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A free energy principle for the brain.

By formulating Helmholtz's ideas about perception, in terms of modern-day theories, one arrives at a model of perceptual inference and learning that can explain a remarkable range of neurobiological facts: using constructs from statistical physics, the problems of inferring the causes of sensory input and learning the causal structure of their generation can be resolved using exactly the same principles. Furthermore, inference and learning can proceed in a biologically plausible fashion. The ensuing scheme rests on Empirical Bayes and hierarchical models of how sensory input is caused. The use of hierarchical models enables the brain to construct prior expectations in a dynamic and context-sensitive fashion. This scheme provides a principled way to understand many aspects of cortical organisation and responses. In this paper, we show these perceptual processes are just one aspect of emergent behaviours of systems that conform to a free energy principle. The free energy considered here measures the difference between the probability distribution of environmental quantities that act on the system and an arbitrary distribution encoded by its configuration. The system can minimise free energy by changing its configuration to affect the way it samples the environment or change the distribution it encodes. These changes correspond to action and perception respectively and lead to an adaptive exchange with the environment that is characteristic of biological systems. This treatment assumes that the system's state and structure encode an implicit and probabilistic model of the environment. We will look at the models entailed by the brain and how minimisation of its free energy can explain its dynamics and structure.

Afferent Pathways↗

Not the same everywhere. Patient-centered learning environments at nine medical schools.

BACKGROUND: Learning environments overtly or implicitly address patient-centered values and have been the focus of research for more than 40 years, often in studies about the "hidden curriculum." However, many of these studies occurred at single medical schools and used time-intensive ethnographic methods. This field of inquiry lacks survey methods and information about how learning environments differ across medical schools. OBJECTIVE: To examine patient-centered characteristics of learning environments at 9 U.S. medical schools. DESIGN: Cross-sectional internet-based survey. PARTICIPANTS: Eight-hundred and twenty-three third- and fourth-year medical students in the classes of 2002 and 2003. MEASUREMENTS: We measured the patient-centeredness of learning environments with the Communication, Curriculum, and Culture (C3) Instrument, a 29-item validated measure that characterizes the degree to which a medical school's environment fosters patient-centered care. The C3 Instrument contains 3 content areas (role modeling, students' experiences, and support for students' patient-centered behaviors), and is designed to measure these areas independent of respondents' attitudes about patient-centered care. We also collected demographic and attitudinal information from respondents. RESULTS: The variability of C3 scores across schools in each of the 3 content areas of the instrument was striking and statistically significant (P values ranged from .001 to .004). In addition, the patterns of scores on the 3 content areas differed from school to school. CONCLUSIONS: The 9 schools demonstrated unique and different learning environments both in terms of magnitude and patterns of characteristics. Further multiinstitutional study of hidden curricula is needed to further establish the degree of variability that exists, and to assist educators in making informed choices about how to intervene at their own schools.

Adult↗

A boosting approach to flexible semiparametric mixed models.

In linear mixed models the influence of covariates is restricted to a strictly parametric form. With the rise of semi- and non-parametric regression also the mixed model has been expanded to allow for additive predictors. The common approach uses the representation of additive models as mixed models. An alternative approach that is proposed in the present paper is likelihood based boosting. Boosting originates in the machine learning community where it has been proposed as a technique to improve classification procedures by combining estimates with reweighted observations. Likelihood based boosting is a general method which may be seen as an extension of L2 boost. In additive mixed models the advantage of boosting techniques in the form of componentwise boosting is that it is suitable for high dimensional settings where many explanatory variables are present. It allows to fit additive models for many covariates with implicit selection of relevant variables and automatic selection of smoothing parameters. Moreover, boosting techniques may be used to incorporate the subject-specific variation of smooth influence functions by specifying 'random slopes' on smooth effects. This results in flexible semiparametric mixed models which are appropriate in cases where a simple random intercept is unable to capture the variation of effects across subjects.

Cohort Studies↗

Exploring mental status in Friedreich's ataxia: a combined neuropsychological, behavioral and neuroimaging study.

