The availability of efficacious pharmacotherapies for the treatment of cocaine use disorders remains a significant unmet societal need. Cocaine exerts its psychoactive effects primarily by inhibiting presynaptic reuptake of monoamine neurotransmitters, including serotonin (5-HT). There are at least 14 different 5-HT receptor subtypes in the brain, and prior studies have shown that the 5-HT 7 receptor subtype plays a role in learning and memory, neural plasticity, impulsivity, alcohol intake, and some behavioral responses to psychostimulants. In this study, we sought to determine the effects of the selective 5-HT 7 antagonist SB-656104A on cocaine self-administration under conditions of increasing behavioral demand using the progressive ratio paradigm. Male rats were trained to self-administer cocaine at a dose of 0.75 mg/kg/infusion. Following acquisition and stabilization of operant responding on a fixed-ratio schedule and subsequent transition to and stabilization under progressive ratio conditions, animals were treated with vehicle or one of three doses of SB-656104A (3, 10, or 20 mg/kg) prior to additional progressive ratio sessions. None of the doses of SB-656104A had any effect on breakpoints for cocaine intake or time to reach breakpoint. These data indicate that blockade of 5-HT 7 receptors with SB-656104A does not alter cocaine intake under conditions of increased behavioral demand. Nonetheless, further studies with other 5-HT 7 ligands should be pursued.

The interaction effects of hypertension and aging on brain network in spontaneously hypertensive rats: A resting-state functional magnetic resonance imaging study.

Ovarian sex steroid hormones play a critical role in regulating fertility. In addition, these hormones influence behavior and mood across the lifespan in females. Converging evidence from rodent studies and human neuroimaging shows that ovarian hormones dynamically regulate neuronal excitability, synaptic efficacy, and structural remodeling across menstrual/estrous cycles, puberty, and reproductive aging. Estrogen and progesterone reorganize network dynamics and gate plasticity eligibility rather than uniformly scaling synaptic strength, with additional contributions from glia, the extracellular matrix, and neurosteroid signaling. Here we synthesize recent cross-scale advances that link structural and functional changes to cellular and circuit mechanisms, and relate these dynamics to female-biased vulnerabilities in affect, cognition, and social behavior.

Adverse childhood experiences (ACEs) are associated with negative consequences for physical and mental health. ACEs are defined as harmful experiences from conception to age 18. They generate chronic toxic stress when exposed to emotional or sexual abuse or a dysfunctional home. ACEs produce "programming" on brain plasticity with immunoneuroendocrinological, cerebral, and epigenetic changes. The result is suboptimal development of physical, mental, and emotional abilities. This "programming" can be mitigated by resilience, family and social support. When faced with new stressors, psychological and physiological dysregulation will occur, exposing the individual to disease. Between the ages of 0 and 17, 55.9% have had 1 ACE, and 30.6% have had ≥2 ACEs. The consequences are aggression, drug addiction, obesity, asthma, depression/anxiety, decreased resilience, juvenile recidivism, and suicide. Pediatricians are the ones who can detect, prevent, and mitigate ACEs.

Prolonged screen exposure in early childhood is linked to developmental challenges, particularly in executive functions (EF), which are critical for child adjustment. While infancy is recognized as a sensitive period of heightened brain plasticity and susceptibility to environmental influences, research on screen exposure during this time is limited, with most studies focusing on children over 2 years. Policymakers, recognizing the plasticity of the infant brain, have issued strict guidelines advocating for the complete avoidance of screen exposure for children under two; yet, approximately 75% of children in this age group exceed these recommendations. This underscores the need to better understand individual differences in screen-related risks to develop empirically informed, nuanced guidelines. Surprisingly, despite temperament being a key characteristic in infancy, shaping how infants respond to environmental inputs, its role in moderating the impact of screen exposure on regulatory development has not been studied. This study addresses these gaps by exploring temperamental negative emotionality (TNE) as a moderator between infant screen exposure and later EF difficulties. Eighty infants participated (57.5% males, all White, 73.3% monthly household income >3,400 U.S. dollars); TNE was assessed at 4 months, screen exposure at 10 months, and EF at 4 and 5.5 years. Results indicate that higher screen exposure in infancy predicts later EF difficulties but only for infants with average/high TNE. Our findings provide initial evidence suggesting the potential need to consider temperament-related individual differences when developing more nuanced, individualized guidelines for infant screen exposure. Such guidelines may enhance adherence and mitigate screen-related risks. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Gene expression levels of brain-derived neurotrophic factor in the olfactory system of masu salmon Oncorhynchus masou during both seaward and homeward migrations.

