Biomedical subjects

Andrea Berger

Publications and source records attributed to Andrea Berger.

13 recordsLinked to original sources

PubMed2007

Large-scale mapping of mutations affecting zebrafish development.

BACKGROUND: Large-scale mutagenesis screens in the zebrafish employing the mutagen ENU have isolated several hundred mutant loci that represent putative developmental control genes. In order to realize the potential of such screens, systematic genetic mapping of the mutations is necessary. Here we report on a large-scale effort to map the mutations generated in mutagenesis screening at the Max Planck Institute for Developmental Biology by genome scanning with microsatellite markers. RESULTS: We have selected a set of microsatellite markers and developed methods and scoring criteria suitable for efficient, high-throughput genome scanning. We have used these methods to successfully obtain a rough map position for 319 mutant loci from the Tübingen I mutagenesis screen and subsequent screening of the mutant collection. For 277 of these the corresponding gene is not yet identified. Mapping was successful for 80 % of the tested loci. By comparing 21 mutation and gene positions of cloned mutations we have validated the correctness of our linkage group assignments and estimated the standard error of our map positions to be approximately 6 cM. CONCLUSION: By obtaining rough map positions for over 300 zebrafish loci with developmental phenotypes, we have generated a dataset that will be useful not only for cloning of the affected genes, but also to suggest allelism of mutations with similar phenotypes that will be identified in future screens. Furthermore this work validates the usefulness of our methodology for rapid, systematic and inexpensive microsatellite mapping of zebrafish mutations.

Animals↗

PubMed2006

Infant brains detect arithmetic errors.

A current debate is whether increased looking time in infancy is related to violation of expectations. In this study, 6- to 9-month-old infants' brain activity was analyzed during presentation of correct and incorrect solutions to simple arithmetic equations [(e.g., presentation of 1 + 1; one doll on a TV monitor, with another doll added from behind a screen, followed by a solution of 2 (correct) or 1 (incorrect)]. Infants looked longer at incorrect solutions than at correct ones. Event-related potentials, time-locked to the presentation of the solution, also differed between conditions, with greater negative activity for the incorrect solution condition. Spectral analysis showed a similar pattern to that of adults observing correct and incorrect arithmetical equations. These findings show (i) that the brain network involved in error detection can be identified in infancy and (ii) that this network can support an association between looking time and violation of expectations.

Adult↗

PubMed2006

Coding region paraoxonase polymorphisms dictate accentuated neuronal reactions in chronic, sub-threshold pesticide exposure.

Organophosphate pesticides (OPs), known inhibitors of acetylcholinesterase (AChE), are used extensively throughout the world. Recent studies have focused on the ACHE/PON1 locus as a determinant of inherited susceptibility to environmental OP exposure. To explore the relationship of the corresponding gene-environment interactions with brain activity, we integrated neurophysiologic, neuropsychological, biochemical, and genetic methods. Importantly, we found that subthreshold OP exposure leads to discernible physiological consequences that are significantly influenced by inherited factors. Cortical EEG analyses by LORETA revealed significantly decreased theta activity in the hippocampus, parahippocampal regions, and the cingulate cortex, as well as increased beta activity in the prefrontal cortex of exposed individuals-areas known to play a role in cholinergic-associated cognitive functions. Through neuropsychological testing, we identified an appreciable deficit in the visual recall in exposed individuals. Other neuropsychological tests revealed no significant differences between exposed and non-exposed individuals, attesting to the specificity of our findings. Biochemical analyses of blood samples revealed increases in paraoxonase and arylesterase activities and reduced serum acetylcholinesterase activity in chronically exposed individuals. Notably, specific paraoxonase genotypes were found to be associated with these exposure-related changes in blood enzyme activities and abnormal EEG patterns. Thus, gene-environment interactions involving the ACHE/PON1 locus may be causally involved in determining the physiological response to OP exposure.

Acetylcholinesterase↗

PubMed2006

Individual performance based on cognitive experimental measurements? The case of inhibition of return.

Inhibition of Return (IOR) is a mechanism whereby the attentional system favors novel locations by inhibiting already scanned ones. In spatial attention tasks, it commonly occurs when the interval between cue onset and target onset is longer than 300 ms. The positive difference between reactions in the valid condition and those in the invalid one shows that responses to target stimuli are slower following a valid cue than responses to target stimuli following an invalid cue. IOR is a very robust phenomenon at the group mean level; however, this study demonstrates that its standard error of measurement is extremely high, which seriously challenges any attempt to interpret an individual score as representing the characteristics of a subject's attention system. Furthermore, this reliability problem might diminish the likelihood of finding differences between groups and conditions. The study shows that these problems may be partially corrected by employing the back-to-center paradigm.

