European Journal of Neuroscience最新文献

The continuity illusion occurs when a sound is perceived as continuous through noise-filled interruptions and has been indexed neurophysiologically as reduced auditory theta band (4-8 Hz) power and phase-locking at the interruption boundaries. Here, we examined the behavioural and neurophysiological differences between musicians (n = 16) and nonmusicians (n = 16) as they listened to trisyllabic words and classical music with noise interruptions. Our aim was to assess two competing hypotheses: (H₁) because of their enhanced ability to detect acoustic gaps, musicians are less likely to perceive continuity and will therefore exhibit increased theta power/phase-locking at interruption boundaries compared to nonmusicians. Alternatively, (H₂) musicians are more likely to perceive continuity through an enhanced ability to utilize contextual cues to fill in missing information. This top-down influence should be demonstrated by reduced theta power/phase-locking in musicians. On each trial, participants reported whether a noise-interrupted music or speech stimulus sounded continuous or interrupted. Behaviorally, musicians and nonmusicians had similar rates of perceived continuity for music and speech, except musicians exhibited significantly greater continuity to speech at the shortest noise interruption. The oscillatory results demonstrated that relative to nonmusicians, musicians had weaker theta phase-locking to the interruption boundaries in both music and speech, supporting H₂. Musicians also exhibited enhanced alpha (8-13 Hz) and beta (14-30 Hz) power for both music and speech relative to nonmusicians, possibly reflecting inhibitory processes. We conclude that musicians exhibit enhanced auditory-motor inhibition to noise interruptions in both music and speech and infer this is due to their enhanced ability to utilize contextual cues.

Synapse elimination during development is crucial for refining neural circuits by removing excess synapses formed around birth. In the neonatal cerebellum, Purkinje cells (PCs) are initially innervated by multiple climbing fibers (CFs) with similar synaptic strengths. During subsequent postnatal development, a single CF is strengthened and retained, while the other CFs are eliminated. Here, our PC-specific RNAi knockdown (KD) screening revealed that fibronectin type III domain containing 3B (FNDC3B), an endoplasmic reticulum protein, was involved in CF synapse elimination from around postnatal day 9 (P9) in mice. We showed that FNDC3B mRNA was expressed in PCs during CF synapse elimination. In PC-selective FNDC3B conditional knockout (FNDC3B-cKO) mice, CF synapse elimination from P10 was impaired, and the extension of CFs along PC dendrites was reduced at P21. However, these phenotypes were recovered by P40. In contrast, parallel fiber-mediated excitatory synaptic inputs and inhibitory synaptic inputs to PCs were not affected in FNDC3B-cKO mice. These results suggest that FNDC3B facilitates CF synapse elimination during postnatal development, highlighting a new role of FNDC3B in the developing brain.

Sleep supports memory formation by neurophysiological mechanisms that are yet to be fully uncovered. We investigated the contribution of the direct coupling of neurons via electrical synapses (gap junctions). The administration of mefloquine (250 mg p.o. vs. placebo), an antimalarial, which blocks electrical synapses, to healthy young men before nocturnal sleep impaired the retention of word pairs learned before drug administration and disrupted the coupling of sleep spindles to EEG slow oscillations. In control experiments, in which participants received mefloquine before a consolidation interval of nocturnal wakefulness or after rather than before sleep, word-pair memory retention was not affected by the drug, suggesting that electrical synapses specifically support the sleep-dependent retention of verbal declarative memory. Irrespective of sleep, mefloquine enhanced the retention of sensorimotor memory assessed with a finger sequence tapping task. In supplemental experiments in rats, mefloquine administered i.p. at escalating doses of 20 and 40 mg/kg did not alter hippocampal sharp-wave/ripple activity, a prominent mechanism of hippocampal memory replay. While mefloquine effects beyond gap junctions in the present experiments cannot be fully excluded, we conclude that electrical coupling enhances the oscillatory coordination between sleep spindles and slow oscillations and, thereby, supports systems memory consolidation.

In a rubber hand illusion, participants experience illusory ownership (embodiment) of a seen fake hand when it is stroked synchronously with their unseen real hand. A recent investigation demonstrated that participants exhibited significantly faster reaction times when instructed to lift their index finger immediately after observing the index finger movement of an embodied (i.e., rubber hand illusion) versus a nonembodied (i.e., nonrubber hand illusion) fake hand. The current study examined whether this facilitation in reaction times arises from enhanced visual processing of the observed movement or from motor facilitation driven by a visuo-proprioceptive conflict between the embodied fake hand and the participant's hand. Two experiments were conducted, in which participants were required to lift their index finger in response to a neutral auditory stimulus following illusion induction. To isolate the contribution of visual processing, the visual stimulus (i.e., fake finger movement) was presented before the auditory cue with different stimulus onset asynchronies (500, 1000, or 1500 ms). In Experiment 1, the fake finger remained elevated until the participant initiated their movement, whereas it lowered soon in Experiment 2. The results revealed that the reaction time advantage in the rubber hand illusion condition was independent of stimulus onset asynchronies and emerged exclusively in Experiment 1. No significant differences were observed in peak velocity and acceleration of finger movement. These findings suggest that the ownership-dependent facilitation of reaction times is not due to visual processing alone but rather to motor facilitation mechanisms driven by visuo-proprioceptive discrepancy at the termination of the fake finger movement.

