Brain Sciences最新文献

Objectives: The present study aimed to explore psychiatrists' perceptions of duloxetine in routine clinical practice, focusing on its efficacy, tolerability, and treatment adherence in major depressive disorder (MDD) and generalized anxiety disorder (GAD). Methods: A structured questionnaire was administered to 97 psychiatrists from different regions of Spain. The survey covered demographic and professional data, prescription frequency, perceived clinical efficacy, tolerability, dosing patterns, and factors influencing adherence. Results: Overall, duloxetine was perceived as an effective treatment for both MDD and GAD, particularly in patients with somatic symptoms or comorbid anxiety. Tolerability was also positively rated, with nausea and fatigue identified as the adverse effects most commonly associated with reduced adherence. In addition, patient education and close follow-up were identified as the most effective strategies to improve adherence, whereas digital tools were considered promising but underused. Compared with other antidepressants, duloxetine was viewed as having a favorable balance between efficacy and tolerability, with similar or slightly higher adherence rates. Conclusions: These findings reflect a positive clinical appraisal of duloxetine among psychiatrists, highlighting its role as a versatile therapeutic option for affective and anxiety disorders, within the context of routine clinical practice in Spain, provided that appropriate adherence-support strategies are implemented.

Background/Objectives: Primary progressive aphasia (PPA) is a clinical syndrome associated with gradual language impairment caused by neurodegenerative disease. While people with post-stroke aphasia often depend on visual and prosodic cues to facilitate language, we hypothesized that people with PPA may have difficulty using such cues due to degeneration in the right hemisphere (albeit less than in the left hemisphere) in PPA. Methods: Eighty-eight outpatients diagnosed with PPA received the Hopkins Auditory Comprehension with Context Assessment (HACCA), a recently developed instrument that systematically titrates both acoustic (prosody) and visual (speaker image) cues in a four-item forced-choice sentence picture matching paradigm assessing comprehension. Patients were grouped based on the effects of cues on accuracy and were examined both by the PPA variant and individually. Results: There was a significant difference between performance classifications across the three cueing conditions as a function of PPA variant (p = 0.014). When individuals with distinct complementary profiles of performance across conditions were examined separately, a small number with logopenic PPA uniquely benefitted from the inclusion of video, while certain patients performed more poorly given any additional cues. HACCA performance across cueing conditions had a strong positive association with other concurrent measures of communication and cognition. Conclusions: Individual patterns of response to prosodic and visual cues provide important insights valuable in refining therapeutic approaches that target the retention of function and support a more robust understanding of the individual variability among patients with this uncommon neurodegenerative syndrome.

Neural oscillations are fundamental to the integration of sensory, affective, and cognitive processes that contribute to pain perception. Transcranial alternating current stimulation (tACS) provides a valuable tool for investigating and modulating these oscillatory dynamics. In this review, we examine the effects of tACS on pain perception and pain-related oscillations in both healthy participants and individuals with chronic pain, highlighting methodological variability and mechanistic uncertainties that may contribute to mixed findings. We identified 14 studies, including 9 studies of experimental pain in healthy individuals and 5 of clinical pain disorders, comparing tACS to sham. Somatosensory alpha was the most frequently targeted oscillatory feature. Results varied considerably. Several studies reported reductions in pain, increases in alpha power, or changes in sensorimotor and prefrontal connectivity, but others showed no meaningful neural or behavioral effects. Out of the 14 studies, 6 demonstrated analgesic benefits and 2 showed improvements only under specific conditions or within subgroups, for a total of 8/14 studies with positive findings. Possible sources of heterogeneity include variation in stimulation duration, electrode montage, frequency alignment with individual rhythms, contextual state, and anatomical and neurophysiological differences across individuals. Pre-registered studies with sufficient power are needed to replicate effects within the most promising intervention protocols to establish a foundation in the field. We also recommend inclusion of brain imaging or electrophysiological recordings to verify whether stimulation effectively modulates the targeted neural oscillations. Finally, recent methodological advances, including phase-specific tACS, amplitude-modulated tACS, and individualized electric-field modeling, offer new opportunities to enhance mechanistic precision and clinical applicability. We argue that by integrating these approaches, future research can move beyond fixed, one-size-fits-all protocols toward personalized, state-dependent, closed-loop tACS approaches. Exploring these frontiers will transform tACS from an exploratory tool into a reliable intervention for pain.

The regulation of sensory processing by centralized neuromodulatory systems can alter behavioral responses to social cues. Neuromodulatory systems such as the serotonergic neurons in the dorsal raphé nucleus (DRN) show heterogenous responses to different types of sensory stimuli or to stimulus qualities such as reward, valence, or salience. Sensory neuromodulation could therefore be related to a broader quality of the behavioral context or to specific types of social cues. We assessed this issue by presenting male mice with either playback of female vocal signals associated with defensive aggression (squeaks) or silence, and the presence or absence of a female. Activity in regions of the DRN that project to the auditory midbrain was assessed through co-labeling with antibodies to the serotonin synthetic enzyme tryptophan hydroxylase (TPH) and the immediate early gene product c-Fos. Female presence or absence had the largest effect, decreasing the co-localization of TPH and c-Fos, while the playback of squeaks had effects that were condition-dependent, increasing co-label only when females were absent. Squeak playback further decreased the correlation in the numbers of co-labeled neurons between two dorsal subdivisions of the DRN, the DRD and DRL. These results are inconsistent with an auditory-exclusive feedback loop. Instead, cues associated with female presence heavily influence raphé activity, with squeaks playing a modifying and context-dependent role. Because the elevation of serotonin in the IC causes males to become more responsive to female squeaks, these findings suggest that a nuanced interaction of positive and negative cues during social interaction may fine-tune male responses to the vocalization of social partners, in part through the serotonergic system.

