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Shirazpour S, Taheri F, Sepehri G, Zangiabadizadeh M, Zangiabadi M

Brain Behav. 2025 May

PMID:40341875

Abstract

The current study aimed to investigate the impacts of 8-week high-intensity interval training (HIIT) and Ritalin (RIT), alone and in combination, on cognitive functions and hippocampal oxidative parameters following chronic ethanol consumption in male rats.

Liu C, Hou M, Yu S, Wan Y, Liu Z

Brain Behav. 2025 May

PMID:40341797

Abstract

Freezing of gait (FOG) is a debilitating symptom in Parkinson's disease (PD) patients that severely impairs mobility. Rhythmic auditory stimulation (RAS) has demonstrated potential in improving gait, but the mechanisms underlying its efficacy remain unclear. This study explored the impact of RAS on brain function in PD patients with FOG using functional near-infrared spectroscopy (fNIRS) during an imagined walking task, with the aim of elucidating the underlying mechanisms involved.

Osorio S, Assaneo MF

PLoS One. 2025

PMID:40341725

Abstract

Music and speech encode hierarchically organized structural complexity at the service of human expressiveness and communication. Previous research has shown that populations of neurons in auditory regions track the envelope of acoustic signals within the range of slow and fast oscillatory activity. However, the extent to which cortical tracking is influenced by the interplay between stimulus type, frequency band, and brain anatomy remains an open question. In this study, we reanalyzed intracranial recordings from thirty subjects implanted with electrocorticography (ECoG) grids in the left cerebral hemisphere, drawn from an existing open-access ECoG database. Participants passively watched a movie where visual scenes were accompanied by either music or speech stimuli. Cross-correlation between brain activity and the envelope of music and speech signals, along with density-based clustering analyses and linear mixed-effects modeling, revealed both anatomically overlapping and functionally distinct mapping of the tracking effect as a function of stimulus type and frequency band. We observed widespread left-hemisphere tracking of music and speech signals in the Slow Frequency Band (SFB, band-passed filtered low-frequency signal between 1-8Hz), with near zero temporal lags. In contrast, cortical tracking in the High Frequency Band (HFB, envelope of the 70-120Hz band-passed filtered signal) was higher during speech perception, was more densely concentrated in classical language processing areas, and showed a frontal-to-temporal gradient in lag values that was not observed during perception of musical stimuli. Our results highlight a complex interaction between cortical region and frequency band that shapes temporal dynamics during processing of naturalistic music and speech signals.

Tsurukawa FK, Mao Y, Sanchez-Villalobos C, Khanna N, Crasto CJ

Sci Rep. 2025 May 8

PMID:40341634

Abstract

Developing effective treatments for Alzheimer's disease (AD) likely requires a deep understanding of molecular mechanisms. Integration of transcriptomic datasets and developing innovative computational analyses may yield novel molecular targets with broad applicability. The motivation for this study was conceived from two main observations: (a) most transcriptomic analyses of AD data consider univariate differential expression analysis, and (b) insights are often not transferable across studies. We designed a machine learning-based framework that can elucidate interpretable multivariate relationships from multiple human AD studies to discover robust transcriptomic AD biomarkers transferable across multiple studies. Our analysis of three human hippocampus datasets revealed multiple robust synergistic associations from unrelated pathways along with inconsistencies of gene associations across different studies. Our study underscores the utility of developing AI-assisted next-gen metrics for integration, robustness, and generalization and also highlights the potential benefit of elucidating molecular mechanisms and pathways that are important in targeting a single population.

