European Journal of Neuroscience最新文献

Parkinson's disease (PD) is associated with alterations in both voluntary and reflexive eye movements; however, the characteristics of oculomotor variability across task contexts remain incompletely understood. This study investigated prosaccade, antisaccade and fixation parameters in 15 individuals with early- to midstage PD, assessed in the on-medication state and 15 age- and sex-matched neurologically healthy controls. Eye movements were recorded during structured saccadic tasks and during free-viewing of dynamic video stimuli using high-resolution binocular eye tracking. Compared with controls, participants with PD exhibited significantly higher prosaccade error rates and an increased peak velocity-to-amplitude ratio. Trial-to-trial variability, quantified using coefficients of variation, was consistently elevated in the PD group across multiple saccade parameters. During the video-viewing condition, changes in saccade metrics following video exposure were observed in the control group but not in the PD group, whereas fixation-based measures did not reliably differentiate groups. Together, these findings indicate that increased variability and reduced consistency of saccadic execution are prominent features of oculomotor control in PD without freezing of gait, particularly during reflexive saccade tasks. The results underscore the value of variability-based analyses for probing sensorimotor control in PD and motivate future work to examine their task dependence, longitudinal stability and relevance across disease stages.

Humans can adjust their walking patterns in response to both internal and external demands, a process referred to as locomotor adaptation. This process is crucial for walking in complex environments and is thought to be driven by sensory prediction errors. While the involvement of supraspinal structures is known, how the oscillatory coupling between the sensorimotor cortex and spinal motor neurons is involved in locomotor adaptation remains unclear. This study aimed to characterize the modulation of corticomuscular coherence (CMC), an index of this coupling, using a split-belt locomotor adaptation paradigm. We recorded electroencephalogram (EEG) and electromyogram (EMG) from the tibialis anterior muscle and calculated CMC in the alpha (8-12 Hz) and beta (12-32 Hz) bands. Results revealed that immediately following the application and removal of the perturbation, both alpha and beta CMC temporarily decreased compared to normal walking, suggesting a disruption of established corticomuscular coupling. However, during the adaptation process, alpha CMC in the slow leg's heel contact phase significantly increased toward normal walking levels. During de-adaptation, both alpha and beta CMC increased, and finally, CMC in all gait phases returned to normal walking levels. These results suggest that corticomuscular coupling was enhanced during the adaptation and de-adaptation processes. Thus, modulation of corticomuscular coupling may be associated with the adjustment of gait patterns to meet environmental demands. These findings will advance our understanding of neuromuscular control of gait and offer valuable insights for gait rehabilitation.

The acquisition of sexual experience leads female rats to return to the male more quickly after intromissions, receive intromissions at a faster rate, spend more time with the male during mating, and exhibit more proceptive behaviors during paced mating tests, suggesting heightened sexual motivation. Brain areas critical for sexual experience-enhanced paced mating behavior are unknown. Here, designer receptors exclusively activated by designer drugs (DREADDs) were used to test the hypothesis that silencing the medial amygdala (MeA) or ventromedial nucleus of the hypothalamus (VMH) across four paced mating tests would disrupt not only the display of paced mating behavior but also the enhancement of mating with sexual experience. Sexually naïve, ovariectomized rats received bilateral infusion into the MeA or VMH of a viral vector containing the gene for an inhibitory G-protein-coupled receptor (hM4Di) 3 weeks before behavioral testing. Rats were hormone primed with estradiol benzoate + progesterone and received either 1 mg/kg i.p. clozapine n-oxide (CNO) or vehicle 30 min before each of four 15-intromission tests of paced mating behavior. CNO given to rats lacking DREADD infusions did not exhibit disruptions to paced mating behavior. CNO-induced inhibition of the MeA altered paced mating behavior beginning with the first test, pointing to a role for the MeA in sensory processing of sexual stimulation. In contrast, inhibition of the VMH only led to changes in paced mating behavior on Tests 2-4, indicating that neural plasticity is induced in the VMH by sexual experience.

Event-related potentials (ERPs), and particularly change-elicited mismatch responses (MMRs), are valuable tools for assessing early speech processing and promising markers of dyslexia risk. Yet, their maturation during the preschool stage remains poorly characterized. We determined the typical elicitation of ERPs and MMRs to speech sounds at preschool age (4-5 years), their maturation from early childhood (28 months) to preschool age, and the impact of dyslexia risk on them. To this end, we recorded obligatory ERPs to a repeating pseudoword and MMRs to five deviances at 4-5 years and compared them with a previously reported follow-up at 28 months, in subgroups with versus without dyslexia risk in a large sample (n ~ 150). In the full sample, including both control and at-risk children, the 4- to 5-year obligatory ERPs showed a P1-N2 pattern, while the MMRs included a mismatch negativity (MMN) followed by a late discriminative negativity (LDN). From 28 months to 4-5 years, P1 amplitude increased and latency decreased, whereas the N2 amplitude increased. MMN and LDN amplitudes increased and LDN latency decreased with age, whereas a positive MMR reported at 28 months was no longer evident at 4-5 years. Crucially, at-risk children exhibited reduced MMN amplitudes at 4-5 years across deviants, suggesting deficient speech discrimination. Changes from 28 months to 4-5 years were similar in both subgroups. These findings establish a solid description of typical/atypical neural speech-sound processing during preschool years, serving as a reference for future studies including interventions or clinical groups.

