written assessment was rated using the Structure of Observed Learning Outcomes (SOLO) taxonomy. Final examination data were used for correlation with approaches and quality of learning. RESULTS: Students perceived successful learning of anatomy as hard work, involving various combinations of memorisation, understanding and visualisation. Students' surface approach (SA) scores (mean 30 +/- 3.4) and deep approach (DA) scores (mean 31 +/- 4.2) reflected the use of both memorisation and understanding as key learning strategies in anatomy. There were significant correlations between SOLO ratings and DA scores (r = 0.24, P < 0.01), between SA scores and final grades (r = - 0.30, P < 0.01) and between SOLO ratings and final grades (r = 0.61, P < 0.01) in the subject. CONCLUSIONS: Approaches to learning correlate positively with the quality of learning. Successful learning of anatomy requires a balance between memorisation with understanding and visualisation. Interrelationships between these three strategies for learning anatomy in medicine and other disciplines require further investigation.

Anatomy↗

The approaches to learning of students in a traditional and in an innovative problem-based medical school.

The way in which students approach their learning is dependent on a variety of factors including the characteristics of the departments and teaching to which they are exposed. These factors appear to influence whether the students adopt a surface, deep or strategic approach. In order to explore further the relationship between educational context and approach to learning, a comparison was made between students attending a traditional medical school and those attending a problem-based medical school. The results showed marked differences, with the problem-based school being higher on deep approach and lower on surface approach than the traditional school. This study provides one of the first pieces of evidence of a difference between students in the two types of medical school which can be directly attributed to the educational environment. Students in the problem-based school appear to have an approach to learning which more closely approximates the aims of most medical schools. The results provide support for the philosophies and strategies of the problem-based schools.

Australia↗

Safe evolution towards routine off-pump coronary artery bypass: negotiating the learning curve.

OBJECTIVE: Off-pump coronary artery bypass (OPCAB) hopes to avoid morbidity associated with cardiopulmonary bypass, improving clinical outcomes. Yet its technical difficulty and unfamiliarity raise concern that adoption of OPCAB might be associated with poorer outcomes during each surgeon's 'learning curve'. We examined trends in patient selection over time as a single surgeon's practice evolved to routine OPCAB. METHODS: Between 10-1-96 and 12-31-01, 1479 consecutive patients had isolated coronary artery bypass grafting (CABG). Clinical data were gathered prospectively and reviewed retrospectively. Trends in adoption of OPCAB and clinical outcomes were examined. RESULTS: There were 756 OPCAB and 723 CABG/cardiopulmonary bypass patients. The practice evolved from 90% conventional CABG to 93% OPCAB. An abrupt transition coincided with evolution of techniques to expose the obtuse marginal arteries, and improvements in suction-based coronary stabilizers. Mortality was 1.0% for the off-pump group and 2.1% for the on-pump group. Careful patient selection helped maintain acceptable outcomes during the 'learning curve'. Patients with depressed left ventricular ejection fraction, left main disease, and complex three vessel disease were excluded from OPCAB until significant experience (>200 cases) was attained. Presently, all isolated coronary bypass cases are candidates for OPCAB except patients with ischemic ventricular arrhythmias, those in cardiac arrest, and those for whom previous left pneumonectomy or deep pectus excavatum prevent rightward mobilization of heart. CONCLUSIONS: Despite a significant learning curve, evolution to routine OPCAB can be achieved while maintaining good patient outcomes. The development of specialized techniques, coronary stabilizers, and apical suction devices allows the application of OPCAB to virtually all coronary bypass patients, as surgeon experience matures.

Aged↗

Parkinson's Disease: Surgical Options.