Despite much evidence of cognitive and affective disorders in Friedreich's ataxia (FRDA), the nature of mental status in FRDA has received little systematic attention. It has been proposed that the cerebellum may interfere indirectly with cognition through the cerebello-cortical loops, whereas the role of pathological changes in different areas of the central nervous system is still undetermined. In the present study, 13 patients with molecularly determined FRDA and a group of matched controls were evaluated by a comprehensive battery of neuropsychological tests and the Minnesota Multiphasic Personality Inventory. A repetitive task of simple visual-reaction times was used to investigate implicit learning in all subjects. Pathological changes in cortical areas were explored comparing cerebral activations of patients and controls during finger movements (functional MRI). The intelligence profile of FRDA patients is characterized by concrete thinking, poor capacity in concept formation and visuospatial reasoning. FRDA patients show reduced speed of information processing. The learning effect seen in controls was notably absent in patients with FRDA. The patients' personality is characterized by some pathological aspects and reduced defensiveness. Patterns of cortical activation during finger movements are heterogeneous in patients compared to controls. Cognitive impairment, mood disorders and motor deficits in FRDA patients may be the result of the cumulative damage caused by frataxin deficiency not only in the cerebellum and spinal cord but also in other brain areas.

Adolescent↗

Speech errors reflect newly learned phonotactic constraints.

Speech errors reveal the speaker's implicit knowledge of phonotactic constraints, both languagewide constraints (e.g., /K/ cannot be a syllable onset when one is speaking English) and experimentally induced constraints (e.g., /k/ cannot be an onset during the experiment). Four experiments investigated the acquisition of novel 2nd-order constraints, in which the allowable position of a consonant depends on some other property of the syllable (e.g., /k/ can only be an onset if the vowel is /I/). Participants recited strings of syllables that exhibited the novel constraints throughout a 4-day experiment. Their errors reflected the newly learned constraints but not until the 2nd day of training. This contrasts with previous research showing that errors become sensitive to 1st-order constraints almost immediately. A model that learns to assign phonemes to syllable positions is presented. It attributes the relative slowness of the acquisition of 2nd-order constraints to the self-interfering property of these constraints.

Humans↗

Reliability of individual functional MRI brain mapping of language.

The use of individual brain mapping for a single case study implicitly assumes that the pattern of activation obtained in a single session represents the subject's functional neuroanatomy. It is therefore essential to estimate the potential variability of brain activation in individuals. To this purpose, the authors compared the pattern of activation determined by statistical parametric mapping (SPM 99) in 9 subjects who repeated 3 verbal tasks in 3 separate sessions. In each subject for each task, the authors examined the intersession variability of the volume of activation in a set of regions classically implicated in language processing. Their results show that reproducibility of functional MRI brain mapping for language within subject varies as a function of the activation task and the region of interest for language.

Adult↗

Discussion between reviewers does not improve reliability of peer review of hospital quality.

OBJECTIVES: Peer review is used to make final judgments about quality of care in many quality assurance activities. To overcome the low reliability of peer review, discussion between several reviewers is often recommended to point out overlooked information or allow for reconsideration of opinions and thus improve reliability. The authors assessed the impact of discussion between 2 reviewers on the reliability of peer review. METHODS: A group of 13 board-certified physicians completed a total of 741 structured implicit record reviews of 95 records for patients who experienced severe adverse events related to laboratory abnormalities while in the hospital (hypokalemia, hyperkalemia, renal failure, hyponatremia, and digoxin toxicity). They independently assessed the degree to which each adverse event was caused by medical care and the quality of the care leading up to the adverse event. Working in pairs, they then discussed differences of opinion, clarified factual discrepancies, and rerated the record. The authors compared the reliability of each measure before and after discussion, and between and within pairs of reviewers, using the intraclass correlation coefficient for continuous ratings and the kappa statistic for a dichotomized rating. RESULTS: The assessment of whether the laboratory abnormality was iatrogenic had a reliability of 0.46 before discussion and 0.71 after discussion between paired reviewers, indicating considerably improved agreement between the members of a pair. However, across reviewer pairs, the reviewer reliability was 0.36 before discussion and 0.40 after discussion. Similarly, for the rating of overall quality of care, reliability of physician review went from 0.35 before discussion to 0.58 after discussion as assessed by pair. However, across pairs the reliability increased only from 0.14 to 0.17. Even for prediscussion ratings, reliability was substantially higher between 2 members of a pair than across pairs, suggesting that reviewers who work in pairs learn to be more consistent with each other even before discussion, but this consistency also did not improve overall reliability across pairs. CONCLUSIONS: When 2 physicians discuss a record that they are reviewing, it substantially improves the agreement between those 2 physicians. However, this improvement is illusory, as discussion does not improve the overall reliability as assessed by examining the reliability between physicians who were part of different discussions. This finding may also have implications with regard to how disagreements are resolved on consensus panels, guideline committees, and reviews of literature quality for meta-analyses.

