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PubMed2006

Enrichment analysis in high-throughput genomics - accounting for dependency in the NULL.

Translating the overwhelming amount of data generated in high-throughput genomics experiments into biologically meaningful evidence, which may for example point to a series of biomarkers or hint at a relevant pathway, is a matter of great interest in bioinformatics these days. Genes showing similar experimental profiles, it is hypothesized, share biological mechanisms that if understood could provide clues to the molecular processes leading to pathological events. It is the topic of further study to learn if or how a priori information about the known genes may serve to explain coexpression. One popular method of knowledge discovery in high-throughput genomics experiments, enrichment analysis (EA), seeks to infer if an interesting collection of genes is 'enriched' for a Consortium particular set of a priori Gene Ontology Consortium (GO) classes. For the purposes of statistical testing, the conventional methods offered in EA software implicitly assume independence between the GO classes. Genes may be annotated for more than one biological classification, and therefore the resulting test statistics of enrichment between GO classes can be highly dependent if the overlapping gene sets are relatively large. There is a need to formally determine if conventional EA results are robust to the independence assumption. We derive the exact null distribution for testing enrichment of GO classes by relaxing the independence assumption using well-known statistical theory. In applications with publicly available data sets, our test results are similar to the conventional approach which assumes independence. We argue that the independence assumption is not detrimental.

Data Interpretation, Statistical↗
PubMed2006

EEG evidence of gender differences in a motor related CNV study.

In the present study gender differences related to the contingent negative variation (CNV) were investigated. A series of two acoustic stimuli was presented to participants across a wide age range. The first stimulus was consistent throughout the experiment whereas the second one was either a high frequency or a low frequency tone. One of them had to be answered by a button press (go condition) the other did not require any response (nogo condition). Between the first and the second tone there was a time period of two seconds in which the CNV appeared as a slow negative potential shift. Within this episode data were analysed with respect to gender differences. Statistical analysis revealed topographical differences between men and women in go conditions for both left and right index finger movements. Differences were found over frontal regions where women showed higher brain activity than men and over temporo-parietal regions where men produced higher brain activity than women. In order to explain the fact that only in "go" conditions significant gender differences occurred we introduce the phenomenon of implicit learning. Due to implicit learning assumed predictions related to S2 might have occurred from time to time. This is so, because a 50% chance for one of two different stimuli to occur leads to reasonable assumed predictions after two or more stimuli of a kind occurring in a series. The present data now provide evidence that if such assumed prediction or expectancy is directed towards an upcoming demand to act then brain activity is subject to gender differences. Further studies providing controlled sequences of "go" conditions versus "nogo" conditions have to be done to prove this idea true.

Acoustic Stimulation↗
PubMed2003

Selective memory and memory deficits in depressed inpatients.

We investigated memory impairment and mood-congruent memory bias in depression, using an explicit memory test and an implicit one. Thirty-six severely depressed inpatients that fulfilled DSM-IV criteria for major depressive disorder and 36 healthy controls matched for sex, age, and educational level participated in the study. Explicit memory was assessed with a free recall task and implicit memory with an anagram solution task. Results showed that depressed and controls differed in explicit memory performance, depending on the amount of cognitive distraction between incidental learning and testing. Implicit memory was not affected. In addition, severely depressed patients showed a mood-congruent memory bias in implicit memory but not in explicit memory. The complex pattern of results is discussed with regard to relevant theories of depression.

Adult↗
PubMed2002

A Monte Carlo EM approach for partially observable diffusion processes: theory and applications to neural networks.

We present a Monte Carlo approach for training partially observable diffusion processes. We apply the approach to diffusion networks, a stochastic version of continuous recurrent neural networks. The approach is aimed at learning probability distributions of continuous paths, not just expected values. Interestingly, the relevant activation statistics used by the learning rule presented here are inner products in the Hilbert space of square integrable functions. These inner products can be computed using Hebbian operations and do not require backpropagation of error signals. Moreover, standard kernel methods could potentially be applied to compute such inner products. We propose that the main reason that recurrent neural networks have not worked well in engineering applications (e.g., speech recognition) is that they implicitly rely on a very simplistic likelihood model. The diffusion network approach proposed here is much richer and may open new avenues for applications of recurrent neural networks. We present some analysis and simulations to support this view. Very encouraging results were obtained on a visual speech recognition task in which neural networks outperformed hidden Markov models.