Al-Sawasany AS, Fayed HM, Mahmoud BF, Elblehi SS, Ghazal NA

J Biochem Mol Toxicol. 2025 May

PMID:40341631

Abstract

Alzheimer's disease (AD) is the most common cause of dementia, a neurodegenerative disorder that progress overtime, which is best known for mood swings and loss of cognitive, behavioral and functional abilities. Quercetin is one of the most consumed flavonoids in the diet and has neuroprotective, anti-inflammatory and antioxidant effects. The purpose of this study was to assess the potential neurotherapeutic effect of quercetin and compare it with donepezil. 40 Wister male rats were used and separated into two main groups: Group I: control group; Group II: AD group, which was divided into four subgroups: Group IIA: untreated AD-rats; Group IIB: quercetin treated AD-rats; Group IIC: donepezil treated AD-rats and Group IID: combined group of quercetin and donepezil. Hydrated aluminum chloride (AlCl.6HO) solution (75 mg/kg/day) was administered orally for 6 weeks to induce the AD-like conditions. Morris water maze, behavior test, was used to monitor the cognitive function. Hippocampal tissues were excised for assessment of Alzheimer's parameters and blood samples were obtained for liver and kidney function assessment. According to the final findings, untreated rats presented significantly increased levels of amyloid β; tau protein; malondialdehyde; nuclear factor kappa-B; acetylcholinesterase activity, β-site amyloid precursor protein cleaving enzyme 1 upregulation and miRNA-124 downregulation. The best results of treatment were observed in the combination of donepezil and quercetin, as revealed by histopathological observations via H&E and Congo red stains. This study led to the conclusion that quercetin, by targeting several pathogenic pathways, could be used as an adjuvant drug with donepezil for AD treatment.

Küttner A, Uhlig M, Zwiky E, König P, Ptasczynski LE

J Psychiatry Neurosci. 2025 May-Jun

PMID:40341223

Abstract

Despite the prevalence and impact of body dysmorphic concerns on psychosocial functioning, there remains a scarcity of research examining the neurobiological and psychological correlates of these symptoms in healthy individuals. Given that previous studies on clinical body dysmorphic disorder (BDD) revealed brain structural and functional differences in limbic, frontal, and visual processing areas, as well as cognitive and emotional deficits, we sought to investigate the associations between grey matter volume (GMV), subclinical body dysmorphic symptom severity, alexithymia, and rumination.

Hadjiosif AM, Dajaj Y, Ranjan T, Smith MA

Sci Rep. 2025 May 8

PMID:40341213

Abstract

Short sub-100 ms visual feedback latencies are common in many types of human-computer interactions yet are known to markedly reduce performance in a wide variety of motor tasks from simple pointing to operating surgical robotics. It remains unclear, however, whether these latencies impair not only skilled motor performance but also the implicit sensorimotor learning that underlies its acquisition. Inspired by neurophysiological findings showing that cerebellar LTD and cortical LTP would both be disrupted by sub-100 ms latencies, we hypothesized that implicit sensorimotor learning may be particularly sensitive to these short latencies. Remarkably, we find that improving latency by just 60 ms, from 85 to 25 ms in continuous-feedback experiments, increases implicit learning by 50% and proportionally decreases explicit learning. This resulted in a dramatic reorganization of sensorimotor memory from a 45/55 to a 70/30 implicit/explicit ratio. This 70/30 ratio is more than double that observed in any previous study examining the effect of latency on sensorimotor learning, including a recent study which provided time-advanced visual feedback, suggesting that the low-latency continuous visual feedback we provided is critical for efficiently driving implicit learning. We go on to show that implicit sensorimotor learning is considerably more sensitive to latencies in the sub-100 ms range than to higher latencies, in line with the latency-specific neural plasticity that has been observed. This suggests a clear benefit for latency reduction in computer-based training that involves implicit sensorimotor learning and that across-study differences in computer-based experiments that have examined implicit sensorimotor learning might be explained by differences in unmeasured feedback latencies.

Nakai T, Kubo R, Nishimoto S

Commun Biol. 2025 May 8

PMID:40341201

Abstract

The variability in brain function forms the basis for our uniqueness. Prior studies indicate smaller individual differences and larger inter-subject correlation (ISC) in sensorimotor areas than in the association cortex. These studies, deriving information from brain activity, leave individual differences in cognitive structures based on task similarity relations unexplored. This study quantitatively evaluates these differences by integrating ISC, representational similarity analysis, and vertex-wise encoding models using functional magnetic resonance imaging across 25 cognitive tasks. ISC based on cognitive structures enables subject identification with 100% accuracy using at least 14 tasks. ISC is larger in the fronto-parietal association and higher-order visual cortices, suggesting subject-invariant cognitive structures in these regions. Principal component analysis reveals different cognitive structure configurations within these regions. This study provides evidence of individual variability and similarity in abstract cognitive structures.

Oussoren FK, van Leeuwen RB, Schermer TR, Hensen EF, Lammers MJW

BMJ Open. 2025 May 7

PMID:40341148

Abstract

The aetiology of sudden sensorineural hearing loss (SSNHL) is not certain in a significant number of cases. In 8%-31% of posterior fossa infarctions, acute hearing or vestibular loss precedes neurological symptoms. Also, several retrospective cohort analyses have indicated a higher chance of experiencing a stroke after SSNHL compared with the general population. This higher incidence of stroke suggests vascular involvement in the pathophysiology of SSNHL. The aim of this study is to evaluate the association of cardiovascular disease and idiopathic SSNHL (iSSNHL) by investigating the presence of cardiovascular risk factors and cerebral small vessel disease (CSVD), in patients with iSSNHL and compare this to controls.