Causality↗

Implicit learning in 3D object recognition: the importance of temporal context.

A novel architecture and set of learning rules for cortical self-organization is proposed. The model is based on the idea that multiple information channels can modulate one another's plasticity. Features learned from bottom-up information sources can thus be influenced by those learned from contextual pathways, and vice versa. A maximum likelihood cost function allows this scheme to be implemented in a biologically feasible, hierarchical neural circuit. In simulations of the model, we first demonstrate the utility of temporal context in modulating plasticity. The model learns a representation that categorizes people's faces according to identity, independent of viewpoint, by taking advantage of the temporal continuity in image sequences. In a second set of simulations, we add plasticity to the contextual stream and explore variations in the architecture. In this case, the model learns a two-tiered representation, starting with a coarse view-based clustering and proceeding to a finer clustering of more specific stimulus features. This model provides a tenable account of how people may perform 3D object recognition in a hierarchical, bottom-up fashion.

Animals↗

Intentional versus unintentional use of contingencies between perceptual events.

In three experiments we studied human ability to use statistical contingencies between visual stimuli (flankers and targets) to improve performance in a letter-digit classification task. We compared the performance of explicitly informed subjects with that of subjects who were told nothing of the contingencies. Simultaneous presentation of flankers and targets (Experiment 1) produced evidence of unintentional contingency use by both informed and uninformed subjects. When stimuli on trial n predicted target stimuli on trial n + 1 (Experiment 2) there was no evidence of unintentional processes, but informed subjects showed strong evidence of using intentional prediction strategies. When flanker onset preceded target stimuli presentation (Experiment 3), evidence of contingency use by both informed and uninformed subjects was found, but the data illustrated qualitative differences in response style (e.g., speed-accuracy tradeoffs) between the two groups. Intentional and unintentional uses of contingencies between perceptual events are qualitatively distinct with respect to the time frame in which they can be applied and the performance patterns they produce. Finally, we argue that the unintentional processes studied here are implicit in nature.

Adult↗

Avoidant personality disorder and implicit schema-congruent information processing bias: a pilot study with a pragmatic inference task.

Cognitive theory of personality disorders hypothesizes that each personality disorder is characterized by typical maladaptive schemes and that these schemas direct the processing of information resulting in schema-congruent biases. With regard to the avoidant personality disorder, these hypotheses were put to an initial test in a pilot study, using a self-report questionnaire to asses DSM-III-R personality pathology, a belief questionnaire to assess avoidant schemas and a pragmatic inference task to assess schema-congruent implicit attributional bias. Participants were students (n = 57) who scored high or low on DSM-III-R avoidant personality pathology. As predicted from cognitive theory, DSM-III-R avoidant personality pathology was associated with avoidant beliefs (t(45.1) = 4.68, p < 0.001) and avoidant beliefs were associated with schema-congruent information processing bias (t(55) = 2.17, p = 0.02, one-tailed test). However, DSM-III-R avoidant personality pathology was not associated with schema-congruent information processing bias (t(55) = 0.17, p = 0.43, one-tailed test). In addition to avoidant beliefs, low self-esteem was also related to the information processing bias. Social phobia and general personality pathology, two other control variables, were not. The findings warrant further study using the pragmatic inference task in a clinical group.

