bluuebunny/crossref_metadata_2025_split huggingface dataset:
IMPAIRED RESTING-STATE ANTERIOR PREFRONTAL FUNCTIONAL CONNECTIVITY ASSOCIATED WITH PROSPECTIVE MEMORY DEFICITS IN SCHIZOPHRENIA
Authors: Zhou *Fuchun , Wang Nan , Li Hang , Zhang Zhifang , Wang Chuanyue 
Published: February 2025

Abstract

Background
Prospective memory (PM) deficit is one of the most common cognitive impairments of patients with schizophrenia spectrum disorders (SSDs). PM deficits have been associated with social functioning impairment, poor adherence to drugs and adverse clinical outcome. Previous studies have atributed the PM deficits in schizophrenia to the failure of cue detection and intention retrieval. In healthy people, these cognitive processes reflect the ability of strategic monitoring, which heavily rely on the functional network of anterior prefrontal cortex (aPFC) and related brain regions. This suggests that PM deficits in SSDs patients may be due to aPFC functional connectivity impairments.

Aims & Objectives
The aim of the present study is to compare the resting-state aPFC functional connectivity between patients with SSDs and healthy controls, and to examine whether the PM deficits in SSDs patients are due to aPFC functional connectivity impairments.

Method
Sixty-three SSDs patients and 32 healthy controls (HCs) formed the study sample. Time- and event-based PM (TBPM and EBPM) performance were measured with the Chinese version of the Cambridge Prospective Memory Test (C-CAMPROMPT). Patients' clinical symptoms were evaluated with the Positive and Negative Symptom Scale (PANSS). All participants underwent resting-state functional magnetic resonance imaging (fMRI). Left and right BA 10 were chosen as seeds to perform seed-based whole brain voxels resting-state functional connectivity analyses.

Results
Compared to HCs, SSDs patients demonstrated significantly worse PM performance and attenuated functional connectivity between right aPFC and precuneus (x= -9, y= -51, z=45), a key hub of the default mode. The correlation analysis results showed that the aforementioned functional connectivity in the SSDs group was significantly positively correlated with EBPM parformance (r= 0.319, P=0.013). No significant correlation analysis results were found between the functional connectivity and EBPM within the HC group.

Discussion & Conclusion
The results indicate that aPFC resting-state networks are affected in SSDs patients. The reduced magnitude of resting state functional connectivity between right aPFC and precuneus is a key marker of information processing failure underlying PM impairments in SSDs patients.
WHITE MATTER ABNORMALITIES OF THE FRONTAL-STRIATAL-THALAMIC CIRCUITS IN INDIVIDUALS WITH ATTENUATED POSITIVE SYMPTOM SYNDROMES A PROBABILISTIC TRACTOGRAPHY STUDY
Authors: Bo *Qijing , Chen Zhenzhu , Wang Chuanyue 
Published: February 2025

Abstract

Background
Attenuated positive symptoms syndrome (APSS) is a risk state preceding psychosis. Disturbances in the frontal-striatal-thalamic circuit have been implicated in the neuropathology of APSS. This study aimed to systematically investigate white matter (WM) alterations in the frontal -striatal- thalamic circuit in APSS.

Methods
Diffusion magnetic resonance imaging (dMRI) and T1-weighted images were acquired from 43 individuals with APSS and 50 healthy controls (HCs). The dMRI data were preprocessed using FSL software. Brainnetome Atlas (BNA) was utilized to extract regions of interest (ROIs) in the frontal lobe, striatum, and thalamus. Bidirectional probabilistic tractography was performed to construct the frontal-striatal-thalamic circuit. Multiple linear regression was employed to compare the connectivity probability (CP) and diffusion index values between the APSS and HC groups.

Results
Compared to HCs, individuals with APSS exhibited significantly lower CP values in right Orbital gyrus_area 13- right nucleus accumbens (R: OrG_A13-NAC) fiber tract. Higher mean diffusivity values were observed in the L: OrG_A13-NAC and left ventral caudate– left caudal temporal thalamus (L: vCa- cTtha) fiber tract. Additionally, higher radial diffusivity values were found in the R: NAC-OrG_A13 fiber tract, while higher axial diffusivity values were observed in multiple frontal lobe ROIs-striatum ROIs and striatum ROIs-thalamus ROIs fiber tracts. No significant differences were found in fractional anisotropy values.

Conclusions
Individuals with APSS demonstrated reduced fiber connection strength, impaired myelin and inflammatory changes in the R: NAC-OrG_A13 fiber tract, and possible inflammatory changes in the L: vCa-cTtha fiber tract. These alterations may contribute to the neuropathology of APSS. Additionally, increased fiber coherence in multiple fiber tracts suggests potential compensatory mechanisms.
OXYTOCIN-INDUCED INCREASES IN CYTOKINES AND CLINICAL EFFECT ON THE CORE SOCIAL SYMPTOMS OF AUTISM
Authors: Wakuda *Tomoyasu , Benner Seico , Uemura Yukari , Kojima Masaki , Kameno Yosuke , Kuwabara Hitoshi , Yamasue Hidenori ,   +32 Co-Authors
Published: February 2025

Abstract

Background
Oxytocin may provide a novel treatment for the core symptoms of autism spectrum disorder (ASD). However, previous results regarding the efficacy of repeated or higher dose oxytocin are controversial, and the underlying mechanisms including interactions with other molecules remain unclear.