Surgical therapy for Parkinson's disease (PD) has been a treatment option for over 100 years. Advances in the knowledge of basal ganglia physiology and in techniques of stereotactic neurosurgery and neuroimaging have allowed more accurate placement of lesions or "brain pacemakers" in the sensorimotor regions of target nuclei. This, in turn, has led to improved efficacy with fewer complications than in the past. Currently, bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi) is the preferred option (and is approved by the US Food and Drug Administration) for the surgical treatment of PD. The most important predictors for outcome for DBS for PD are patient selection and electrode location. Patients should have a documented preoperative improvement from dopaminergic medication of at least 30% in the patient's Unified Parkinson's Disease Rating Scale motor disability scores. A levodopa challenge may be needed to document the best "on" state. Dementia or active cognitive decline must be excluded. Active psychiatric disease should be treated preoperatively. Patients should be motivated, with good support systems, and committed to the postoperative management of DBS therapy. Deep brain stimulation should be considered when the patient begins to experience dyskinesia and on-off fluctuations despite optimal medical therapy. Deep brain stimulation is not a good option at the final stages of the disease because of the increased incidence of dementia and severe comorbidity. The DBS electrode should be placed in the sensorimotor region of the GPi or STN. Subthalamic nucleus and GPi DBS can improve all motor aspects of PD, as well as predictable "on" time, without dyskinesia or fluctuations. On average, STN DBS results in a greater reduction of dopaminergic medication compared with GPi DBS. Because of the smaller size of the target region, the pulse generator battery life is longer with STN then with GPi DBS. Deep brain stimulation programming is a skill that is readily learned and may be required of all neurologists in the future. Emerging surgical therapies are restorative, and they aim to replace or regenerate degenerating dopaminergic neurons. These include embryonic mesencephalic tissue transplantation, human embryonic stem cell transplantation, and gene-derived methods of intracerebral implantation of growth factors and dopamine- producing cell lines. It will be important to determine whether DBS, if performed before the onset of motor response complications to medical therapy, may prevent this stage of disease altogether or delay it for a significant period of time. The same question applies to the future with restorative therapy.

Journal Article↗

Effects of transient cerebral ischemia on the hippocampal dentate theta (theta) profile in the acute rat: a study 4-5 months following recirculation.

This study mainly describes the long-term effects of 20 min of cerebral ischemia on the profile of the presumed cholinergic theta rhythm in the rat dorsal hippocampal formation during ether anesthesia and injection of the muscarinic agonist agent arecoline. The experimental data were collected 4-5 months after ischemia. They show that ischemia results in a statistically significant reduction in both superficial and deep theta recorded from the CA1 area of the hippocampus and the dentate gyrus, respectively. Amplitude reduction is similar for both rhythms and co-varies positively with the extent of CA1 stratum pyramidale damage which, from light microscope observation, appeared to be the major neuroanatomical consequence of ischemic insult in the dorsal hippocampal formation. The medial septal nucleus-diagonal band of Broca complex involved in theta generation did not suffer visible anatomical damage. Moreover, no significant alteration in the spatial distribution and the density of hippocampal dentate acetylcholinesterase reaction product was seen in ischemic animals. These histological data were statistically confirmed by computerized image analysis. Finally, this is the first investigation to show that transient interruption of cerebral blood flow results in a long-lasting alteration of theta rhythm which is probably the major aspect of the basic activity of the hippocampal formation. Thus, the present findings obtained in the acute rat at 4-5 months postischemia confirm and extend, in most respects, our previous results collected in the chronic animal 2-29 days following 4-vessel occlusion. Possible significance of these findings for the hypothesis of the dependent generation sites of superficial and deep thetas in the hippocampus assumed to be crucial in learning and memory, is discussed.

Acetylcholinesterase↗

Approaches to learning and academic achievement of Filipino students.

Research has shown that a critical variable in determining academic achievement in different cultures and educational systems is approaches to learning. In this study, the author sought to determine whether this variable influences academic achievement among Filipino college students. The Learning Process Questionnaire (LPQ; J. B. Biggs, 1987) was used to assess approaches to learning. The results indicated that (a) the LPQ was a valid instrument to assess the learning approaches of non-low-achieving Filipino college students; (b) the Deep and Achieving subscale scores of the LPQ were positively related to academic achievement even when the effects of school ability and prior academic achievement were controlled; and (c) with some slight exceptions, the relationship between the LPQ scale scores and academic achievement were generally similar between male and female Filipino students. Implications for the study of student approaches to learning in different cultures and educational systems are discussed.

Adolescent↗

New horizons in ambulatory electroencephalography.

Since its inception 30 years ago, AEEG has continued to evolve--from four-channel tape recorders to 32-channel digital recorders with sophisticated automatic spike and seizure detection algorithms. AEEG remains an important tool in epilepsy evaluation. In the near future, smaller, faster, and more sophisticated AEEGs will be developed. Seizure detection/anticipation systems will allow the wearer to be forewarned of a seizure so that appropriate safety measures can be taken. With further refinement in our understanding of nonlinear dynamic analysis to define the pre-ictal state, AEEG will be coupled with an accurate seizure anticipation device in a closed-loop system, providing a time window during which therapeutic intervention can occur, to prevent a seizure. The therapeutic intervention will most likely involve vagus nerve or deep brain stimulation. An alternative is that the patient may learn to recognize early symptoms of the pre-ictal state and use behavioral biofeedback interventions to avoid a clinical seizure. In order to achieve convenient ambulatory recording and seizure detection that could realistically improve the lives of patients with refractory epilepsy, the process of miniaturization of such a device to a convenient size must be accomplished. One of the aspects of epilepsy that patients find most frustrating, and that most limits activities, is the vulnerability to sudden unexpected incapacitation due to the occurrence of a seizure. With miniaturization of AEEG and seizure anticipation technology, and advancements in our ability to identify the transition from pre-ictal to ictal state, there is realistic hope that patients with refractory epilepsy may gain control over their seizures and enjoy significantly improved quality of life.