Adolescent↗

Dissociation between intentional and incidental sequence learning in Huntington's disease.

The ability to acquire and act upon serial order information is fundamental to almost all forms of adaptive behaviour. There is growing evidence that such knowledge may be acquired through a number of different means, each perhaps with its own neuronal substrate. One major distinction is between serial order information acquired intentionally and leading to explicit conscious knowledge of the sequence structure, and information acquired incidentally through experience. While this latter form of knowledge influences behaviour, it may do so without the participant being aware of the sequential information, i.e. it is acquired implicitly. Evidence from physiological and lesion studies in animals and imaging studies in humans suggests that these two forms of learning may have dissociable neuronal substrates. Specifically, the striato-thalamo-cortical circuit centred on the caudate nucleus is proposed to be involved in intentional sequence learning and that based on the putamen on incidental learning. The present study tested one part of this proposed dissociation by assessing patients with Huntington's disease on tasks of the two forms of learning. On the test of trial-and-error intentional learning there were marked deficits, which were closely related to disease progression and to measures of executive cognitive dysfunction. This finding was in contrast to the finding from the incidental learning task. Performance of the Huntington's disease group was essentially normal and unrelated to measures of disease progression and cognitive status. The results, although supportive of the proposed dual-system hypothesis, offer only partial confirmation. Further direct study is required using similar tasks in patients with putamenal disorder or lesions within the skeletomotor striato-thalamo-cortical circuit.

Adult↗

A longitudinal study of implicit and explicit memory in old persons.

Decline in explicit memory with advancing age is a common finding, but it is unclear whether implicit memory (repetition priming) declines or remains stable. Meta-analyses of studies that examined differences between extreme groups (young-old), typically at a single point in time and on a single test, suggest that a mild reduction in priming occurs with advancing age. The authors examined explicit memory and priming, on multiple tests over 4 annual data-collection waves, in a large group of older persons without dementia at baseline. Explicit memory declined significantly, but priming remained stable. Findings indicate that explicit memory and priming are dissociable on the basis of age-related change and that mildly reduced priming is not an inevitable consequence of growing older.

Aged↗

Effects of Parkinson disease on two putative nondeclarative learning tasks: probabilistic classification and gambling.

OBJECTIVE: To assess performance on two nondeclarative (implicit) memory tasks of Parkinson disease (PD) patients without dementia in the earlier or later stages of the disease (Hoehn and Yahr Scale scores of 1-2.5 or 3-4, respectively). BACKGROUND: Different subtypes of nondeclarative memory appear to depend on different components of frontostriatal circuitry. Performance on a probabilistic classification learning (PCL) task was impaired by striatal damage (eg, in PD or Huntington disease) but not by circumscribed frontal lobe damage. On the other hand, performance on the Iowa Gambling Task (IGT) was impaired by damage to the prefrontal cortex. METHOD AND RESULTS: On the PCL, the learning of the control (age- and education-matched) group (n = 19) and the early PD group (n = 16) was comparable with each other, and both groups showed better performance than the later PD group (n = 16). On the IGT, the control group learned better than both of the PD groups. The control and early PD groups were similar on measures from the Wisconsin Card Sorting Test, Stroop Test, Mini-Mental State Examination, and Beck Depression Inventory II. CONCLUSIONS: The PCL and IGT tasks appear to rely on different parts of the frontostriatal circuitry in patients with early PD. The current finding that IGT performance was impaired in early PD implies ventromedial prefrontal cortical dysfunction early in the disease.

Aged↗

[Influence of attention on an auditory-verbal learning test in schizophrenic patients].