Others have shown that dopamine receptors regulate the migration of GABAergic cortical interneurons (cINs) to the developing cortex. Given the strong expression of Drd1, the gene encoding the D1 dopamine receptor (D1R) in the developing cortex, we examined here the role of D1R in the cortical migration of interneurons born in the medial ganglionic eminence (MGE). Embryos of transgenic mice expressing cytoplasmic GFP under the control of the Drd1 promoter exhibited strong GFP expression in cells located in the deep cortical layers, including the subplate, and in the marginal zone. In co-culture experiments aimed at characterizing the effect of selective Drd1 ablation either in interneurons or in cortical plate cells on the migratory behavior of interneurons, we identified a prominent pro-migratory non-cell autonomous effect of Drd1 ablation in the cortical substrate. To assess whether Drd1 ablation in cortical cells could influence the final interneuron distribution in vivo, we analyzed the cortical distribution of parvalbumin and somatostatin positive interneurons in the cortex of Drd1-CKO (Drd1-/- cortical cells, Drd1+/+ interneurons) mice. Wild type parvalbumin and somatostatin interneurons exhibited slight but significant density changes and alterations of latero-dorsal distribution compatible with the pro-migratory effect of Drd1-/- cortical cells. In Drd1-KO animals (Drd1-/- cortical cells and Drd1-/- interneurons), the distribution alterations of parvalbumin and somatostatin interneurons were reminiscent of those in Drd1-CKO mutants. We thus propose that D1R regulates in the cortex the motility and distribution of MGE-derived cINs by preponderant non-cell-autonomous mechanism.

Uncertainty is a key contributor to decision making, and humans show inconsistent attitudes towards it. Although excessive uncertainty-avoidance or uncertainty-seeking are hallmark symptoms of several mental conditions, the neural mechanism underlying uncertainty seeking and avoidance remains unclear. Here, we probed whether changes in pupil-linked arousal are indicative of uncertainty avoidance in humans. Investigating baseline pupil size to capture endogenous fluctuations across two experiments (N₁ = 24, N₂ = 21), we found that pretrial pupillary responses (as early as 700 ms prior to the onset of a trial) were closely related to uncertainty attitudes during multiarmed bandit tasks. Although increased baseline pupil size signalled avoidance in uncertainty-related decisions, it did not foreshadow value processing per se. The specificity of our results suggests that uncertainty processing is dynamic and depends on (potentially noradrenergic) endogenous pupil fluctuations.

Gait impairments impact independence and quality of life of persons with Parkinson's disease (PD). The application of external and internal cueing strategies can improve gait, but not every person benefits equally from the same strategy. It remains unclear (i) which patient characteristics mediate cueing efficacy, (ii) how cueing efficacy changes over time, (iii) which patient characteristics are associated with long-term compliance, and (iv) what the neural correlates of cueing are. The UNITE-PD study is a collaboration between the Radboud University Medical Center (NLD), KU Leuven (BEL), Tel Aviv Sourasky Medical Center (ISR), and IRCCS Policlinico San Martino (ITA). The study consists of a joint prospective cohort project and four site-specific projects. We here describe the joint project, with the site-specific projects included as supplementary materials. All participants undergo a baseline assessment, consisting of extensive clinical testing and an objective gait assessment with and without external and internal cueing. Responders and non-responders to the strategy will be followed for 6 months. Responders will be instructed to apply the effective cueing strategies, as much as possible in daily life using a mobile cueing application which tracks compliance. At 6 months post-baseline, responders and non-responders return to the lab, during which the baseline protocol will be repeated to quantify the change in efficacy of the cueing strategies over time. The UNITE-PD study will identify the relationship between patient characteristics, cueing efficacy, compliance, and the underlying mechanisms of cueing. This knowledge will help refine personalized rehabilitation and identify new avenues for neuroscientific inquiry in this domain.

Previous studies of verbal working memory (WM) have reported inconsistent changes in alpha power during retention, with both increases and decreases observed. We asked whether these discrepancies arise from how stimuli are presented. Thirty adults memorized seven digits presented in four modes: Simultaneous (all digits for 2800 ms) or sequential presentations at Fast (400 ms per digit), Slow (1000 ms per digit), and Fast + delay (400 ms per digit plus a 600-ms free time in between). We analyzed EEG during encoding and a 6-s retention period in theta (4–7 Hz), alpha (8–13 Hz), and beta (18–24 Hz) frequency bands. Encoding produced parametric load-related theta increase and beta decrease, possibly reflecting growing executive control demands and motor program formation, respectively. Alpha power did not scale with load during encoding. Single trial models linked stronger encoding theta and deeper alpha suppression to better recall, whereas retention power did not predict accuracy. During retention, theta and beta were unaffected by presentation mode. Alpha power did not differ significantly when all sequential modes were grouped together compared to the simultaneous mode. However, the Fast + delay mode uniquely showed below-baseline alpha in the first half of the retention. Our findings suggest that alpha dynamics are sensitive to the temporal structure of encoding and retention periods, particularly the presence or absence of free intervals between stimulus presentations. We propose that alpha modulation during WM retention may reflect processes beyond the simple gating of irrelevant sensory information.