Algorithms↗
PubMed1993

A measure of consciousness and memory during isoflurane administration: the coherent frequency.

The coherent frequency (CF) of the auditory evoked response (AER) is derived using auditory clicks presented at frequencies in the range 5-47 Hz. CF and psychological performance were measured while seven subjects breathed isoflurane in doses increasing from 0% to 0.2%, 0.4% and 0.8% end-tidal concentration and then decreasing to 0%. With increasing doses of isoflurane, CF decreased and there was a decrease in within-list recognition (WLR) and category recognition (CR) scores. There was a correlation between changes in CF and WLR (P < 0.05) and between CF and category recognition (CR) (P < 0.05). A painful stimulus given in conjunction with 0.4% isoflurane caused an increase in CF, WLR and CR in some subjects. This did not reach statistical significance for the group as a whole, apart from the short word interval scores in the WLR which indicated an increase in attention (P < 0.01). Subjects did not respond with 0.8% isoflurane, either before or after painful stimulation. Reduction of end-tidal isoflurane from 0.8% to 0% caused an increase in the CF and improved performance on the psychological tests. A category generation task on recovery showed no evidence of implicit learning of words presented in conjunction with 0.8% isoflurane.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed2005

Statistical shape analysis: clustering, learning, and testing.

Using a differential-geometric treatment of planar shapes, we present tools for: 1) hierarchical clustering of imaged objects according to the shapes of their boundaries, 2) learning of probability models for clusters of shapes, and 3) testing of newly observed shapes under competing probability models. Clustering at any level of hierarchy is performed using a mimimum variance type criterion criterion and a Markov process. Statistical means of clusters provide shapes to be clustered at the next higher level, thus building a hierarchy of shapes. Using finite-dimensional approximations of spaces tangent to the shape space at sample means, we (implicitly) impose probability models on the shape space, and results are illustrated via random sampling and classification (hypothesis testing). Together, hierarchical clustering and hypothesis testing provide an efficient framework for shape retrieval. Examples are presented using shapes and images from ETH, Surrey, and AMCOM databases.

Algorithms↗
PubMed1992

International infant mortality rankings: a look behind the numbers.

The very unfavorable infant mortality ranking of the United States in international comparisons is often used to question the quality of health care there. Infant mortality rates, however, implicitly capture a complicated story, measuring much more than differences in health care across countries. This article examines reasons behind international infant mortality rate rankings, including variations in the measurement of vital events, and differences in risk factors across countries. Its goal is to offer a broader context for more informed debate on the meaning of international infant mortality statistics. These statistics offer opportunities to identify strategies for improving the U.S. health care system and learn from other countries that have been more successful.

Adolescent↗
PubMed2005

An attitudinal study of responses to a range of dermatological conditions using the implicit association test.

The Implicit Association Test (IAT) was used to explore implicit attitudes to dermatological conditions. The stimuli employed were photographs representing skin conditions and clear skin. Explicit attitudes were measured using rating scales and questions concerning participants' experience of dermatitis. Participants (N=64) completed the IAT, explicit measures and demographics. The results showed a statistically significant implicit preference for people with clear skin and suggested that people who knew someone with a skin condition may exhibit stereotype inhibition. This concurs with earlier research into disfigurement, and in accord with previous IAT research, correlations between implicit and explicit measures were not significant.

Adolescent↗
PubMed2003

Event-related brain potentials in memory: correlates of episodic, semantic and implicit memory.