Schizophrenic patients are known to feature alterations in their cognitive performances, principally in executive functions, attention and memory. In this last domain, studies have shown a relatively severe and global deficit, which can be assessed in chronic and first episode patients. It seems that the memory dysfunction is independent of age and intellectual level, but does correlate with negative psychopathology and global functioning. In the study of memory dysfunction, attentional capacities, information processing and symptomatology have to be considered as determining factors. It has been shown that patients with schizophrenia perform poorly in selective attention tasks and that this deficit may interfere with learning. In the same way, the slowing of information processing contributes to a superficial and incomplete learning. The impact of symptomatology has also to be considered, as negative and depressive symptoms are linked to mnesic performances. The majority of studies bearing on working memory and schizophrenia show an alteration of performances, but studies on long term memory are more equivocal. Procedural memory seems to be preserved, while declarative memory is impaired. These results support the hypothesis that in schizophrenia, memory processes that are consciously controlled are impaired, contrary to implicit learning which may be intact. Nevertheless, studies bearing on semantic memory and episodic memory show controversial results. Still, many authors argue that schizophrenic patients have difficulties in recalling learned material, specially when a delay or a interfering task are introduced in the test. Besides, the schizophrenic subjects do not use the semantic properties of the words, as well as the control subjects, when they have to learn a words list for example. The main goal of the present study was to examine the auditory-verbal learning capacities of 31 schizophrenic patients (20 men and 11 women, 19-56 years old), compared to 27 healthy subjects (11 men and 16 women, 23-56 years old). All subjects received an evaluation including the Rey Auditory-Verbal Learning Test, used to study the progressive acquisition of 15 disyllabic words which are successively orally presented five times to the subject. About forty-five minutes after the last of the five immediate recalls, the delayed recall is assessed and a percentage of retention is also calculated. Visual reasoning and attention capacities were studied with the Progressive Matrix and the d2 encumbrance test respectively. Global psychiatric symptomatology of the patients group was assessed with the Brief Psychiatric Rating Scale. Considering the literature existing on the verbal learning capacities of schizophrenic patients, it was expected that the patients would perform poorly and learn slower than controls. The initial learning of the material, which is a critical stage for schizophrenic patients, was studied with particular attention as well as the effect of the introduction of a delay upon the recall of the words list. A secondary objective of the study was to investigate the role of visual reasoning and attention upon auditory-verbal learning process. According to published studies, it is expected that schizophrenic patients manifest some impairment in the domains of visual reasoning and attention. The question is to know whether it alters performances in the auditory-verbal learning test or not. Finally, the links between clinical characteristics of the patients, like age and illness duration, and their learning performances were explored. Statistical analysis included first a descriptive analysis of data to examine differences between the two groups. Second, ANCOVAs were used in order to control the respective impact of educational level, attention capacities and verbal reasoning capacities upon learning performances. Third, Spearman's correlations were used to detect links between clinical characteristics of the patients and learning performances. The comparisons between patients and controls confirmed that schizophrenic patients scored less in the attentional and visual reasoning tasks. They also featured a lower educational level compared to the healthy subjects. In the auditory-verbal learning test, the patients showed altered performances in the five recalls, as well as in the delayed recall and for the retention percentage. In order to control the impact of educational level, attentional and visual reasoning capacities, these parameters were introduced in the statistical analyses. Educational level did not influence memory alterations in the schizophrenic group. However, attention and, to a lesser extend, visual reasoning had an impact on the comparison of memory scores: when controlling attention, almost no significant group effect remained. Finally, the exploratory analyses of links between clinical characteristics and memory only revealed the presence of a significant negative correlation between illness duration and learning performances. Thus, the analyze of data showed that schizophrenic subjects featured poor performances in the domains of attention, verbal reasoning and auditory-verbal memory. Further analyses taking into account group differences on attention suggest that the impairment featured by schizophrenic patients in the domain of verbal memory strongly relies on an attentional deficit. These results are discussed according to the existing literature and methodological limitations. Clinical implications are also discussed.

Adult↗

Reduced activation to implicit affect induction in euthymic bipolar patients: an fMRI study.