Diagnosis, Computer-Assisted↗

Gaussian processes for machine learning.

Gaussian processes (GPs) are natural generalisations of multivariate Gaussian random variables to infinite (countably or continuous) index sets. GPs have been applied in a large number of fields to a diverse range of ends, and very many deep theoretical analyses of various properties are available. This paper gives an introduction to Gaussian processes on a fairly elementary level with special emphasis on characteristics relevant in machine learning. It draws explicit connections to branches such as spline smoothing models and support vector machines in which similar ideas have been investigated. Gaussian process models are routinely used to solve hard machine learning problems. They are attractive because of their flexible non-parametric nature and computational simplicity. Treated within a Bayesian framework, very powerful statistical methods can be implemented which offer valid estimates of uncertainties in our predictions and generic model selection procedures cast as nonlinear optimization problems. Their main drawback of heavy computational scaling has recently been alleviated by the introduction of generic sparse approximations.13,78,31 The mathematical literature on GPs is large and often uses deep concepts which are not required to fully understand most machine learning applications. In this tutorial paper, we aim to present characteristics of GPs relevant to machine learning and to show up precise connections to other "kernel machines" popular in the community. Our focus is on a simple presentation, but references to more detailed sources are provided.

Algorithms↗

The effect of encoding strategy on the neural correlates of memory for faces.

Encoding and recognition of unfamiliar faces in young adults were examined using positron emission tomography to determine whether different encoding strategies would lead to encoding/retrieval differences in brain activity. Three types of encoding were compared: a 'deep' task (judging pleasantness/unpleasantness), a 'shallow' task (judging right/left orientation), and an intentional learning task in which subjects were instructed to learn the faces for a subsequent memory test but were not provided with a specific strategy. Memory for all faces was tested with an old/new recognition test. A modest behavioral effect was obtained, with deeply-encoded faces being recognized more accurately than shallowly-encoded or intentionally-learned faces. Regardless of encoding strategy, encoding activated a primarily ventral system including bilateral temporal and fusiform regions and left prefrontal cortices, whereas recognition activated a primarily dorsal set of regions including right prefrontal and parietal areas. Within encoding, the type of strategy produced different brain activity patterns, with deep encoding being characterized by left amygdala and left anterior cingulate activation. There was no effect of encoding strategy on brain activity during the recognition conditions. Posterior fusiform gyrus activation was related to better recognition accuracy in those conditions encouraging perceptual strategies, whereas activity in left frontal and temporal areas correlated with better performance during the 'deep' condition. Results highlight three important aspects of face memory: (1) the effect of encoding strategy was seen only at encoding and not at recognition; (2) left inferior prefrontal cortex was engaged during encoding of faces regardless of strategy; and (3) differential activity in fusiform gyrus was found, suggesting that activity in this area is not only a result of automatic face processing but is modulated by controlled processes.

Adult↗

Learning- and cerebellum-dependent neuronal activity in the lateral pontine nucleus.

The effects of inactivation of cerebellar deep nuclei and the lateral pontine nucleus on classical eyeblink conditioning with tone or lateral reticular nucleus (LRN) stimulation as conditioned stimuli (CSs) were examined. Inactivation of cerebellar deep nuclei abolished eyeblink conditioned responses (CRs) when the CS was either a tone or LRN stimulation. Inactivation of the lateral pontine nucleus prevented only the acquisition and retention of tone-evoked eyeblink CRs. Multiple-unit recording demonstrated that when LRN stimulation was used as the CS, inactivation of the interpositus nucleus abolished learning-related neuronal activity in the lateral pontine nucleus, whereas inactivation of pontine nucleus had little effect on similar activity in the interpositus nucleus. Thus, the learning-induced neuronal activity in the lateral pontine nucleus was most likely driven by the cerebellar interpositus nucleus.

Acoustic Stimulation↗

The adult form of Niemann-Pick disease type C.

