Children's inhibition skills are associated with their P3a latency-results from an exploratory study.

BACKGROUND: The P3a response is thought to reflect involuntary orienting to an unexpected stimulus and has been connected with set-shifting and inhibition in some studies. In our exploratory study, we investigated if the amplitude and the latency of the P3a response were associated with the performance in a modified flanker task measuring inhibition and set-shifting in 10-year-old children (N = 42). Children participated in electroencephalography (EEG) measurement with an auditory multifeature paradigm including standard, deviating, and novel sounds. In addition, they performed a separate flanker task requiring inhibition and set-shifting skills. RESULTS: The P3a latencies for deviant sounds were associated with the reaction time reflecting inhibition: the shorter the response latencies were, the faster the reaction time was. The P3a latencies for novel sounds were not linked to the reaction times reflecting either inhibition or set-shifting. In addition, the magnitude of the P3a response was not associated with the performance in the flanker task. CONCLUSIONS: Our results suggest that P3a response latency and reaction speed reflecting inhibitory skills are based on shared neural mechanism. Thus, the present study brings new insight to the field investigating the associations between behavior and its neural indices.

Longitudinal effects of choir singing on aging cognition and wellbeing: a two-year follow-up study.

Introduction: While increasing evidence points toward the benefits of musical activities in promoting cognitive and emotional well-being in older adults, more longitudinal studies are needed to establish their long-term effects and uncover the mechanisms through which musical activities affect well-being. Most previous research has focused on instrumental musical activities, but little is currently known about the long-term effects of singing, even though neuroimaging evidence suggests that it is a versatile activity for the brain, involving a multitude of neural processes that are potentially beneficial for well-being. Methods: We conducted a 2-year follow-up study to assess aging-related changes in cognitive functioning and emotional and social well-being with self-report questionnaires and standardized tests in 107 older adult choir singers and 62 demographically matched non-singers. Data were collected at baseline (T1), and at 1-year (T2) and 2-year (T3) follow-ups using questionnaires on subjective cognitive functioning, depression, social engagement, and quality of life (QOL) in all participants and neuropsychological tests in a subgroup of participants (45 choir singers and 41 non-singers). Results: The results of linear mixed model analysis showed that in verbal flexibility (phonemic fluency task), the choir singers had higher scores already at T1 and showed no change over time, whereas the non-singers showed enhancement from T1 to T3. Furthermore, active retrieval of word knowledge (WAIS-IV Vocabulary task) showed significantly different changes from T1 to T2 between the groups (enhancement in choir singers and decline in non-singers), however lacking significant change within groups. Similar opposite trajectories of QOL related to social inclusion and safety of the environment (WHOQOL-Bref Environmental subscale) were significant from T1 to T3, but these changes were not significant within groups or at each timepoint. Within the choir singers, shorter experience in choir singing was associated with greater improvement in the vocabulary task over the follow-up period, suggesting that initiation of choir singing at older age induces some verbal benefits. There were no group differences in any other questionnaire or neuropsychological measure over time. Discussion: In conclusion, our results suggest that choir singing at older age is associated with a sustained enhancement of phonemic fluency, while the effects on other verbal skills and quality of life are less clear.

Context independent reductions in external processing during self-generated episodic social cognition.

Ongoing cognition supports behavioral flexibility by facilitating behavior in the moment, and through the consideration of future actions. These different modes of cognition are hypothesized to vary with the correlation between brain activity and external input, since evoked responses are reduced when cognition switches to topics unrelated to the current task. This study examined whether these reduced evoked responses change as a consequence of the task environment in which the experience emerges. We combined electroencephalography (EEG) recording with multidimensional experience sampling (MDES) to assess the electrophysiological correlates of ongoing thought in task contexts which vary on their need to maintain continuous representations of task information for satisfactory performance. We focused on an event-related potential (ERP) known as the parietal P3 that had a greater amplitude in our tasks relying on greater external attention. A principal component analysis (PCA) of the MDES data revealed four patterns of ongoing thought: off-task episodic social cognition, deliberate on-task thought, imagery, and emotion. Participants reported more off-task episodic social cognition and mental imagery under low external demands and more deliberate on-task thought under high external task demands. Importantly, the occurrence of off-task episodic social cognition was linked to similar reductions in the amplitude of the P3 regardless of external task. These data suggest the amplitude of the P3 may often be a general feature of external task-related content and suggest attentional decoupling from sensory inputs are necessary for certain types of perceptually-decoupled, self-generated thoughts.