Background: this paper reports an investigation into the cognitive and emotional states of adolescents while learning from an LLM. It seeks to address a relative dearth in empirical evidence which might otherwise facilitate informed decisions being made by curriculum designers, school leaders and policy makers regarding the use of Generative AI, amidst the wider discourse about the effectiveness of AI in teaching and learning.

Methods: in this paper, we analyze electrodermal activity (EDA) in the context of students' scholastic engagement using LLMs in comparison to curated texts. In our 27-min-long experiment, we recorded the EDA of participants learning from both learning methods, for 8 min each. A quiz was also conducted to assess the effectiveness of the learning method. We collected 23 samples of EDA from the experiment, and 42 samples of quiz results.

Results: we have found that learning with an LLM results in greater Skin Conductance Response (p = 0.09404), which is linked to more positive emotional valence, and lower Skin Conductance Level (p = 0.09473), which is linked to lower cognitive load, compared to curated texts. We also discovered that learning with an LLM correlates to a higher quiz result (p = 0.02053). While this suggests that learning and absorbing information with an LLM could be more effective than curated texts, results from self-reported data indicate that there are few perceived differences between the effectiveness of LLM and curated texts.

Conclusions: this exploratory and preliminary study revealed empirical insights between LLM usage and learning effectiveness in situ via physiological indicators, in contrast to prior work that has adopted post hoc frames over the medium- to long-term.

Parkinson's disease (PD) is characterized by progressive degeneration of the nigrostriatal dopaminergic system and α-synuclein (α-syn) pathology, with disease progression driven by convergent mechanisms including neuroinflammation, mitochondrial injury, oxidative stress, and regulated cell-death programs such as ferroptosis. Fibroblast growth factors (FGFs) and fibroblast growth factor receptors (FGFRs) constitute a key signaling system in the central nervous system, influencing not only neuronal survival and glial states but also intersecting with networks governing redox homeostasis and iron metabolism. Accumulating evidence indicates that, beyond classical neurotrophic actions, FGF-FGFR signaling can modulate mitochondrial quality control, glial inflammatory activation, and lipid peroxidation-related processes, thereby reshaping cellular susceptibility to ferroptotic injury. This review summarizes current advances in understanding FGF signaling networks in Parkinson's disease, synthesizes their potential mechanistic links to the interplay among neuroinflammation, mitochondrial dysfunction, and redox imbalance as well as to ferroptosis regulation, and discusses the experimental basis and translational challenges of targeting the FGF pathway as a disease-modifying therapeutic strategy.

Background/Objectives: From birth, infants learn how to interact with the world through exploration. It has been proposed that this early learning phase is driven by motor babbling: the spontaneous generation of exploratory movements that are progressively consolidated through associative mechanisms. This process leads to the acquisition of a repertoire of hand movements such as single- or multi-finger flexion, extension, touching, and pushing. Later, in a second phase, some of these movements (e.g., those that happen to enable access to biologically salient stimuli, such as grasping food) are further reinforced and consolidated through rewards obtained from the environment. However, the neural mechanisms underlying these processes remain unclear. Here, we used a fully neuroanatomically and neurophysiologically constrained neural network model to investigate the brain correlates of these processes. Methods: The model consists of six neural maps simulating six human brain areas, including three pre-central (motor-related) and three post-central (sensory-related) regions. Each map is composed of excitatory and inhibitory spiking neurons, with biologically constrained within- and between-area connectivity forming recurrent circuits. Hand action execution and corresponding haptic perception are simulated simply as activity in primary motor and somatosensory model areas, respectively. During an initial "exploratory" phase, the network learned, via Hebbian mechanisms, associations-as emerging distributed cell assembly (CA) circuits-linking "motor" to corresponding "haptic feedback" patterns. As a result of this initial training, the model began to exhibit spontaneous ignitions of these CA circuits, an emergent phenomenon taken to represent internally generated, non-stimulus-driven attempts at hand action exploitation. In a second phase, a global reward signal, simulating dopamine-mediated reward encoding, was applied to only a subset of "successful" actions upon their noise-driven ignition. Results: During the first exploratory phase, the neural architecture autonomously developed "action-perception" circuits corresponding to multiple possible hand actions. During the subsequent exploitation phase, positively reinforced circuits increased in size and, consequently, in frequency of spontaneous ignition, when compared to non-rewarded "actions". Conclusions: These results provide a mechanistic account, at the cortical-circuit level, of the early acquisition of hand actions, of their subsequent consolidation, and of the spontaneous transition of an agent's behavior from exploration to reward-seeking, as typically observed in humans and animals during development.

