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Driving is a complex task concurrently drawing on multiple cognitive resources. Yet, there is a lack of studies investigating interactions at the brain-level among different driving subtasks in dual-tasking. This study investigates how visuospatial attentional demands related to increased driving difficulty interacts with different working memory load (WML) levels at the brain level. Using multichannel whole-head high density functional near-infrared spectroscopy (fNIRS) brain activation measurements, we aimed to predict driving difficulty level, both separate for each WML level and with a combined model. Participants drove for approximately 60 min on a highway with concurrent traffic in a virtual reality driving simulator. In half of the time, the course led through a construction site with reduced lane width, increasing visuospatial attentional demands. Concurrently, participants performed a modified version of the -back task with five different WML levels (from 0-back up to 4-back), forcing them to continuously update, memorize, and recall the sequence of the previous ' ' speed signs and adjust their speed accordingly. Using multivariate logistic ridge regression, we were able to correctly predict driving difficulty in 75.0% of the signal samples (1.955 Hz sampling rate) across 15 participants in an out-of-sample cross-validation of classifiers trained on fNIRS data separately for each WML level. There was a significant effect of the WML level on the driving difficulty prediction accuracies [range 62.2-87.1%; χ (4) = 19.9, < 0.001, Kruskal-Wallis test] with highest prediction rates at intermediate WML levels. On the contrary, training one classifier on fNIRS data across all WML levels severely degraded prediction performance (mean accuracy of 46.8%). Activation changes in the bilateral dorsal frontal (putative BA46), bilateral inferior parietal (putative BA39), and left superior parietal (putative BA7) areas were most predictive to increased driving difficulty. These discriminative patterns diminished at higher WML levels indicating that visuospatial attentional demands and WML involve interacting underlying brain processes. The changing pattern of driving difficulty related brain areas across WML levels could indicate potential changes in the multitasking strategy with level of WML demand, in line with the multiple resource theory.

Neuregulin-1 (NRG1) is one of the susceptibility genes for schizophrenia and implicated in the neurotrophic regulation of GABAergic and dopaminergic neurons, myelination, and NMDA receptor function. Postmortem studies often indicate a pathologic association of increased NRG1 expression or signaling with this illness. However, the psychobehavioral implication of NRG1 signaling has mainly been investigated using hypomorphic mutant mice for individual NRG1 splice variants. To assess the behavioral impact of hyper NRG1 signaling, we generated and analyzed two independent mouse transgenic (Tg) lines carrying the transgene of green fluorescent protein (GFP)-tagged type-1 NRG1 cDNA. The promoter of elongation-factor 1α gene drove ubiquitous expression of GFP-tagged NRG1 in the whole brain. As compared to control littermates, both heterozygous NRG1-Tg lines showed increased locomotor activity, a nonsignificant trend toward decreasing prepulse inhibition, and decreased context-dependent fear learning but exhibited normal levels of tone-dependent learning. In addition, social interaction scores in both Tg lines were reduced in an isolation-induced resident-intruder test. There were also phenotypic increases in a GABAergic marker (parvalbumin) as well as in myelination markers (myelin basic protein and 2',3'-cyclic nucleotide 3'-phosphodiesterase) in their frontal cortex, indicating the authenticity of NRG1 hyper-signaling, although there were marked decreases in tyrosine hydroxylase levels and dopamine content in the hippocampus. These findings suggest that aberrant hyper-signals of NRG1 also disrupt various cognitive and behavioral processes. Thus, neuropathological implication of hyper NRG1 signaling in psychiatric diseases should be evaluated with further experimentation.