OBJECTIVE: To examine whether euthymic bipolar patients engage similar or contrasting brain regions as healthy subjects when responding to implicit affect induction. METHODS: The study examined 10 euthymic patients with bipolar I disorder, and 10 age- and gender-matched healthy subjects using event-related functional magnetic resonance imaging (fMRI) while subjects engaged in a modified word-based memory task designed to implicitly evoke negative, positive or no affective change. The activation paradigm involved nominating whether a target word was contained within a previously presented word list using specified response keys. RESULTS: The fMRI task produced significantly greater activation in healthy subjects as compared to patients in response to both negative and positive affect in the anterior and posterior cingulate, medial prefrontal cortex, middle frontal and right parahippocampal gyri. Only negative affect produced significantly greater activation in the postcentral gyrus, inferior parietal lobule, thalamus and putamen and only positive affect achieved the same in the precentral, superior temporal and lingual gyri, precuneus, cuneus, caudate, pons, midbrain and cerebellum. There were no brain regions in which responses were greater in patients as compared to healthy subjects. There were no statistically significant differences between the groups with respect to speed or accuracy. CONCLUSIONS: Diminished prefrontal, cingulate, limbic and subcortical neural activity in euthymic bipolar patients as compared to healthy subjects is suggestive of emotional compromise that is independent of cognitive and executive functioning. This finding is of clinical importance and has implications both for the diagnosis and treatment of bipolar disorder. Future studies should aim to replicate these findings and examine the development of bipolar disorder, investigating in particular the effects of medication.

Adult↗

Does PAULA prime PAUL? Does WAITER prime WAITRESS? Implicit transfer across gender forms of verbal stimuli.

Repetition-priming effects were investigated with a speeded verification task as an indirect or implicit test. Subjects were asked to verify whether items were instances of the categories "first name" and "profession." In Experiment 1, instances were repeated in their alternate gender form (e.g., PAUL as PAULA, or WAITRESS as WAITER) and performance was compared to new instances. Facilitation in terms of faster response latencies for old instances (i.e., repetitions in the alternative gender form) was restricted to the category "profession." In Experiment 2, facilitation was found for names studied and tested in the same gender form (e.g., PAUL-PAUL). Instances of professions were repeated in either the same or the alternative gender form; the amount of facilitation was identical for the two repetition conditions. However, transfer across gender forms was affected by the study-test order (facilitation was larger from male to female than from female to male) and by the gender dominance of specific instances. In Experiment 3, the interfering effect of gender dominance was not replicated. Response accuracy tended to parallel the latency results in all experiments, but without reaching statistical reliability. Therefore, the faster response latencies for old items are by no means the result of a speed-accuracy trade-off. The central finding of the experiments reported is the material-dependent dissociation of repetition transfer across gender forms that occurred for instances of professions, but was absent for names. This dissociation is interpreted to indicate that the stimulus-driven speeded verification test is sensitive to conceptual, but not to perceptual, processing aspects of a study event.

Adolescent↗

Involvement of the medial temporal lobe in priming for new associations.

This study was addressed to the question of whether the medial temporal lobe (MTL) plays a critical role in implicit memory for new associations. Priming for new associations was examined in two different tasks in 18 patients with focal lesions all involving the MTL. In Experiment 1, following a study phase for pairs of unrelated words, subjects performed a perceptual identification task on old, recombined, and new pairs of words presented at brief exposure durations. In contrast to control subjects, and despite a normal level of item priming, the patients failed to show superior identification of the old pairs relative to the recombined pairs, the measure of associative priming. In Experiment 2, subjects engaged in speeded naming of the print color for previously studied words presented in the original color or in a different old color, and for unstudied words. Again, in contrast to control subjects and despite a normal level of item facilitation on color naming reaction time (RT), the patients failed to show priming for recently experienced new associations between words and colors. Explicit recognition memory by the patients was abnormal in both experiments. This study records an absence of priming for new associations, in two different tasks in which the nature of the stimuli was considerably different, in a large group of patients with lesions in the MTL. Although some previous research has reported significant associative priming in other tasks for patients with MTL lesions, the present results suggest that this region is critical for forming new associations of the types assessed here.

Adolescent↗