Metaphors have long played multiple roles in conceptualizing the mind and brain, guiding the development and refinement of theoretical models and empirical questions. Early analogies(comparing the brain to hydraulic systems, telephone exchanges, factories, or libraries) offered shortcuts to understanding aspects of cognition, memory, and brain dynamics. From theoretical frameworks, metaphors like the mind as a computer evolved into central scientific metaphors, shaping core theoretical frameworks, inspiring predictions, and informing research methodologies. As such, metaphors play a key role in guiding scientific inquiries. Building on that premise, we propose music as a scientific metaphor for understanding multiple brain dynamics and cognitive functions. Unlike metaphors focusing on static components or linear flows, music emphasizes continuous adaptation, context-dependence, and cultural embedding, and presents a model for simultaneous engagement with multiple layers of meaning. Integrating analytical techniques from music theory and experiential insights from performance and listening, we can deepen our understanding of mind and brain dynamics and provide fresh epistemological pathways for interdisciplinary research. Music has a hierarchical structure, temporal complexity, and capacity to integrate multiple processes that parallel key features of the brain's architecture and cognitive functions. Drawing from research on neural oscillations, plasticity, predictive coding, and emotional processing, we illustrate how the musical paradigm can capture the rich entanglement of mind and brain, from large-scale brain dynamics and developmental trajectories to the emergence of consciousness and the interplay of affective states.

The extracellular matrix as a dynamic regulator of brain function and plasticity.

Activity-dependent plasticity, mediated by mechanisms such as long-term potentiation (LTP), underlies learning and memory. Intermittent theta-burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation (rTMS), can induce LTP-like effects in humans. Traditionally, iTBS has been delivered using biphasic pulses. With advances in hardware, iTBS can be delivered using monophasic-like pulses via controllable pulse parameter rTMS. Emerging evidence suggests that iTBS administered with such monophasic pulses may produce more robust effects on cortical excitability compared to conventional biphasic stimulation. This study investigated the effects of monophasic versus biphasic iTBS on corticospinal excitability with the hypothesis that monophasic stimulation would produce greater facilitation of motor evoked potentials (MEPs). In a double-blinded, placebo-controlled, within-subjects design, 40 participants (equal males and females) received monophasic, biphasic, and sham iTBS in pseudo-randomized order. TMS measures (MEPs, intracortical facilitation (ICF), short-interval intracortical inhibition (SICI)) were recorded before and 10min following iTBS stimulation. No sex differences were observed. Monophasic iTBS significantly enhanced MEP amplitude. Biphasic iTBS did not significantly alter MEPs. SICI and ICF remained unchanged by iTBS. Responder analysis showed a higher frequency of facilitatory responses following monophasic iTBS and inhibitory responses following biphasic iTBS. Monophasic iTBS enhances corticospinal excitability. These findings support the use of monophasic iTBS to optimize neuromodulatory interventions and improve outcomes in brain stimulation therapies.

Cross-modal plasticity in a blind jazz pianist and prodigy.

Early adversity alters neurodevelopmental milestones in male and female rat pups and motor cortex morphology and gait in juveniles.

Mapping knowledge structure and emerging trends in non-invasive brain-computer interface for stroke rehabilitation.

Classic psychedelics and autism spectrum disorder: preclinical evidence, mechanistic insights and unresolved challenges.

Structural neuroimaging findings in migraine remain heterogeneous, and the impact of preventive treatments such as erenumab and onabotulinumtoxinA (OnabotA) on brain plasticity is poorly understood. We aimed to comprehensively characterize brain morphology, including less explored regions such as the cerebellum and corpus callosum (CC), compare people with migraine with healthy controls (HC), identify baseline predictors of treatment response, and evaluate longitudinal structural trajectories following preventive therapy. This prospective study included participants with migraine with ≥ 8 headache days/month eligible for erenumab or OnabotA, together with HC. T1-weighted MRI was acquired on 3T MRI scanners at baseline (M0) in all participants and repeated at 6 months (M6) in eligible participants with migraine. Regions of interest (ROIs) were segmented, and cortical thickness (CTh), cortical surface area (SA) and brain volume values were extracted using FastSurfer. Data were analysed using generalized linear mixed models (GLMM). Response was defined as a ≥ 50% reduction in monthly headache days at M6. We included 189 participants with migraine and 63 HC; 87.9% were female (222/252), and age was similar between groups (adjusted-p = 0.627). Compared with HC, individuals with migraine showed larger volumes in the mid-posterior (adjusted-p = 0.001) and central CC segments (adjusted-p = 0.030). 2) At baseline, non-responders (NR) showed higher CTh in the left parahippocampal gyrus than responders (R) (adjusted-p = 0.008). In addition, a significant response-by-treatment interaction was observed in the bilateral caudate volume: post-hoc contrast showed higher caudate volumes in OnabotA responders than in OnabotA NR (adjusted-p = 0.041 for both hemispheres), whereas no such difference was obsvered with erenumab. Longitudinally, several time-by-treatment interactions indicated different structural trajectories between treatments. In most of these regions, post-hoc contrasts showed lower M6 values in the erenumab group, including SA in the left fusiform, left pericalcarine, left rostral anterior cingulate, and right lingual regions, and volume in the bilateral cerebellar cortex, right hippocampus, and left amygdala. The left choroid plexus showed an opposite pattern, with increased volume in the erenumab group. Comparable longitudinal changes were not observed in the OnabotA group. Our results identify CC alterations and baseline parahippocampal and caudate morphometry as potential markers of migraine and treatment response. Erenumab and OnabotA showed different longitudinal structural trajectories, with more evident changes observed in the erenumab group in regions related to in pain, limbic, memory, and cerebellar processing. EudraCT: 2019-002224-32, Date: 2019-11-12. ID: 2020-003650-77 available at REEC, Date: 2021-02-09. ID: 2020-002639-31 available at REEC, Date: 2020-10-23.