Aims & Objectives
The current study is aimed to clarify whether repeated oxytocin alter plasma cytokine levels in relation to clinical improvements of autism social core symptom.

Method
We analyzed cytokine concentrations using comprehensive proteomics of plasmas of 207 adult males with high-functioning ASD collected from two independent multi-center large-scale randomized controlled trials (RCTs): Testing effects of 4-week intranasal administrations of TTA-121 (A novel oxytocin spray with enhanced bioavailability: 3U, 6U, 10U, or 20U/day) and placebo in the crossover discovery RCT; 48U/day Syntocinon or placebo in the parallel-group verification RCT.

Results
Among the successfully quantified 17 cytokines, 4 weeks TTA-121 6U (the peak dose for clinical effects) significantly elevated IL-7 (9.74, 95% confidence interval [CI] 3.59 to 15.90, False discovery rate corrected P (PFDR) = 0.009), IL-9 (56.64, 20.46 to 92.82, PFDR = 0.017) and MIP-1b (18.27, 4.96 to 31.57, PFDR = 0.017) compared with placebo. Inverted U-shape dose-response relationships peaking at TTA-121 6U were consistently observed for all these cytokines (IL-7: P = 0.025; IL-9: P = 0.002; MIP- 1b: P = 0.010). Increased IL-7 in participants with ASD after 6 weeks oxytocin administration compared with placebo was verified in the confirmatory Syntocinon trial dataset (19.74, 0.31 to 39.18, P = 0.047). Furthermore, the changes in all these cytokines during 4 weeks of TTA-121 10U administration revealed correlations with changes in reciprocity score, the original primary outcome, observed during the same period (IL-7: r = −.347, P = 0.089; IL-9: r = −.489, P = 0.013; MIP-1b: r = −.527, P = 0.007).

Discussion & Conclusion
These findings provide the first evidence for the role of interaction between oxytocin and neuroinflammation in the treatment of ASD core social symptoms, and support the potential role of this interaction as a novel therapeutic seed.
THE PHARMACOLOGICALLY DIVERSE HUMAN BRAIN: HOW NEUROSIGNALLING SYSTEMS REGULATE NEUROTYPICAL AND NEURODIVERGENT RESTING-STATE NETWORKS
Authors: Whelan *Tobias Patrick , Franca Lucas G S , Dimitrov Mihail , Mulcrone Naoise , Puts Nicolaas A , Daly Eileen , Murphy Declan G M , Mcalonan Grainne M 
Published: February 2025

Abstract

Background
Functionally inter-connected large-scale brain networks underpin complex human behaviour and a wide range of alterations in this landscape have been consistently reported in psychiatric and neurodevelopmental conditions, including autism. Evidence from preclinical and correlational human studies suggest that these differences arise from underlying differences in neurotransmitter systems. However, to directly assess how a given neurotransmitter system modulates functional connectivity, we need to change it and observe a shift in network connectivity.

Aims & Objectives
To report on how resting-state connectivity is differentially modulated by different drug classes and how responses differ between autistic and non-autistic individuals.

Methods
Here we establish a common framework to capture the modulation of functional connectivity within and between brain functional networks by neurosignalling systems targeted by a range of pharmacological probes. Alterations in functional connectivity are reported for seven cortical networks following activation of the serotonin, dopamine, opioid, cannabinoid and glutamate-GABA systems in neurodiverse (autistic and non-autistic) individuals. Reproducible differences in resting-state network functional connectivity, including both hyper- and hypoconnectivity of within- and between-network interactions, are reported in autism. Thus, we also assessed whether there are group-level network responsivity differences between autistic and non-autistic participants to drug challenge, or whether the response profile was primarily individual/ heterogeneous in either group.

Results
One common finding across pharmacological probes was that networks with reproducible baseline differences in autism (e.g. sensory and attentional networks) were also those that respond differently to drug challenge. Broadly, the cannabinoid compounds (cannabidiol and cannabidivarin) decreased functional connectivity in autistic individuals compared to non-autistic controls. By contrast, the other compounds such as the GABAergic drugs AZD7325 & arbaclofen (which activate GABAA and GABAB receptors, respectively), increased functional connectivity in autistic individuals relative to non-autistic controls.

Discussion & Conclusion
This is important to not only to advance our understanding of how neurotransmitter systems regulate fundamental functional networks in both the neurotypical and neurodivergent brain, but to provide a common framework for evaluating pre-existing and novel neuro-active compounds in the living human brain. We hope this work can be extended to form the basis of a human neuropharmacological reference library of neuro-active compounds across individuals and diagnoses.
RELATIONSHIP BETWEEN CEREBELLAR VOLUME AND PSYCHOLOGICAL FACTORS OF NORMAL YOUNG ADULTS
Authors: Moon *Seok Woo 
Published: February 2025

Abstract

Aims & Objectives
There have been no studies about the relationship between cerebellar volume and various psychological factors for normal subjects. This study analyzed the relationship between the cerebellar volume of normal adults in the third decade of life (20-29 years) and various psychological factors.

