Neuronal pattern separation of motion-relevant input in LIP activity.

In various regions of the brain, neurons discriminate sensory stimuli by decreasing the similarity between ambiguous input patterns. Here, we examine whether this process of pattern separation may drive the rapid discrimination of visual motion stimuli in the lateral intraparietal area (LIP). Starting with a simple mean-rate population model that captures neuronal activity in LIP, we show that overlapping input patterns can be reformatted dynamically to give rise to separated patterns of neuronal activity. The population model predicts that a key ingredient of pattern separation is the presence of heterogeneity in the response of individual units. Furthermore, the model proposes that pattern separation relies on heterogeneity in the temporal dynamics of neural activity and not merely in the mean firing rates of individual neurons over time. We confirm these predictions in recordings of macaque LIP neurons and show that the accuracy of pattern separation is a strong predictor of behavioral performance. Overall, results propose that LIP relies on neuronal pattern separation to facilitate decision-relevant discrimination of sensory stimuli.NEW & NOTEWORTHY A new hypothesis is proposed on the role of the lateral intraparietal (LIP) region of cortex during rapid decision making. This hypothesis suggests that LIP alters the representation of ambiguous inputs to reduce their overlap, thus improving sensory discrimination. A combination of computational modeling, theoretical analysis, and electrophysiological data shows that the pattern separation hypothesis links neural activity to behavior and offers novel predictions on the role of LIP during sensory discrimination.

Maximum likelihood estimators for truncated and censored power-law distributions show how neuronal avalanches may be misevaluated.

The coordination of activity amongst populations of neurons in the brain is critical to cognition and behavior. One form of coordinated activity that has been widely studied in recent years is the so-called neuronal avalanche, whereby ongoing bursts of activity follow a power-law distribution. Avalanches that follow a power law are not unique to neuroscience, but arise in a broad range of natural systems, including earthquakes, magnetic fields, biological extinctions, fluid dynamics, and superconductors. Here, we show that common techniques that estimate this distribution fail to take into account important characteristics of the data and may lead to a sizable misestimation of the slope of power laws. We develop an alternative series of maximum likelihood estimators for discrete, continuous, bounded, and censored data. Using numerical simulations, we show that these estimators lead to accurate evaluations of power-law distributions, improving on common approaches. Next, we apply these estimators to recordings of in vitro rat neocortical activity. We show that different estimators lead to marked discrepancies in the evaluation of power-law distributions. These results call into question a broad range of findings that may misestimate the slope of power laws by failing to take into account key aspects of the observed data.

Abnormal strategies during visual discrimination reversal learning in ephrin-A2(-/-) mice.

Eph receptors and ephrins are involved in establishing topographic connectivity in primary sensory brain regions, but also in higher order structures including the cortex and hippocampus. Ephrin-A2(-/-) mice have abnormal topography in the primary visual system but have normal visual and learning performance on a simple visual discrimination task. Here we use signal detection theory to analyse learning behaviour of these mice. Wild-type (WT) and ephrin-A2(-/-) (KO) mice performed equally well in a two-stimulus visual discrimination task, with similar learning rates and response latencies. However, during reversal learning, when the rewarded stimulus was switched, the two genotypes exhibited differences in response strategies: while WTs favoured a win-stay strategy, KOs remained relatively neutral. KOs also exhibited a stronger lateralization bias in the initial stages of learning, choosing the same arm of the maze with high probability. In addition, use of a Bayesian "optimal observer" revealed that compared to WT, KO mice adapted their decisions less rapidly to a change in stimulus-reward relationship. We suggest that the misexpression of ephrin-A2 may lead to abnormal connectivity in regions known for their involvement in reversal learning and perseverative behaviours, including thalamic-prefrontal cortical-striatal circuitry and particularly orbitofrontal cortex. The implication is that topographic organisation of higher order brain regions may play an important role in learning and decision making.

Recognition of incomplete patterns by bumble bees.