Most treatments being developed to regain motor function following spinal cord injury (SCI) presuppose that brain motor functions remain intact. To examine this assumption, this study aims to analyze residual neurological functions during assisted robotic gait in individuals with SCI comparing blocks (gait × resting), time after SCI (acute × chronic), injury level (paraplegic × tetraplegic), and ASIA scale (ASIA C × D). The hemodynamic functions were analyzed using functional near-infrared spectroscopy (fNIRS) in 23 individuals (11 acute, 12 chronic; ASIA Impairment Scale grade C: 10, D: 13; paraplegia: 15, tetraplegia: 8) while performing an assisted robotic gait task (Lokomat). Brain areas analyzed included supplementary motor area (SMA), dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1), and primary somatosensory cortex (S1). Blocks (robotic gait × resting), acute × chronic, paraplegic × tetraplegic, and ASIA C × ASIA D groups were compared. For the block comparison, there was a significant difference in SMA and M1, with higher oxyhemoglobin values in the robotic gait task compared to resting. For the comparison between groups, there was a significant difference in M1, with higher oxyhemoglobin values in the chronic group compared to the acute group. The individuals with paraplegia exhibited greater activity in M1 than those with tetraplegia during the robotic gait task. These results demonstrate the plasticity and adaptability of brain motor cortex areas even during the chronic phase after SCI. The brain motor cortex activity during a walking motor task reinforces the importance of analyzing residual neurological function after SCI.

Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, a neuroendocrine system that regulates responses related to feeding, reproduction, and aggression, among other homeostatic functions. Stressors significantly impact gene expression along the HPA axis and in hypothalamic nuclei that drive it, including the paraventricular nucleus (PVN). To identify genetic regulators of stress responses in the PVN, adult mice underwent 2 h of multi-modal stress before gene expression profiles were analyzed using bulk RNA sequencing. A transcription factor zinc finger and BTB domain containing 16 (Zbtb16), also known as PLZF, was identified as a stress responsive, glucocorticoid receptor (GR) target in the PVN. Zbtb16 mRNA expression was increased by two-fold in male and female mice within 2 h of restraint stress or injection of a synthetic glucocorticoid, dexamethasone (DEX). Immunohistochemistry (IHC) confirmed Zbtb16 protein expression and localization in the PVN following 20 min of restraint stress and 4 h of recovery. Cellular analyses revealed that Zbtb16 was highly expressed in CRH neurons in the PVN, neurons routinely activated post-stress as indicated by colocalization with c-FOS. Adult mice were also exposed to an immune stress by injection of tumor necrosis factor alpha (TNFα) to assess Zbtb16 regulation. Expanded analyses indicated that the cell specificity of Zbtb16 expression was region-specific, colocalizing with CRH neurons in the mid-PVN but more in astrocytes surrounding the PVN. These findings identify Zbtb16 as a glucocorticoid- and cytokine-inducible transcriptional regulator with region- and cell type-specific roles in PVN stress circuitry.

Freezing of gait (FoG) and falls are among the most disabling symptoms in late-stage Parkinson's disease (PD). While right-lateralised thalamic cholinergic denervation has been linked to FoG and gait impairment, it is unclear whether similar asymmetry exists within the cortically-projecting cholinergic basal forebrain (cBF), particularly the nucleus basalis of Meynert (Ch4). In this cross-sectional study, we assessed structural MRI in 136 nondemented people with PD, stratified into three groups: FoG (n = 18), fallers without FoG (n = 31) and nonfallers without FoG (n = 87). Subregional cBF volumes were quantified using volumetry, normalised by total intracranial volume and compared across groups. Mixed ANOVAs revealed significantly reduced Ch4 and Ch4p volumes in the FoG group compared to both other groups, with right-lateralised Ch4p atrophy observed specifically in FoG. After adjusting for disease severity, sex, levodopa equivalent dose (LEDD), and most affected side, the FoG group continued to show significantly reduced volumes in only the right Ch4p. A mediation model indicated that global cognitive performance (MoCA) did not significantly mediate the association between Ch4p volume and FoG status, suggesting that Ch4p degeneration may contribute to FoG through mechanisms not captured by global cognition alone. Overall, the findings support a right-hemisphere cholinergic vulnerability in FoG, implicating Ch4p degeneration in networks relevant to both gait regulation and attentional-visuospatial function. Future longitudinal studies are needed to determine whether this lateralised structural vulnerability predicts progression to FoG or cognitive decline in PD.