Niemann-Pick disease type C (NPC) is a fatal neurovisceral lipid storage disease of autosomal inheritance resulting from mutations in either the NPC1 (95% of families) or NPC2 gene. The encoded proteins appear to be involved in lysosomal/late endosomal transport of cholesterol, glycolipids and other molecules but their exact function is still unknown. The clinical spectrum of the disease ranges from a neonatal rapidly fatal disorder to an adult-onset chronic neurodegenerative disease. Based upon a comprehensive study of 13 unrelated adult patients diagnosed in France over the past 20 years as well as the analysis of the 55 other cases published since 1969, we have attempted to delineate the major clinical, radiological, biochemical and genotypic characteristics of adult NPC. Overall, mean age at onset (+/-SD) of neuropsychiatric symptoms was 25 +/- 9.7 years. The diagnosis of NPC was established after a mean delay of 6.2 +/- 6.4 years and the mean age at death (calculated from 20 cases) was 38 +/- 10.2 years. Major clinical features included cerebellar ataxia (76%), vertical supranuclear ophthalmoplegia (VSO, 75%), dysarthria, (63%), cognitive troubles (61%), movement disorders (58%), splenomegaly (54%), psychiatric disorders (45%) and dysphagia (37%). Less frequent signs were epilepsy and cataplexy. During the course of the disease, clinical features could be subdivided into (i) visceral signs (hepatomegaly or splenomegaly), (ii) cortical signs (psychiatric cognitive disorders and epilepsy); and (iii) deep brain signs (VSO, ataxia, movement disorders, dysarthria, dysphagia, cataplexy) which exhibited different evolution patterns. Asymptomatic and non-evolutive visceral signs were often noticed since early childhood (38.5% of our patients), followed by mild cortical signs in childhood (learning difficulties) and early adulthood (62% of cases among which 38% were psychiatric disorders). Deep brain signs were observed in 96% of patients and were usually responsible for death. In general, there was a good correlation between clinical signs and the localization of brain atrophy on MRI. The 'variant' biochemical phenotype characterized by mild abnormalities of the cellular trafficking of endocytosed cholesterol was over-represented in the adult form of NPC and seemed associated with less frequent splenomegaly in childhood and lesser psychiatric signs. Involvement of the NPC1 gene was shown in 33 families and of the NPC2 gene in one. Improving the knowledge of the disease among psychiatrists and neurologists appears essential since emerging treatments should be more efficient at the visceral or cognitive/psychiatric stages of the disease, before the occurrence of widespread deep brain neurological lesions.

Adolescent↗

Deep-feeling development gives autistics abstractions: when a young person has no abstractions, his or her thoughts or behaviors frequently seem autistic.

The heart of autism is existence by oneself. It is being, talking and acting by oneself. Talking by oneself is not talking to oneself but talking at others. Its purpose is not exchanging or hearing words. Its purpose is sending words to another person. If being completely by themselves is autistics' experience of their existence, then they may have no need for language. And there is no language development in about half of all autistics. For autistics who do have language, if they are mostly sending out words and are only sometimes exchanging or hearing words, then another person's language has little or no effect on them. Without language from outside persons as a guide, autistics' language becomes strange and free from the normal body motions (gestures) that come with language. So strange language and uncommon body motions with that language are two of autism's chief signs. Autistics are unnerved by change. So they keep their behaviors in a narrow range and do them over and over with no connection to other persons' purposes. A narrow range of behaviors done over and over for no seeming purpose is another chief sign of autism. Because young boys and girls get to being, talking and acting by themselves when they come down with autism, they no longer seem to have any idea of what is going on between themselves and other persons. So when boys and girls get autism, they frequently do or say strange and surprising things with other persons. The knowledge of what to do and say with other persons comes as abstractions. This paper's one hypothesis is that autistic persons have no abstractions because the development of their deep feelings has not gone far enough to let abstractions come into existence. By acting or talking without the support of abstractions, autistic persons have a hard time with language, learning, living and loving in relation to other persons or to society. Autism comes from stopping the development of a baby's deep feelings within the first six months after birth. The development of deep feelings may be started again by a special operation named deep-feeling contact. (Body-to-body touching is never necessary for making deep-feeling contact.) As the development of his or her deep feelings goes forward, the autistic person's abstractions come into existence. Then language, learning, living and loving become much simpler for him or her.

Autistic Disorder↗

Midbrain reticular stimulation produces patterns of metabolic activation and suppression in the cerebellum and vestibular nuclei: a 2-deoxyglucose study.