Bumble bees were trained to discriminate between two visual patterns, one of which was rewarding (S+) and one of which was unrewarding (S-). Subsequently, they were tested for discrimination between two non-rewarding patterns: the top halves of the training patterns, the bottom halves or the side halves. Three conditions were tested: (1) When the S+ was a star and the S- was a circle, all halves of the star were chosen above chance level, which may reflect an unlearned preference for radial patterns. (2) When the S+ and S- were reversed, the bottom half and the side half of the circle were chosen above chance level, but not the top half. (3) In the last condition, the S+ was again a circle, but the feeder tube was placed below the training pattern rather than above, and again the bottom halves were discriminated but neither the top nor the side halves were. In learning pattern discriminations, the ventral portion of the pattern is weighted more strongly than the dorsal portion, which enables recognition of incomplete patterns, and the weighting depends little on angle of approach.

Prolongation of brainstem auditory-evoked responses in autistic probands and their unaffected relatives.

BACKGROUND: Brain function, as indexed by brain electrical activity, is heritable in humans, and it may be impaired in autism. Autism also has strong genetic determinants, and like all major psychiatric disorders, its complex clinical phenotype renders genetic studies difficult. Innovative strategies focused on alternative biological phenotypes are needed. METHODS: The early brain auditory-evoked response was assessed in 73 autistic probands and 251 relatives who were compared with 521 normal controls. RESULTS: We first confirmed in the autistic probands the presence of a slowing in nerve conduction in the auditory system as expressed by the prolongation of early brain auditory-evoked response under the form of I-III interpeak latencies (IPLs). Furthermore, we observed the same I-III IPL prolongation in the unaffected first degree relatives of the autistic probands compared with controls. Despite clear evidence of a coaggregation of autism and I-III IPL prolongation in families, the IPLs did not seem to be the sole liability factor for autism as suggested by the observation of 52% of families in which the autistic proband and relatives showed normal IPLs. CONCLUSION: A prolongation of the early brain auditory-evoked response IPLs may be a marker for one of several deficits underlying autism and deserves further analysis as a potential alternative phenotype for the disorder.

[Clinical report on pharmacological treatment of autism]. / Note clinique sur le traitement pharmacologique de l'autisme.

This article reviews the pharmacology of autism and briefly overviews its use, history and novelties. "Autism" does not refer to any pathophysiology currently known. And no drug or class of drugs can cure this illness which includes many. Before using drugs, efficient in relieving symptoms, it is important to consider the potential benefit of behavioral approaches. Developments in research give hope that drugs will cure or prevent this brain illness.

Family history of cognitive disabilities in first-degree relatives of autistic and mentally retarded children.

We compared with a family history method the rate of cognitive disabilities (CD) in 156 first-degree relatives of 49 autistic (AU) probands to that found in 55 first-degree relatives of 18 mentally retarded (MR) probands. Broadly defined CD were found in, respectively, 17 and 16% of the relatives of the AU and MR probands. However, the characteristics of the probands associated with a family history of CD are different in AU and MR: Female and low IQ AU probands have more first-degree relatives with CD. Our findings suggest that a positive family history of CD is not specific to autism when compared to mental retardation. The observation that female and low IQ probands have higher family history of CD may suggest heterogeneity within autistic children and provides leads for future family studies.

Genetic analysis of genealogies in mentally retarded autistic probands from Saguenay Lac-Saint-Jean (Quebec, Canada).

Autism is a heterogeneous disorder for which we have evidence of both genetic and environmental determination. The genealogies of 16 autistic probands born in Saguenay Lac-Saint Jean were reconstructed and compared to those of 48 matched control individuals distributed in three different groups. The mean inbreeding and kinship coefficients were calculated. Both coefficients were not found to be increased in the autistic group compared to the control groups. These findings support the conclusions reached by Jorde et al. (1990) which indicated that a single gene was unlikely to account for most cases of autism.

Brainstem auditory evoked response and subcortical abnormalities in autism.