Whereas the circumstances under which episodic memory benefits from Virtual Reality (VR)-based encoding remain elusive, preliminary findings suggest that the contributions of the underlying retrieval processes might depend on the encoding modality. Previous research indicates that engrams obtained from VR conditions elicit enhanced recollection alongside attenuated familiarity. However, it remains unclear whether this pattern depends on the congruence of the encoding and retrieval contexts. Consequently, this study examined potential context-transfer effects on the electrophysiological correlates of familiarity and recollection after VR-based and PC-based encoding. A source memory paradigm was employed to test the retrieval of objects and their encoding context, i.e., item and source memory under VR conditions. The electrophysiological results indicated attenuated familiarity of PC-based engrams reflected in the frontal old/new effect (FN400), yet the same held true for VR-based engrams. Moreover, a strong old/new effect in the late positive component (LPC) linked to recollection was evident under both conditions. In contrast, the late posterior negativity (LPN), linked to the search for and reactivation of contextual details during retrieval, was observed under neither condition. In summary, the present results indicated comparable contributions of familiarity and recollection to retrieval, independent of the encoding modality, when retrieval occurred under VR conditions. While effects on engrams retrieved without their correct source might, to some degree, depend on context-transfer effects, familiarity was attenuated across encoding modalities. Consequently, the present results demonstrate that disparities between VR- and PC-engrams depend on the combination of encoding and retrieval modalities and extend beyond context-transfer effects.

Poststroke aphasia significantly impacts the quality of life in older adults, yet the underlying neural mechanisms linking macro-scale network hierarchy and micro-scale molecular architecture remain unclear. This study investigated alterations of the principal functional connectivity gradient and their transcriptomic underpinnings in older adults with poststroke aphasia. We recruited 27 patients with aphasia and 29 age-matched healthy controls. Resting-state fMRI data were analyzed using diffusion map embedding to characterize the principal functional connectivity gradient. Patients exhibited a compressed gradient range, characterized by diminished differentiation in unimodal networks (visual and somatomotor) and disordered integration in multimodal networks, including the ventral attention network and the default mode network. These gradient alterations were significantly correlated with language deficits. Furthermore, partial least squares regression revealed that the spatial pattern of gradient changes was associated with normative gene expression profiles related to synaptic transmission, trans-synaptic signaling, and calcium ion binding. Machine learning models incorporating gradient features and lesion volume successfully predicted individual differences in language performance. These findings suggest that poststroke aphasia involves a disruption of the cortical functional hierarchy that is constrained by specific molecular architectures, providing novel insights into the neurobiological mechanisms of language recovery and potential targets for precision rehabilitation in aging populations.

Parkinson's disease (PD) is a neurodegenerative syndrome with diverse biological drivers, where gait and balance dysfunction remain among the most disabling and least understood symptoms. Bassoon (BSN), a presynaptic active-zone organizer, has been implicated in various parkinsonian disorders. Here, we report the impact of BSN mutations on motor symptoms, especially gait-related symptoms, in PD patients. Our study included 110 patients carrying BSN mutations in a cohort of 668 South Asian early-onset PD (age of onset < 50 years). Clinical motor features were compared between variant carriers and noncarriers. Computational tools (CADD, PolyPhen-2, I-Mutant2.0 and ConSurf) predicted deleteriousness of individual mutations, whereas GeneMANIA and STRING speculated Bassoon's functional interactions. Subjects carrying BSN variants exhibited significantly increased burden of motor-related symptoms (p = 0.036). Freezing of gait (FOG) and shuffling gait (SG) were significantly more prevalent in BSN mutation carriers (p = 0.03). Presence of BSN mutation correlated with an increased disease stage, an effect driven by FOG and SG (p = 0.012). Rare BSN mutations (MAF < 0.1%) clustered in the Bassoon C-terminal region (aa 3500-3800), at a threefold frequency than expected (p < 0.01), implying a hotspot. In silico analysis identified seven likely pathogenic variants (P171L, A852T, P988A, R1015H, R2561H, R3400W and L3561P). Predictive analyses implicated BSN in axonal transport, presynaptic proteostasis and neurotransmitter release in dopaminergic/cholinergic neurons. Our findings put forth BSN mutations as a potential genetic risk factor for PD-related motor and gait dysfunction, warranting further research in this respect.