Impaired cerebellar influence on motor cortical excitability and plasticity has been reported in cervical dystonia (CD) patients, accompanied by the absence of cerebellar brain inhibition (CBI). Polarity-specific modulation of CBI in healthy individuals using cerebellar transcranial direct current stimulation (ctDCS) suggested that ctDCS could normalize abnormal cerebellar output and improve clinical symptom severity in CD. The objective of this study was to determine whether anodal or cathodal ctDCS can modulate neurophysiological parameters of cortico-cortical, cerebello-cortical or afferent inhibition and improve motor symptom severity in CD patients. Fifteen patients with isolated CD participated in a randomized, double-blinded crossover study consisting of three sessions of anodal, cathodal, or sham ctDCS. Before and after each intervention, motor symptom severity and inhibitory circuits of the sensorimotor network were investigated using transcranial magnetic stimulation (TMS), including short-interval intracortical inhibition (SICI), short-latency afferent inhibition (SAI) and CBI. Baseline TMS measurements showed inhibitory influence of SICI (p < 0.001) and SAI (p < 0.001) in CD patients, whereas CBI had no inhibitory effect (p = 0.281). The different ctDCS interventions caused no significant modulation in any of the inhibitory TMS paradigms investigated. Similarly, motor symptom severity remained unchanged after the ctDCS interventions. A single session of ctDCS was not effective to modulate inhibitory circuits of the sensorimotor network in isolated CD patients. Future studies focusing on repetitive ctDCS interventions or multifocal stimulation protocols are needed to assess the influence on network excitability and connectivity as well as on motor symptoms.

Erythropoietin targets parvalbumin-positive inhibitory neurons and microglia to promote plasticity in the thalamic reticular nucleus.

Stroke leads to widespread brain connectivity changes, impacting areas both close and remote to the lesion. Post-stroke recovery dynamics are not fully understood. Investigating structural network reorganization over time can thus provide valuable information on adaptive and maladaptive neural plasticity changes on a subject-specific level. Four first-time ischemic stroke patients (3 M, aged 50-69 years) with upper-extremity motor impairment were examined using ultra-high field 7T MRI structural imaging protocols. For each patient, we performed longitudinal lesion quantification and white matter connectivity analysis at three critical timepoints associated with post-stroke recovery: within 1 week, at ~ 1 month, and at ~ 3 months. Using the structural MRI images, we generated patient-specific weighted structural connectivity matrices at each timepoint. We utilized the Schaefer-Yeo and Automated Anatomical Labeling atlases to derive both anatomical regions and resting-state networks based on pre-defined parcel assignments. We examined lesion evolution and white matter connectivity changes as disconnections, re-emerging connections, and existing connections with an increase in estimated connectivity strength over time. We further conducted exploratory edge-level analyses to examine the connectivity strength changes for each patient. Across all patients and timepoints, an increase in estimated connectivity strength of pre-existing connections dominated structural reorganization. Temporally, the four patients revealed distinct neural reorganization patterns. Patient 1 exhibited robust structural changes in the late ~1 to ~ 3 months stage, whereas Patient 2 in the early < 1 week to ~ 1 month stage. Patient 3 had continuous network growth, while Patient 4 demonstrated stable network reorganization. In our sample, the somatomotor and attention networks underwent the most dynamic reorganization. Somatomotor and salience/ventral attention regions exhibited increased connectivity strength, and in cortical stroke cases, dorsal attention regions demonstrated decreased connectivity strength. In this longitudinal case series, post-stroke neural network reorganization appears to be driven by an increase in estimated connectivity strength of surviving white matter connections, suggesting compensatory neuroplasticity. Adaptive changes were most evident in the somatomotor and salience/ventral attention networks within this sample, while the dorsal attention network suggested a more limited contribution to adaptive network changes. Individual differences in the timing and pattern or reorganization highlight the potential need for further research into personalized treatment approaches to promote adaptive recovery.