Previous studies of the neurobiology of autism that have used the brainstem auditory evoked response have given contradictory results. The authors of this study considered two supplementary aspects; they added an ipsilateral masking procedure, and they compared the results for every subject to the values (corrected for age and sex) of a large number of normal children. Twenty autistic (according to DSM-III-R criteria) and 13 mentally retarded (nonverbal IQ less than 75) subjects were assessed. Eighty percent of the autistic subjects had abnormal interpeak latencies, compared to 15% of the mentally retarded subjects. The I-V and III-V prolonged interpeak latency values were seen only in the autistic subjects. The ipsilateral masking procedure doubled the rate of detection of higher-brainstem abnormalities in the autistic children.

Psychiatric status of adolescents who had extreme temperaments at age 7.

Two temperamentally extreme (extremely easy and extremely difficult) subgroups of children were selected at the age of 7 years from a large random sample of the general population of Quebec City. The clinical status, family functioning, IQ, and academic performance of these children were reassessed at 12 and 16 years of age. Findings suggest that extreme temperament at age 7 predicts psychiatric status in preadolescence and adolescence only when family functioning is also taken into account. The adolescents who had been temperamentally difficult children and who were living in families with dysfunctional behavior control displayed more clinical disorders.

Brain-stem auditory evoked response: normative values in children.

Normative values of brain-stem auditory evoked response (BAER) derived from a large (N = 174) normal school age sample are presented. In our 4-14 years of age sample we found a significant influence of sex on some BAER components, and a significant influence of age on others. The norms have been computed according to these influences. Particular aspects of the influence of age and sex are also discussed.

Extreme temperament and diagnosis. A study in a psychiatric sample of consecutive children.

We report on an epidemiological-clinical study of the New York (NY) Longitudinal Study temperament model in a consecutive sample of children (N = 814) referred to a child psychiatric center. Temperament comparisons in this clinical population were made by using temperament normative values obtained in previous random samples of the general population in the greater Quebec City (Canada) area. Different clinical diagnostic groups (externalized disorders, developmental delays, and mixed disorders) were derived from a review of the entire hospital charts in which the interrater reliability was tested and performed "blind" to temperament scores. The diagnostic groups were confirmed through discriminant function analyses. The results (1) replicated, in this child psychiatric population, two factors of temperament similar to those previously found in random samples of our general population; (2) showed, in the psychiatric population of children, an overproportion of difficult temperaments on both factors; (3) confirmed conversely that a large proportion of children referred for a disorder did not present with an extreme temperament, and, therefore, an extreme temperament and a clinical disorder were not equivalent; and (4) suggested a specificity in the relationship between particular temperament factors and the type of clinical problem. Temperament factor 1 (withdrawal from new stimuli, low adaptability, high intensity, and negative mood) was found to be more associated with externalized disorders (opposition, conduct, or attention-deficit disorders), whereas temperament factor 2 (low persistence, high sensory threshold, and high mobility) was found to be more associated with specific developmental delays. The findings provided leads for future clinical research on temperament, family functioning, and child psychiatric diagnoses.

DNA microstructural requirements for neocarzinostatin chromophore-induced direct strand cleavage.

The microstructural requirements for optimal interaction of neocarzinostatin chromophore (NCS-C) with DNA have been investigated using a series of hexadeoxyribonucleotides with modified bases such as O6-methyl G (MeG), I, 5-methyl C (MeC), U, or 5-Bromo U (BrU) at specific sites in its preferred trinucleotide 5'GNaNb3':5'Na,Nb,C3' (Na = A, C, or T). Results show that MeG:C and G:MeC in place of G:C improve direct strand cleavage at the target Nb (Nb = T greater than A much greater than C greater than G), whereas MeC:G and C:MeG in place of Na:Nb, hinder cleavage. The optimal base target at Nb appears to be determined by its ability to form T:A type base pairing instead of C:G type. The observed differences in DNA strand cleavage patterns can be rationalized by induced changes in target site structure and are compatible with a model for NCS-C:DNA interaction in which the naphthoate moiety intercalates between 5'GNa3', and the activated tetrahydro-s-indacene, lying in the minor groove, abstracts a hydrogen atom from C-5' of Nb.