OBJECTIVE: To study cognitive evoked potentials, recorded from scalp EEG and foramen ovale electrodes, during activation of explicit and implicit memory. The subgroups of explicit memory, episodic and semantic memory, are looked at separately. METHODS: A word-learning task was used, which has been shown to activate hippocampus in H(2)(15)O positron emission tomography studies. Subjects had to study and remember word pairs using different learning strategies: (i) associative word learning (AWL), which activates the episodic memory, (ii) deep single word encoding (DSWE), which activates the semantic memory, and (iii) shallow single word encoding (SSWE), which activates the implicit memory and serves as a baseline. The test included the 'remember/know' paradigm as a behavioural learning control. During the task condition, a 10-20 scalp EEG with additional electrodes in both temporal lobes regions was recorded from 11 healthy volunteers. In one patient with mesiotemporal lobe epilepsy, the EEG was recorded from bilateral foramen ovale electrodes directly from mesial temporal lobe structures. Event-related potentials (ERPs) were calculated off-line and visual and statistical analyses were made. RESULTS: Associative learning strategy produced the best memory performance and the best noetic awareness experience, whereas shallow single word encoding produced the worst performance and the smallest noetic awareness. Deep single word encoding performance was in between. ERPs differed according to the test condition, during both encoding and retrieval, from both the scalp EEG and the foramen ovale electrode recordings. Encoding showed significant differences between the shallow single word encoding (SSWE), which is mainly a function of graphical characteristics, and the other two strategies, deep single word (DSWE) and associative learning (AWL), in which there is a semantic processing of the meaning. ERPs generated by these two categories, which are both functions of explicit memory, differed as well, indicating the presence or the absence of associative binding. Retrieval showed a significant test effect between the word pairs learned by association (AWL) and the ones learned by encoding the words in isolation of each other (DSWE and SSWE). The comparison of the ERPs generated by autonoetic awareness ('remember') and noetic awareness ('know') exhibited a significant test effect as well. CONCLUSIONS: The results of behavioural data, in particular that of the 'remember/know' procedure, are evidence that the task paradigm was efficient in activating different kinds of memory. Associative word learning generated a high degree of autonoetic awareness, which is a result of the episodic memory, whereas both kinds of single word learning generated less. AWL, DSWE and SSWE resulted in different electrophysiological correlates, both for encoding as well as retrieval, indicating that different brain structures were activated in different temporal sequence.

Adult↗
PubMed2005

The implicit sequence learning deficit in patients with Parkinson's disease: a matter of impaired sequence integration?

Despite the wealth of research investigating the serial reaction time (SRT) learning abilities of people with Parkinson's disease (PD), the role of the basal ganglia in implicit sequence learning remains largely unclear. The present research sought to examine the ability of people with PD to implicitly learn simultaneously operating sequences and integrate patterned information from each sequence dimension. Using a version of the SRT which reduced motor demands, the present experiment investigated the implicit learning of a spatial sequence, a stimulus-response sequence, and an integrated spatial/stimulus-response sequence, all of which are usually confounded in the standard SRT task. Whereas both PD and control groups demonstrated robust learning for the individual spatial and response sequences, only control participants evidenced learning for the integrated sequence. Further, unlike implicit learning for the spatial and object sequences, impaired integrated sequence acquisition was specifically related to the severity of patients' PD symptomatology. The implicit learning deficits of PD patients are discussed with regard to the role played by the basal ganglia in integrative sequence learning in the SRT.

Aged↗
PubMed2004

Robust sparse hyperplane classifiers: application to uncertain molecular profiling data.

Molecular profiling studies can generate abundance measurements for thousands of transcripts, proteins, metabolites, or other species in, for example, normal and tumor tissue samples. Treating such measurements as features and the samples as labeled data points, sparse hyperplanes provide a statistical methodology for classifying data points into one of two categories (classification and prediction) and defining a small subset of discriminatory features (relevant feature identification). However, this and other extant classification methods address only implicitly the issue of observed data being a combination of underlying signals and noise. Recently, robust optimization has emerged as a powerful framework for handling uncertain data explicitly. Here, ideas from this field are exploited to develop robust sparse hyperplanes, i.e., classification and relevant feature identification algorithms that are resilient to variation in the data. Specifically, each data point is associated with an explicit data uncertainty model in the form of an ellipsoid parameterized by a center and covariance matrix. The task of learning a robust sparse hyperplane from such data is formulated as a second order cone program (SOCP). Gaussian and distribution-free data uncertainty models are shown to yield SOCPs that are equivalent to the SCOP based on ellipsoidal uncertainty. The real-world utility of robust sparse hyperplanes is demonstrated via retrospective analysis of breast cancer related transcript profiles. Data-dependent heuristics are used to compute the parameters of each ellipsoidal data uncertainty model. The generalization performance of a specific implementation, designated "robust LIKNON," is better than its nominal counterpart. Finally, the strengths and limitations of robust sparse hyperplanes are discussed.

Breast Neoplasms↗
PubMed2001

Prefrontal lesions impair the implicit and explicit learning of sequences on visuomotor tasks.