Chronic low back pain (CLBP) has been linked to maladaptive cortical plasticity in sensorimotor regions, which may contribute to pain persistence through less distinct ("smudged") somatotopic maps of afferent input from the back. However, empirical support for such functional reorganization, especially in the primary somatosensory cortex (S1), is limited. To delineate precise sensory representations of the back in humans and test for altered somatotopic processing in CLBP, we utilized an MR-compatible pneumatic vibration device and applied frequency-specific vibrotactile stimuli at nine thoracolumbar paraspinal sites in 45 patients with CLBP and 41 healthy controls (53 females in total). Representational similarity analysis was employed via a whole-brain searchlight method, and the neural representational patterns were contrasted against theoretical models including a segmental (based on anatomical proximity), simple (upper vs lower back division), and a random model. In addition, a machine learning classifier was trained to predict afferent input from the upper versus lower back in healthy controls and tested in CLBP patients. Both groups displayed well-organized segmental representations spanning somatosensory, motor, and posterior parietal cortices. Posterior parietal regions exhibited the best model fits, followed by S1. No evidence for differences in representational patterns between groups was found. In CLBP patients, these patterns did not show associations with pain duration, severity, and self-reported back perception. The classifier, trained on healthy controls, accurately predicted upper versus lower back afferent input in CLBP patients. These findings indicate preserved cortical maps of the back in CLBP, challenging the hypothesis of sensory cortical reorganization in this condition.

Psychedelics have emerged as powerful modulators of neural plasticity, yet whether the atypical psychedelic ibogaine can enhance plasticity remains poorly understood. Here, we investigated whether a single administration of ibogaine can reinstate juvenile-like experience-dependent plasticity in the adult mouse visual cortex, a canonical model for studying neuroplasticity. Adult mice were treated with ibogaine (40mg/kg, i.p.) or vehicle, and 24h later subjected to 4 days of monocular deprivation (MD). Behavioral visual acuity was quantified using the optomotor response test, and structural plasticity was assessed through dendritic spine density analysis following Golgi staining. Ibogaine alone did not alter visual acuity or dendritic spine density in non-deprived adults. However, when coupled with MD, ibogaine restored youthful levels of plasticity: MD significantly reduced visual acuity in the deprived eye and decreased dendritic spine density in the binocular visual cortex of ibogaine-treated, but not vehicle-treated, adult mice. To examine mechanistic correlates of these findings, we quantified perineuronal nets (PNNs), parvalbumin-positive interneurons (PVs), and inhibitory synaptic puncta labeled with the vesicular GABA transporter (vGAT). We found that ibogaine reduced PNN and PV staining intensity and density, decreased the proportion of PVs enwrapped by PNNs, and lowered vGAT-positive puncta density. These results show that ibogaine re-establishes experience-dependent plasticity in the adult visual cortex and that this effect is accompanied by reductions in structural and inhibitory "brakes" on plasticity. Our findings suggest that ibogaine's long-lasting therapeutic actions can arise, at least partially, from its ability to re-open windows of heightened cortical adaptability.

Objective.We proposelogLIRA, a novel method for the rejection of intracortical microstimulation artifacts in electrophysiological recordings specialized in the recovery of short-latency evoked activity. Additionally, we introduce a comprehensive comparison framework to evaluate the performance oflogLIRAagainst previously reported algorithms.Approach.Our method estimates the artifact profiles by means of a piece-wise linear interpolation between logarithmically distributed points. It handles signal saturation thanks to a dynamically adjusted blanking interval. Finally, it deals with residual secondary artifacts by clustering and common activity rejection. The artifact rejection proficiency oflogLIRAis evaluated against other state-of-the-art algorithms by means of a semisynthetic dataset acting as ground truth and enabling the computation of key performance metrics.Main results.The benchmark analysis highlights that our new method outperforms its competitors, enabling a robust recovery of short-latency evoked activity and, at the same time, minimizing the likelihood of introducing false positives as a consequence of misclassified residual artifacts. The results hold for very heterogeneous artifact profiles (with or without signal saturation) and across different combinations of mean artifacts rate and mean firing rate in the semisynthetic dataset. Additionally, we show the functioning oflogLIRAwith real-world data, where its capability to handle secondary artifacts and avoid inflated evoked responses is particularly evident.Significance.This work provides the scientific community with a valuable and powerful tool to improve the recovery of evoked responses, potentially contributing to a better understanding of functional connectivity and brain plasticity mechanisms inin vivoneural circuits as well as the advancement of therapeutic electrical neuromodulation techniques.