Significance of extreme temperament in infancy for clinical status in pre-school years. I: Value of extreme temperament at 4-8 months for predicting diagnosis at 4.7 years.

The relationship between extreme temperament in infancy and clinical status at 4.7 years of age was studied in temperamentally different groups of infants matched for sex and SES, and subselected from a large birth cohort representative of the general population. The effects of certain dimensions of family functioning and of other risk factors were examined. By itself, extremely difficult temperament in infancy had no strong direct association with clinical outcome at four years of age, whereas temperament assessed at four, family attitudes to discipline, and stressful events did. However, extreme temperament in infancy might indirectly affect outcome through its association with temperament at four. The interplay between adverse temperament and parental attitudes of discipline previously observed in middle childhood might have antecedents in pre-school years.

Significance of extreme temperament in infancy for clinical status in pre-school years. II: Patterns of temperament change and implications for the appearance of disorders.

Few, if any, of children's behavioural or cognitive characteristics assessed in the first years of life demonstrate stability until later childhood; early characteristics have so far failed to show an association with future psychopathology. This longitudinal study, from 4-8 months to 4.7 years old, focused on stability and change of extreme temperamental traits in groups of infants subselected from a large birth cohort. Persistent extreme temperament at four and eight months old did not increase stability of temperament to four years of age, relative to other children in the whole population. Sizeable change occurred, and the environmental parameters associated with negative temperamental change did not seem to be the same as those related to positive change. Boys with extreme scores were more stable, while girls appeared more prone to positive change. It is hypothesised that the direction of temperamental change in the first years could be more meaningful for long-term prediction of disorders than any one assessment of temperament taken at any one year.

Specific binding of o-phenanthroline at a DNA structural lesion.

DNA intercalators are found to recognize a DNA lesion as a high affinity receptor site. This lesion-specific binding is observed when one strand of a DNA double helix contains an extra, unpaired nucleotide. Our assay for binding controls for the effects of sequence with a series of oligodeoxynucleotide duplexes which are identical except for the location of the lesion, an extra cytidine. Scission of the series of oligodeoxynucleotides by the cuprous complex of ortho-phenanthroline (OP-Cu) indicates that OP-Cu binds at the lesion-specific stable intercalation site, suggesting that OP-Cu intercalates into DNA. The dispersion of OP-Cu scission sites over three residues is consistent with scission via a diffusible intermediate. The location of the scission sites, directly on the 3' side of the lesion, is consistent with minor groove binding in B DNA.

Cognitive development and reading achievement in pervasive-add, situational-add and control children.

Studies on hyperactivity have shown the importance of distinguishing hyperactive children according to the pervasiveness of their symptoms. To verify the meaningfulness of this distinction in Attention Deficit Disorders, an epidemiological study was undertaken. Sixteen pervasive-ADD, nine situational-ADD and 28 non-ADD children selected from a general population were compared using different measures. The results show that pervasive-ADD differ from non-ADD children on verbal IQ and reading difficulties and support the distinction of ADD according to the pervasiveness of the symptoms.

Auditory evoked potential and psychiatry.

An adolescent was implied in a car accident in which he suffered a head trauma without any substantial loss of consciousness. The posttraumatic syndrome was characterized by headaches and mental symptoms: nervousness, feelings of depersonalization, impaired memory, difficulty in concentration. Neurological examination and laboratory tests have always been normal but for a large perduring asymmetry at the Cortical Auditory Evoked Response. This finding is commented in the light of a review of the literature and of some neuropsychological findings.

Brain-stem auditory evoked response (BAER): normative study in children and adults.

The influences of age and sex on the BAER latency values are analysed in a non-clinical sample of adults and children. We found (1) that BAER values vary according to age and sex, but for the III-V interpeak latency (IPL); (2) that the age effect is more important than the sex effect on absolute latency (AL) II, III and V; (3) that there is a significant sex effect on the I-III IPL. Comparisons to other studies are made: we find differences but no contradiction. This is briefly discussed.