Myelination in mouse dorsal root ganglion/Schwann cell cocultures.

The established protocols for in vitro studies of peripheral nerve myelination with rat embryonic dorsal root ganglia (DRG) and postnatal Schwann cell cocultures do not work with mouse cells. Consequently, the full potential of this model, which would allow to perform cell type-specific, mixed genotype cocultures without cross-breeding the animals, cannot be exploited. We determined the conditions required to promote full myelination in cocultures of pre-purified mouse embryonic DRG and neonatal Schwann cells, and present a method which consistently yields 50-200 mature myelin sheaths/culture. Causes for the failure of the existing protocols to yield satisfactory results with mouse cells fell into three categories: the lack of adherent support provided by the substratum, growth factor and hormone deficiencies, and the high serum content of the media. For optimal results, mouse cocultures require a 3-dimensional substratum, a myelination-promoting culture medium containing pituitary extract, N2 supplement and forskolin, and a low serum concentration.

Isolation, purification and expansion of myelination-competent, neonatal mouse Schwann cells.

Most studies of peripheral nerve myelination using culture models are performed with dorsal root ganglion neurons and Schwann cells pre-purified from the rat. The potential of this model is severely compromised by the lack of rat myelin mutants and the published protocols work poorly with mouse cells, for which numerous myelin mutants are available. This is partly due to difficulties in obtaining sufficient quantities of myelination-competent mouse Schwann cells. Here, we describe the isolation, purification and expansion of wild-type, myelination-competent Schwann cells from the sciatic nerves of 4-day-old mouse pups. The method consistently yields 1.9-3.3 x 10(6) of approximately 95% pure Schwann cells from the sciatic nerves of 12-15 4-day-old mouse pups, within 14-20 days. The Schwann cell proliferation rate ranges from 2.7- to 4.30-fold growth/week. Proliferation ceases within 4 weeks, when the cells become quiescent. Growth is reinduced by the presence of neurons; neuregulin is not sufficient for this effect. The Schwann cells isolated by this protocol are able to form compact myelin in culture, as judged by the segregated expression patterns of early (myelin-associated glycoprotein) and late (myelin basic protein) myelination markers in a three-dimensional neuron/Schwann cell coculture model. The Schwann cell batch yields are sufficient to perform 100-150 individual myelinating coculture assays. Employing mixed phenotype/genotype mouse neuron/Schwann cell cocultures, it will be possible to analyse the cell specificity of a mutation, and the cumulative effects of different mutations, without having to cross-breed the animals.

Degraded myelin-associated glycoprotein (dMAG) formation from pure human brain myelin-associated glycoprotein (MAG) is not mediated by calpain or cathepsin L-like activities.

The myelin-associated glycoprotein (MAG) is a transmembrane cell adhesion molecule participating in myelin formation and maintenance. Calcium-activated/-dependent proteolysis of myelin-associated glycoprotein by calpain and cathepsin L-like activities has already been detected in purified myelin fractions, producing a soluble fragment, called degraded (d)MAG, characterized by the loss of the transmembrane and cytoplasmic domains. Here, we demonstrate and analyze dMAG formation from pure human brain myelin-associated glycoprotein. The activity never exhibited the high rate previously reported in human myelin fractions. Degradation is time-, temperature-, buffer- and structure-dependent, is inhibited at 4 degrees C and by denaturation of the sample, and is mediated by a trans-acting factor. There is no strict pH dependency of the proteolysis. Degradation was inhibited by excess aprotinin, but not by 1-10 micro g/mL aprotinin and was not eliminated by the use of an aprotinin-sepharose matrix during the purification. dMAG formation was not enhanced by calcium, nor inhibited by a wide variety of protease inhibitors, including specific calpain and cathepsin L inhibitors. Therefore, while cysteine proteases may be present in human myelin membrane fractions, they are not involved in dMAG formation from highly purified human brain myelin-associated glycoprotein preparations.