Attention↗

PubMed2006

Motor inhibition and learning impairments in school-aged children following exposure to organophosphate pesticides in infancy.

Despite the critical role of acetylcholinesterase (AChE) in cortical function and development, no long-term studies have been conducted in humans on the long-term sequelae of the disruption of the cholinergic system in early childhood. We report a neuropsychological assessment of healthy school-aged children, who had been hospitalized in infancy following exposure to organophosphate pesticides, compared with children exposed to other toxins such as kerosene, and age- and sex-matched non-exposed children. Although overall, the children seem to have overcome the acute one-time exposure incident, and they all attend regular schools, a finer assessment of specific cognitive abilities indicates they are impaired compared with the matched controls. Specifically, the children who had been exposed to organophosphate pesticides had a deficit in inhibitory motor control. Children with pesticide or kerosene poisoning had a retrieval deficit on the acquisition phase of a verbal learning task.

Case-Control Studies↗

PubMed2005

Analysis of word clustering in verbal fluency of school-aged children.

The use of clustering strategies in semantic and phonological fluency was tested in children in third (age 8-9) and fifth (age 10-11) grades. To analyze the development of clustering strategies in the fluency task, the latency to the first word and intervals between clustered and non-clustered words were recorded. Semantic fluency was greater than phonological fluency in both age groups. Children in fifth grade had greater semantic and phonological fluency than children in the third grade, concomitant with an increase in number of clusters, but not in cluster size. The greater facility of the children with semantic fluency was confirmed by a shorter latency to the first word, and significantly shorter intervals between clustered words compared to non-clustered words. Girls had shorter latencies to the first word and made more phonological clusters in the semantic task than boys. The increase in cluster number and concomitant increase in fluency in older children might be related to the development of cognitive flexibility. These data suggest that measurement of clustering strategies in the verbal fluency task can be used to assess executive function deficits in children with acquired or developmental neurological impairment or attention deficits.

Age Factors↗

PubMed2005

Competition between endogenous and exogenous orienting of visual attention.

The relation between reflexive and voluntary orienting of visual attention was investigated with 4 experiments: a simple detection task, a localization task, a saccade toward the target task, and a target identification task in which discrimination difficulty was manipulated. Endogenous and exogenous orienting cues were presented in each trial and their validity was manipulated orthogonally to examine whether attention mechanisms are mediated by separate systems and whether they have additive and independent effects on visual detection and discrimination. The results showed that each orienting mechanism developed its typical and independent effect in every case except for the difficult identification task. A theoretical framework for understanding the relationship between endogenous and exogenous orienting of attention is proposed, tested, and confirmed.

Attention↗

PubMed2005

Task switching after cerebellar damage.

The authors of this study investigated task switching following cerebellar damage. The study group consisted of 7 children and adolescents (M age=13.8 years) who underwent surgical removal of a benign posterior fossa tumor. They were tested at a sufficient interval after surgery (M lag=6.13 years) for restoration of normal cognitive skills and intelligence. Although all showed normal learning of the task compared with control participants, when rapid behavioral changes were required (short preparation time), they exhibited behavioral rigidity manifested by enhanced switching cost. These results are in line with another study on serial reaction time with the same patients (A. Berger et al., in press). They have important implications for our understanding of the cognitive sequelae of early cerebellar damage as well as the involvement of the cerebellum in task switching.

Adolescent↗

PubMed2005

Neuropsychology of vitamin B12 deficiency in elderly dementia patients and control subjects.

Cobalamin deficiency may cause cognitive deficits and even dementia. In Alzheimer's disease, the most frequent cause of dementia in elderly persons, low serum levels of vitamin B12, may be misleading. The aim of this work was to characterize the cognitive pattern of B12 deficiency and to compare it with that of Alzheimer's disease. Nineteen patients with low levels of vitamin B12 were neuropsychologically evaluated before treatment and a year later. Results were compared with those of 10 healthy control subjects. Final results suggest that there is a different pattern in both diseases. Twelve elderly patients with dementia improved with treatment. Seven elderly demented patients did not improve; they deteriorated after 1 year although their levels of cobalamin were normal. Analysis of the initial evaluation showed that the 2 groups of patients had a different neuropsychological profile. The group that improved had initially more psychotic problems and more deficits in concentration, visuospatial performance, and executive functions. They did not show language problems and ideomotor apraxia, which were present in the second group. Their memory pattern was also different. These findings suggest that cobalamin deficiency may cause a reversible dementia in elderly patients. This dementia may be differentiated from that of Alzheimer's disease by a thorough neuropsychological evaluation.