Background/Objectives: Motor imagery (MI) is the mental practice of motor actions with temporal dynamics and neural features in common with motor execution (ME). Although MI can improve motor performance, it remains unclear how closely performance-related signatures of MI resemble those of ME during learning, particularly in tasks with intrinsic variability. This study investigated similarities and differences between MI and ME during a probabilistic sequence-learning task. Methods: Participants performed a finger-tapping serial reaction time task in either a motor execution (ME; n = 10) or motor imagery (MI; n = 10) condition. The task consisted of 750 auditory stimuli mapped to right-hand finger movements and generated by a probabilistic sequence with deterministic and variable events. Reaction times were analyzed using ANOVA designs to assess the effects of Group, Block, Event Type, and the Last Variable event. Results: The MI group showed a significant reduction in reaction times across blocks (p < 0.001), indicating learning-related performance improvement, whereas no block-wise improvement was observed in the ME group. Both groups were sensitive to the probabilistic structure of the sequence, with reaction times differing across event types. A significant Group × Event interaction (p < 0.01) indicated distinct performance signatures for MI and ME. In both groups, reaction times were modulated by the last variable event. Conclusions: Motor imagery supported learning in a probabilistic sequence task but was influenced by factors distinct from those governing motor execution, suggesting partially different underlying mechanisms.

Background: Proton pump inhibitors (PPIs) are commonly used to manage acid-related gastrointestinal conditions. Nevertheless, growing attention has been paid to their long-term safety, especially their possible link to dementia and Alzheimer's disease (AD). Prior research has yielded inconsistent findings, underscoring the need for a comprehensive and current evaluation.

Methods: A systematic search was conducted across PubMed, Embase (Ovid), and the Cochrane Library to identify relevant publications up to May 28, 2025, without language restrictions. Two investigators independently extracted study information and evaluated methodological quality as well as potential sources of bias. Eligible studies were observational in design and investigated the association between proton pump inhibitor (PPI) exposure and the risk of developing dementia compared with non-use. For the quantitative synthesis, pooled risk ratios (RRs) and corresponding confidence intervals were generated using a random-effects approach.

Study results: Eighteen studies, encompassing more than 6.3 million participants, met the inclusion criteria. The pooled estimate showed no statistically significant association between PPI use and overall dementia risk (RR = 1.14, 95% CI 0.98-1.33; I² = 99%). However, significant heterogeneity and variable risk of bias-particularly due to confounding, exposure misclassification, and immortal time bias-limit certainty in these findings. Subgroup analyses revealed significantly elevated risks among individuals aged ≥65 years (RR = 1.21, 95% CI 1.01-1.46) and in studies from Asia (RR = 1.31, 95% CI 1.12-1.52) and Europe (RR = 1.32, 95% CI 1.10-1.59), suggesting possible population- or context-specific vulnerability.

Conclusions: Our findings reveal a lack of consistent evidence supporting a link between PPI use and dementia risk, primarily due to significant heterogeneity among existing studies. While no robust overall association was demonstrated, significant subgroup signals in older adults and specific regions suggest that clinical uncertainty remains. Rather than indicating a direct causal risk, these results underscore the importance of prescribing stewardship. Clinicians should focus on appropriate prescribing, ensuring long-term PPI therapy is reserved for patients with a clear therapeutic justification and utilized for the shortest effective duration.

Background: Stroke is a leading cause of long-term disability worldwide. Non-invasive or transcutaneous auricular vagus nerve stimulation (taVNS) shows promise in promoting neuroplasticity and supporting motor recovery. There are currently no validated biomarkers of taVNS. High-density diffuse optical tomography (HD-DOT) is a portable neuroimaging technology that uses near-infrared light to map cortical activity via the quantification of changes in blood oxygenation. The aim of this study was to determine whether HD-DOT could detect motor task-related activity with concurrent taVNS. Methods: Thirty-one healthy participants completed right and left finger tapping tasks with concurrent sham (earlobe) and then active (tragus) taVNS in a within-subject block design. HD-DOT was recorded across the bilateral sensorimotor cortex using 36 sources and 48 detectors (1728 channels). Cortical reconstructions were parcellated and block-averaged task-related oxygenated and deoxygenated haemoglobin changes were compared between sham and active taVNS conditions. Results: In a group-level analysis, appropriate lateralised task-related haemodynamic responses were seen in the contralateral sensorimotor regions, demonstrating the validity of HD-DOT. Between-group comparisons showed no significant change in task-related activation during right finger tapping tasks under active vs. sham taVNS conditions. A non-significant redistribution of task-related activity to the right motor cortex was seen with left finger tapping under active taVNS compared to sham taVNS. Conclusions: Simultaneous recording of neural responses to taVNS during motor activity was feasible and well tolerated. Reliable task-related activation was recordable. Future studies of whole brain HD-DOT in people with stroke will help evaluate its potential as a biomarker in taVNS.