Cuello AC, Do Carmo S

Handb Clin Neurol. 2025

PMID:40340070

Abstract

This chapter discusses the dependency of basal forebrain cholinergic neurons (BFCNs) on endogenous nerve growth factor (NGF) for the structural and physiologic maintenance of the neuronal cell somata, axonal projections, and terminal synapses. It covers the discovery of NGF and the occurrence of a CNS neurotrophin family and their cognate receptors and their signaling mechanisms. It concludes with a description of the NGF metabolic pathway and its dysregulation in Alzheimer disease (AD) and Down syndrome pathology, explaining the progressive atrophy of BFCNs, which starts at preclinical stages and is reflected in body fluid biomarkers.

Taza M, Schmitz TW, Spreng RN

Handb Clin Neurol. 2025

PMID:40340069

Abstract

In this chapter, we review evidence, derived predominantly from in vivo human MRI studies, that the basal forebrain (BF) and its projection system undergo structural changes across the continuum of Alzheimer disease (AD) progression. We examine how these changes are detectable from the earliest presymptomatic stages and continue into the prodromal and clinical phases of AD. The chapter begins with a brief overview of BF neuroanatomy before characterizing how changes to the BF and ascending cholinergic white matter projections parallel AD progression. In subsequent sections, we describe how these structural changes are exacerbated in the presence of amyloid and tau pathology, as well as in individuals at elevated genetic risk for AD. We conclude with a review of recent findings implicating the BF as a potential origin site for AD neuropathology and discuss the transsynaptic spread hypothesis of AD progression, from the BF to cortical projection targets.

Mufson EJ, Perez SE

Handb Clin Neurol. 2025

PMID:40340061

Abstract

Cholinergic basal forebrain (CBF) projection neurons within the nucleus basalis and striatal cholinergic interneurons degenerate in individuals with Down syndrome (DS). However, the neuropathobiology of these diverse cholinergic phenotypes remains underinvestigated. This review summarizes the alterations of cholinergic, neurotrophic survival and cell death factors as well as tau pathology and amyloidopathy, and their effects upon these cell types in DS. In trisomy, the developing cholinergic system remains stable, whereas the neurotrophic receptors are compromised between control and DS cases. Both cholinergic neuronal phenotypes display severe cellular degeneration in both adult and the aged people with DS. Although developing cholinergic striatal neurons display a similar morphology between phenotypes, cholinergic striatal neurons appear dystrophic in adults with DS. Both cholinergic cell types display tau tangle pathology in elders with DS. Novel findings suggest that alterations in plasma and cerebral spinal fluid levels of proNGF, NGF metabolites, and select classes of neuronal genes are potential biomarkers to distinguish nondemented from demented people with DS. Compounds that target cholinergic pathways, TrkA agonists, p75/proNGF small molecular antagonists, NGF metabolites, and select gene ontology classes are potential targets to slow degeneration of the CBF memory connectome in DS with translation to AD.

Geula C, Ayala I, Gefen T, Mesulam MM

Handb Clin Neurol. 2025

PMID:40340056

Abstract

The mammalian nervous system contains several cholinergic cell groups. The most extensive of these are the cholinergic neurons of the basal forebrain (BFCN). The human BFCN are organized into four cell groups (Ch): Ch1, centered around the medial septum (Ch1-ms), Ch2 in the vertical limb of the diagonal band of Broca (Ch2-dbv), Ch3 around the horizontal limb of the diagonal band of Broca (Ch3-dbh), and Ch4 in the nucleus basalis of Meynert (Ch4-nbM). The Ch4-nbM is the largest of these neuronal groups and is parcellated into sectors based on grouping of cells and anatomic landmarks. Consistent with their cholinergic phenotype, BFCN cell groups are rich in synthetic enzyme choline acetyltransferase (ChAT) and hydrolytic enzyme acetylcholinesterase (AChE). They also have high content of nerve growth factor receptors and calcium-binding protein calbindin-D. In the monkey brain, each BFCN cell group has its preferred cortical targets. Ch1-ms and Ch2-dbv neurons project to the hippocampus, Ch3-dbh neurons to the olfactory bulb, and Ch4-nbM neurons to the entire cortical mantle and the amygdala. Despite extensive projections to all cortical areas, only limbic cortical components project back to the BFCN. Staining for AChE activity and ChAT immunoreactivity visualizes a plexus of cortical cholinergic axons. The highest density of cholinergic axons is found in limbic and paralimbic cortical regions, intermediate density in association cortical areas, and lowest density in primary sensory and motor regions. Acetylcholine interacts with cortical muscarinic and nicotinic receptors, each with varied regional distribution, to produce its effects. Functionally, the BFCN cell groups are implicated in several behaviors including sleep and arousal, mood and affect, and particularly attention and memory. In summary, the BFCN form a highly complex neuronal system with extensive cortical projections that influence cortical activity and cognitive function.