Aged↗

PubMed2005

Motor and non-motor sequence learning in children and adolescents with cerebellar damage.

Cerebellar involvement in motor and non-motor sequence learning was examined with serial reaction time tasks (SRT). Our sample consisted of 8 children and adolescents who had undergone surgical removal of a benign posterior fossa tumor (PFT) during childhood. None of them had undergone chemotherapy or cranial radiation therapy (CRT). Ages ranged from 1-11 years at surgery and 9-17 years at testing. The children were tested not earlier than 2.5 years after surgery (M = 5.9 years), enabling brain plasticity and recovery of functions. Their performance was compared with a matched control sample. The PFT group was not impaired in the implicit learning of sequences, as reflected in their performance in blocks with a repeated sequence, both before and after a random block. However, in the perceptual task, their performance deteriorated more than that of the control group when a random block was introduced, suggesting that it was more difficult for the patients to respond flexibly or change their response set when encountering changing task demands. These results are in line with another study by our group on task switching with the same patients.

Adolescent↗

PubMed2004

Benign familial infantile convulsions: linkage to chromosome 16p12-q12 in 14 families.

PURPOSE: Benign familial infantile convulsions (BFIC) is a form of idiopathic epilepsy. It is characterized by clusters of afebrile seizures occurring around the sixth month of life. The disease has a benign course with a normal development and rare seizures in adulthood. Previous linkage analyses defined three susceptibility loci on chromosomes 19q12-q13.11, 16p12-q12, and 2q23-31. However, a responsible gene has not been identified. We studied linkage in 16 further BFIC families. METHODS: We collected 16 BFIC families, without an additional paroxysmal movement disorder, of German, Turkish, or Japanese origin with two to eight affected individuals. Standard two-point linkage analysis was performed. RESULTS: The clinical picture included a large variety of seizure semiologies ranging from paleness and cyanosis with altered consciousness to generalized tonic-clonic seizures. Interictal EEGs showed focal epileptiform discharges in six patients, and three ictal EEGs in three distinct patients revealed a focal seizure onset in different brain regions. In all analyzed families, we found no evidence for linkage to the BFIC loci on chromosomes 19q and 2q, as well as to the known loci for benign familial neonatal convulsions on chromosomes 8q and 20q. In 14 of the families, the chromosome 16 locus could be confirmed with a cumulative maximum two-point lod score of 6.1 at marker D16S411, and the known region for BFIC could be narrowed to 22.5 Mbp between markers D16S690 and D16S3136. CONCLUSIONS: Our data confirm the importance of the chromosome 16 locus for BFIC and may narrow the relevant interval.

Adolescent↗

PubMed2004

Emerging developmental pathways to ADHD: possible path markers in early infancy.

Sixty-six male infants participating in the Ben-Gurion Infant Development Study of familial risk for attention deficit hyperactivity disorder (ADHD) were assessed at 7 months of age using observational and mother report measures. Risk for ADHD was based on ADHD symptoms in the father. Infants whose fathers had seven or more symptoms formed the ADHD risk group; infants whose fathers had three or less symptoms formed the comparison group. The ADHD risk group significantly differed from the comparison group on measures of interest, anger, and activity level and showed less interest in block play and more anger reactivity but less directed anger in a barrier task. According to mother report, the ADHD risk group had higher levels of activity than the comparison group. Measures of neonatal immaturity and activity were related to behavior at 7 months. The findings suggest that possible developmental pathways to ADHD may be emerging in early infancy.

Anger↗

PubMed2002

The development of internal representations of magnitude and their association with Arabic numerals.

Developmental aspects of number concepts were evaluated using participants from the beginning and end of first grade (6-7 years old), third and fifth grades (7-11 years old), and university (22 years old). Participants evaluated the numerical value or physical size of stimuli varying along both dimensions. The numerical distance effect appeared in all groups. In contrast, the size congruity effect started to appear only at the end of first grade. Based on our results, a model of internal representation of magnitude claiming that there are two different representations was propose. At the beginning of first grade children can automatically access only one of these representations and only from the end of first grade can they access both of these representations.

Adult↗