Autoradiographic 2-deoxyglucose (2-DG) procedures were used to map the activity in the cerebellum and vestibular nuclei during electrical stimulation of the midbrain reticular formation (MRF) in unrestrained rats. The major finding was a large increase in 2-DG uptake observed in the flocculus of MRF-stimulated rats. The peak of labeling in the flocculus was greater than any other peak of labeling measured in the cerebellum of MRF-stimulated or control rats. Structures showing significant decreases in 2-DG uptake included the 3 deep cerebellar nuclei and the 3 vestibular nuclei. The most pronounced suppressive effects of MRF stimulation were on the medial and lateral vestibular nuclei. The changes in metabolic activity revealed by 2-DG provide a first anatomical demonstration of: the activating effects of MRF stimulation on the flocculus; and the suppressive effects of MRF stimulation on deep cerebellar and vestibular nuclei. The observed patterns of metabolic activation and suppression were correlated with the known electrophysiological properties of the structures affected by MRF stimulation. The findings are consistent with specific effects of MRF stimulation on floccular-vestibular-visual interactions that may be disruptive to learning functions such as adaptability of the vestibulo-ocular reflex. The effects of MRF stimulation on the deep cerebellar nuclei are also consistent with a potential disruption of somatomotor learning-related activities in these nuclei. The results support the existence of MRF mechanisms for the modulation of integrative sensory-motor functions in the cerebellum.

Animals↗

Performance of children with good and poor articulation on tasks of tongue placement.

This study determined whether children could learn to replicate four positions of lingual-palatal contact with and without topical anesthesia that eliminated touch-pressure sensations. First-grade boys, nine with good articulation skills and nine with poor articulation skills, were used as subjects. Results suggest that individuals are able to learn nonspeech tasks of tongue positioning by relying on muscle spindles or deep receptors within the tongue, or both, or by relying on lingual touch-pressure or other surface receptors within the tongue, or, by a combination of deep and surface receptors of the tongue. Further, tongue positioning need not be dependent on touch-pressure or superficial tactile mechanisms. Children with relatively severe articulation problems performed more poorly on the tasks of precise tongue placement than children with good articulation skills. And finally, children with relatively severe articulation problems may be able to improve their initially poor performance on tongue placement tasks with specific training on those tasks, implying that this group did receive the intraoral sensory feedback necessary to learn the task, but that more experience was needed for the learning to occur.

Child↗

From Binswanger's disease to leuokoaraiosis: what we have learned about subcortical vascular dementia.

The literature regarding subcortical vascular dementia associated with periventricular and deep white matter alterations is reviewed. Information pertaining to neuropathological, neuropsychological, and neuroradiological studies is emphasized. Based on this review and prior neuropsychological studies associating subcortical vascular pathology with greater deficits on tests of executive dysfunction and with relatively better performance on tests of delayed recognition memory, we conclude that vascular dementia associated with periventricular and deep white matter alterations can and should be regarded as a subcortical dementing illness. Also, we support schemes suggested by Erkinjuntti et al. (2000) and Cosentino et al. (this issue) that attempt to integrate neuropsychological and neuroradiological data into a diagnostic paradigm that describes, as well as diagnoses, dementing disorders. We discuss questions and issues about vascular dementia that deserve further consideration and study.

Cerebral Infarction↗

Nitric oxide synthase (NOS) in the brain of the cephalopod Sepia officinalis.

Nitric oxide synthase-like protein (NOS) is shown to be present in specific regions of the central nervous system (CNS) of the cephalopod mollusc Sepia officinalis (cuttlefish). NOS activity, which is Ca(2+)/calmodulin-dependent, was determined by measuring the conversion of L-[(14)C]arginine in L-[(14)C]citrulline. The partially purified NOS from brain and optic lobes exhibited on SDS-PAGE a band at 150 kDa that was immunolabelled by antibodies raised against the synthetic peptide corresponding to the amino acids 1,414-1,429 of the C-terminus of rat nNOS. This same antibody was then used for immunohistochemical staining of serial sections of the cuttlefish CNS to reveal localized specific staining of cell bodies and fibers in several lobes of the brain. Staining was found in many lower motor centers, including cells and fibers of the inferior and superior buccal lobes (feeding centers); in some higher motor centers (anterior basal and peduncle lobes); in learning centers (vertical, subvertical, and superior frontal lobes); and in the visual system [retina and deep retina (optic lobe)]. Immunopositivity was also found in the olfactory lobe and organ and in the sucker epithelium. These findings suggest that nitric oxide (NO) may be involved as a signaling molecule in feeding, motor, learning, visual, and olfactory systems in the cuttlefish brain. The presence of NOS in the cephalopod "cerebellum" and learning centers is discussed in the context of the vertebrate CNS.

Animals↗