McClung CA

Neuron. 2025 May 7

PMID:40339564

Abstract

In this issue of Neuron, Pignatelli et al. find that ketamine reverses stress-induced changes in excitatory synapses in nucleus accumbens D1 dopamine receptor-expressing medium spiny neurons (D1-MSNs) and that these changes are necessary for the treatment of anhedonia-like behavior.

Zhou C, Gao X, Tan L

Neuron. 2025 May 7

PMID:40339563

Abstract

Sonoda et al. showed that dLGN neurons exhibit long-lasting shifts of tuning preference toward selective features experienced during the classical critical period. They demonstrated that this plasticity results from feedforward-input refinement, revealing a different form of experience-dependent plasticity compared to V1.

Ma ZZ, Guzikowski NJ, Kim JW, Kavalali ET, Monteggia LM

Science. 2025 May 8

PMID:40339008

Abstract

Repeated ketamine treatment to maintain a rapid antidepressant effect can lead to side effects over time, highlighting an unmet clinical need for sustaining this drug's antidepressant action from a single administration. Ketamine-induced synaptic potentiation at CA3-CA1 synapses has been proposed to be a key synaptic substrate for antidepressant action. Here, we found that ketamine-induced CA3-CA1 synaptic potentiation could be augmented by transiently increasing extracellular signal-regulated kinase (ERK) activity through pharmacological inhibition of dual-specificity phosphatases 6 (DUSP6). The antidepressant-like behavioral effects of acute ketamine treatment were extended by DUSP6 inhibition for up to 2 months. The selective deletion of tropomyosin receptor kinase B (TrkB) in excitatory neurons abolished these DUSP6 inhibition-mediated synaptic and behavioral effects. These data suggest that ketamine's rapid antidepressant effects can be sustained by selectively targeting downstream intracellular signaling.

Schmid D, Neumann H

PLoS Comput Biol. 2025 May

PMID:40338986

Abstract

Object-basd visual attention marks a key process of mammalian perception. By which mechanisms this process is implemented and how it can be interacted with by means of attentional control is not completely understood yet. Incremental binding is a mechanism required in demanding scenarios of object-based attention and is experimentally well investigated. Attention spreads across a representation of the visual object and labels bound elements by constant up-modulation of neural activity. The speed of incremental binding was found to be dependent on the spatial arrangement of distracting elements in the scene and to be scale invariant giving rise to the growth-cone hypothesis. In this work, we propose a neural dynamical model of incremental binding that provides a mechanistic account for these findings. Through simulations, we investigate the model properties and demonstrate how an attentional spreading mechanism tags neurons that participate in the object binding process. They utilize Gestalt properties and eventually show growth-cone characteristics labeling perceptual items by delayed activity enhancement of neuronal firing rates. We discuss the algorithmic process underlying incremental binding and relate it to our model computations. This theoretical investigation encompasses complexity considerations and finds the model to be not only of explanatory value in terms of neurophysiological evidence, but also to be an efficient implementation of incremental binding striving to establish a normative account. By relating the connectivity motifs of the model to neuroanatomical evidence, we suggest thalamo-cortical interactions to be a likely candidate for the flexible and efficient realization suggested by the model. There, pyramidal cells are proposed to serve as the processors of incremental grouping information. Local bottom-up evidence about stimulus features is integrated via basal dendritic sites. It is combined with an apical signal consisting of contextual grouping information which is gated by attentional task-relevance selection mediated via higher-order thalamic representations.