OBJECTIVE: (1) To verify whether the prefrontal cortex (PFC) is specifically involved in visuomotor sequence learning as opposed to other forms of motor learning and (2) to establish the role of executive functions in visuomotor sequence learning. BACKGROUND: Visuomotor skill learning depends on the integrity of the premotor and parietal cortex; the prefrontal cortex, however, is essential when the learning of a sequence is required. METHODS: We studied 25 patients with PFC lesions and 86 controls matched for age and educational level. Participants performed: (1) a Pursuit Tracking Task (PTT), composed of a random tracking task (perceptual learning) and a pattern tracking task (explicit motor sequence learning with learning indicated by the decrease in mean root square error across trial blocks), (2) a 12-item sequence version of a serial reaction time task (SRTT) with specific implicit motor sequence learning indicated by the rebound increase in response time when comparing the last sequence block with the next random block, and (3) a neuropsychological battery that assessed executive functions. RESULTS: PFC patients were impaired in sequence learning on the pattern tracking task of the PTT and on the SRTT as compared to controls, but performed normally on the PTT random tracking task. Learning on the PTT did not correlate with learning on the SRTT. PTT performance correlated with planning functions while SRTT performance correlated with working memory capacity. CONCLUSIONS: The PFC is specifically involved in explicit and implicit motor sequence learning. Different PFC regions may be selectively involved in such learning depending on the cognitive demands of the sequential task.

Adult↗
PubMed2003

Implicit learning in memory rehabilitation: a meta-analysis on errorless learning and vanishing cues methods.

The objective of this study was to present a quantitative review on the treatment effects of memory rehabilitation techniques based on intact implicit learning capacity in amnesic patients, that is, errorless learning and the method of vanishing cues. English-language journal articles focusing on these rehabilitation techniques were examined using MedLine (1966-2002) or PsychInfo (1887-2002), as well as additional papers listed in the references of these articles. Studies had to meet the following inclusion criteria: (1) original data were reported, (2) memory rehabilitation was studied in memory-impaired patients, (3) a control intervention was included, (4) exact scores were listed for both intervention conditions, or the exact statistics were presented. Studies were classified on the basis of the to-be-learned material and the method of intervention (errorless learning, vanishing cues, control intervention), patient characteristics were determined, and the tasks that were used were taken into account. Effect sizes and variances were computed for each individual study compared to control treatment using within-group statistics. A "large" and statistically significant ES was found for errorless learning treatment, but no significant ES was demonstrated for the vanishing cues method. The results of the present study show that the errorless learning technique is effective in amnesic patients. The effects on the vanishing cues method are only small (and nonsignificant).

Adult↗
PubMed2004

Functional magnetic resonance imaging evidence for a lack of striatal dysfunction during implicit sequence learning in individuals with animal phobia.

OBJECTIVE: This study investigated the neural substrates of implicit sequence learning in subjects with and without small animal phobia, in a follow-up to analogous studies of obsessive-compulsive disorder (OCD). METHOD: Ten subjects with specific phobia and 10 healthy comparison subjects were studied by using a serial reaction time task paradigm and functional magnetic resonance imaging. RESULTS: A main effect of condition (implicit sequence learning versus random sequence) was observed across diagnostic groups in the right striatum, as well as in other regions. In the striatum, the a priori region of interest, there were no significant effects of diagnosis or the interaction of diagnosis and condition. CONCLUSIONS: Brain activation in the striatum of subjects with specific phobia does not significantly differ from that of normal comparison subjects during implicit sequence learning. This suggests different pathophysiological mechanisms for specific phobia in contrast to OCD, in which deficient striatal recruitment has been reproducibly found with this paradigm. This approach offers promise for demonstrating diagnostic specificity across different neuropsychiatric disorders based on the presence or absence of deficient striatal activation.

Adult↗
PubMed2005

Dyslexics are impaired on implicit higher-order sequence learning, but not on implicit spatial context learning.

Developmental dyslexia is characterized by poor reading ability and impairments on a range of tasks including phonological processing and processing of sensory information. Some recent studies have found deficits in implicit sequence learning using the serial reaction time task, but others have not. Other skills, such as global visuo-spatial processing may even be enhanced in dyslexics, although deficits have also been noted. The present study compared dyslexic and non-dyslexic college students on two implicit learning tasks, an alternating serial response time task in which sequential dependencies exist across non-adjacent elements and a spatial context learning task in which the global configuration of a display cues the location of a search target. Previous evidence indicates that these implicit learning tasks are based on different underlying brain systems, fronto-striatal-cerebellar circuits for sequence learning and medial temporal lobe for spatial context learning. Results revealed a double dissociation: dyslexics showed impaired sequence learning, but superior spatial context learning. Consistent with this group difference, there was a significant positive correlation between reading ability (single real and non-word reading) and sequence learning, but a significant negative correlation between these measures and spatial context learning. Tests of explicit knowledge confirmed that learning was implicit for both groups on both tasks. These findings indicate that dyslexic college students are impaired on some kinds of implicit learning, but not on others. The specific nature of their learning deficit is consistent with reports of physiological and anatomical differences for individuals with dyslexia in frontal and cerebellar structures.

Adolescent↗
PubMedDate not supplied

BYY harmony learning, structural RPCL, and topological self-organizing on mixture models.

The Bayesian Ying-Yang (BYY) harmony learning acts as a general statistical learning framework, featured by not only new regularization techniques for parameter learning but also a new mechanism that implements model selection either automatically during parameter learning or via a new class of model selection criteria used after parameter learning. In this paper, further advances on BYY harmony learning by considering modular inner representations are presented in three parts. One consists of results on unsupervisedmixture models, ranging from Gaussian mixture based Mean Square Error (MSE) clustering, elliptic clustering, subspace clustering to NonGaussian mixture based clustering not only with each cluster represented via either Bernoulli-Gaussian mixtures or independent real factor models, but also with independent component analysis implicitly made on each cluster. The second consists of results on supervised mixture-of-experts (ME) models, including Gaussian ME, Radial Basis Function nets, and Kernel regressions. The third consists of two strategies for extending the above structural mixtures into self-organized topological maps. All these advances are introduced with details on three issues, namely, (a) adaptive learning algorithms, especially elliptic, subspace, and structural rival penalized competitive learning algorithms, with model selection made automatically during learning; (b) model selection criteria for being used after parameter learning, and (c) how these learning algorithms and criteria are obtained from typical special cases of BYY harmony learning.

Bayes Theorem↗
PubMed2000

Commentary on the multimodal treatment study of children with ADHD.

The multimodal treatment study of attention deficit hyperactivity disorder (MTA Study) constitutes a landmark in the history of treatment research in child psychopathology, being the largest single study of its kind ever undertaken. Important findings have emerged from this project, as the papers in the present volume will attest. This commentary focuses on several concerns about the assumptions that appear to have guided the design of the MTA study, particularly its psychosocial treatment component, as well as the manner in which treatment results have been presented to date. In particular, no explicit theory of ADHD appears to have guided the construction of the treatment components, relying instead on implicit theories associated with those treatments, such as the notion that the symptoms of ADHD arise through faulty learning and defective contingencies of reinforcement. Future articles from this study will need to address these and other concerns if the results of the study are to be properly interpreted and the scientific and clinical yield is to be maximized.

Attention Deficit Disorder with Hyperactivity↗
PubMed1987

Mechanical efficiency and metabolic cost as measures of learning a novel gross motor task.

"Efficiency, " or economy of movement with respect to energy expended in achieving the goal of the task, is implicit in many definitions of skilled performance. This study examined changes in mechanical efficiency and transport efficiency on a novel gross motor skill. The subjects were 5 physically fit adult males who were asked to perform 20 3-min trials walking on hands and feet (crawling) on a motor-driven treadmill at constant speed (0.76 m/s). Transport efficiency, the metabolic cost of transporting the body mass a given distance at constant speed, improved significantly over practice trials. Mechanical efficiency, derived from the mechanical power output of individual body segments, showed an overall improvement of 13.7% by the last day of practice. Even though this improvement was not statistically significant it appears to be greater than that expected due to physiological training effects. The efficiency measures correlated significantly with changes in limb kinematics. It was concluded that with practice subjects tailored their movement pattern to produce energy efficient adaptations to task constraints. These findings provide empirical support for theoretical perspectives that have emphasized biological principles in the organization of motor coordination and control.

Journal Article↗