Surkar SM, Lin CC, Trotter B, Phinizy T, Sylcott B

PLoS One. 2025

PMID:40338969

Abstract

Dual-task (DT) training, which involves the simultaneous execution of cognitive and motor tasks, has been shown to influence task performance and cortical activation, yet evidence on the effects of DT training and cortical activation for complex postural control tasks remains limited. This study investigated the immediate and retention effects of a one-week DT training program on DT learning, performance in DT and single-task conditions, and activation in bilateral prefrontal (PFC) and vestibular cortices in healthy young adults. Eighteen individuals (age = 22.39 ± 1.73 years) participated in the study. The DT paradigm involved a dynamic stability platform (motor task) paired with either a simple or complex auditory reaction time (RT) task (cognitive). Participants completed 20-25 minutes of DT training (18 trials/day) across five consecutive days. DT performance was measured by the duration participants maintained the stability platform within 3 degrees of the horizontal while responding to auditory stimuli. Single-task motor and cognitive performances were also assessed. Cortical activation in the PFC and vestibular cortices was measured using functional near infrared spectroscopy (fNIRS), tracking changes in oxygenated hemoglobin (HbO) concentrations. Pre-training, post-training, and one-week follow-up testing was conducted. The results demonstrate that DT training significantly improves and retains DT performance, likely due to a reduction in cognitive-motor interference. Additionally, DT training led to decreased activation in the bilateral PFC and vestibular cortices, specifically for complex DT condition, suggesting enhanced attentional resource allocation and optimized vestibular input processing, indicative of neural efficiency. Notably, these training effects also transferred to single-task cognitive and motor performances, with corresponding reductions in PFC and vestibular cortex activation, despite the lack of direct training on these tasks. This study advances our understanding of the neural mechanisms underlying DT training and underscores the critical role of practice in optimizing cognitive-motor efficiency.

He T, Gong X, Wang Q, Zhu X, Liu Y

Elife. 2025 May 8

PMID:40338213

Abstract

The ability of cortical circuits to adapt in response to experience is a fundamental property of the brain. After exposure to a moving dot sequence, flashing a dot as a cue at the starting point of the sequence can elicit successive elevated responses even in the absence of the sequence. These cue-triggered elevated responses have been shown to play a crucial role in predicting future events in dynamic environments. However, temporal sequences we are exposed to typically contain rich feature information. It remains unknown whether the elevated responses are feature-specific and, more crucially, how the brain organizes sequence information after exposure. To address these questions, participants were exposed to a predefined sequence of four motion directions for about 30 min, followed by the presentation of the start or end motion direction of the sequence as a cue. Surprisingly, we found that cue-triggered elevated responses were not specific to any motion direction. Interestingly, motion direction information was spontaneously reactivated, and the motion sequence was backward replayed in a time-compressed manner. These effects were observed even after brief exposure. Notably, no replay events were observed when the second or third motion direction of the sequence served as a cue. Further analyses revealed that activity in the medial temporal lobe (MTL) preceded the ripple power increase in visual cortex at the onset of replay, implying a coordinated relationship between the activities in the MTL and visual cortex. Together, these findings demonstrate that visual sequence exposure induces twofold brain plasticity that may simultaneously serve for different functional purposes. The non-feature-specific elevated responses may facilitate general processing of upcoming stimuli, whereas the feature-specific backward replay may underpin passive learning of visual sequences.

Tan KWS, Stalin A, Park ASY, Dalton K, Thompson B

J Vis. 2025 May 1

PMID:40338177

Abstract

Animal models indicate that exercise promotes visual cortex neuroplasticity; however, results from studies that have explored this effect in humans are mixed. A potential explanation for these discrepant results is the relative timing of exercise and the task used to index neuroplasticity. We hypothesized that a close temporal pairing of exercise and training on a vision task would enhance perceptual learning (a measure of neuroplasticity) compared to a non exercise control. Thirty-two participants (mean age = 31 years; range, 20-65; SD = 11.1; 50:50 sex ratio) were randomly assigned to Exercise or Non Exercise groups. The Exercise group alternated between moderate cycling along a virtual course and training on a peripheral crowding task (5 minutes each, 1 hour total intervention), and the Non Exercise group alternated between passive viewing of the virtual cycling course and the vision task. The protocol was repeated across 5 consecutive days. Both groups exhibited reduced visual crowding after 5 days of training. However, there was no difference in perceptual learning magnitude or rate between groups. Translation of the animal exercise and visual cortex neuroplasticity results to humans may depend on a range of factors, such as baseline fitness levels and the measures used to quantify neuroplasticity.