Methods
The cerebellar volume of 118 subjects (mean age, 23 ± 2.6 years), including 58 males (mean age, 24 ± 2.8 years) and 60 females (mean age, 21.9 ± 2.1 years), was measured using magnetic resonance imaging (MRI). The following tests were performed on all subjects: the Symptom Checklist-90-R (SCL-90-R), the Component of Type A Behavior, the State Anxiety Inventory from Korean YZ, the Sixteen Personality Factor (16PF), and the Self-rating Depression Scale (SDS). Using linear regression analysis, the relationship between cerebellar volume and psychological factors was analyzed.

Results
Without considering gender differences, as the tendency toward type A personality increased and the state of anxiety and superego strength increased, cerebellar volume decreased. As ego strength increased, cerebellar volume increased. When considering gender differences, as male phobic anxiety and ambition increased, cerebellar volume decreased. As female hostility, tenseness, and the state of anxiety increased, cerebellar volume decreased.

Discussion & Conclusion
This study also indicated that cerebellar volume or changes in cerebellar volume could be one of parameters which can diagnose the possibility of psychological diseases.
PREDICTION OF POSTOPERATIVE DELIRIUM BY BLOOD METABOLOME
Authors: Arai *Naohiro , Sugiura Yuki , Nakajima Shinichiro , Wada Masataka , Moriyama Sotaro , Mimura Yu , Takayama Kousuke , Niinomi Kanta , Boku Shuken , Mimura Masaru , Takebayashi Minoru , Uchida Hiroyuki , Noda Yoshihiro 
Published: February 2025

Abstract

Background
Delirium is a notable risk factor for cognitive dysfunction and poor prognosis. Despite its importance, there is currently no established blood marker that can predict postoperative delirium in the preoperative period.

Aims & Objectives
We aimed to examine that water-soluble metabolites, lipids, and cytokines in peripheral blood could uniquely classify postoperative delirium. In addition, we investigated whether changes in neuroinflammation-related and water-soluble metabolites in the indoleamine 2,3-dioxygenase (IDO) pathway could predict postoperative delirium.

Method
We designed a prospective cohort study of postoperative delirium and received approval from the Keio University School of Medicine Ethics Committee in December 2017. We used a comprehensive metabolomics and cytokine panel analysis involving 18 subjects in the delirium group and 24 subjects in the non-delirium group to determine whether preoperative blood metabolites, lipids, and cytokines could predict postoperative delirium. We also performed non-targeted metabolomics to investigate unanticipated small molecular weight metabolites in addition to IDO pathway metabolites and their correlations with cytokines indicative of an activated immune state. In addition, we conducted an in vitro experiment to test secretion with T-cell receptor stimulation on T cells.

Results & Discussion
We found that preoperative levels of amino acid catabolites, especially tryptophan catabolites produced via the IDO pathway, were higher in the delirium group than in the non-delirium group. These catabolites were validated as reliable predictors of postoperative delirium. Interestingly, the delirium group had elevated levels of tryptophan catabolites even before surgery, but only a limited increase in these levels was observed postoperatively. This suggests that the tryptophan catabolic pathway may be activated preoperatively in patients at high risk for developing delirium. In addition, our non-targeted metabolomic analysis identified a set of preoperatively elevated gamma-glutamyl dipeptides as significant discriminators of postoperative delirium. In vitro experiments showed that T- cell receptor stimulation resulted in increased tryptophan metabolism and specific gamma-glutamyl dipeptide secretion, which may explain increased metabolic byproducts in postoperative delirium.

Conclusion
Our study highlights the potential of blood concentrations of amino acid catabolites and dipeptides, including those secreted extracellularly upon T-cell activation, as reliable predictors of postoperative delirium.
SHORTENING OF TELOMERE LENGTH MAY BE ASSOCIATED WITH INFLAMMATORY CYTOKINES IN PATIENTS WITH BIPOLAR DISORDER
Authors: Wang *Tzu-Yun , Wang Shao-Ming , Chang Yun-Hsuan , Lu Ru-Band , Chang Hui Hua 
Published: February 2025

Abstract

Background
Bipolar disorder (BD) is hypothesized to be associated with accelerated biological aging. Telomere length (TL) is a biomarker of aging, and although TL reduces with each cell division, the shortening rate may be affected by allostatic load and inflammation. We hypothesized that BD patients may have TL shortening and levels of inflammatory markers may be associated with TL.

Aims & Objectives
We aimed to investigate whether there is a shortening of TL in BD patients and the association between TL shortening and inflammatory markers.

Method
BD patients and healthy controls (HC) were recruited. The leukocyte TL and plasma levels of cytokines [tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-8, IL-6, IL-10, transforming growth factor (TGF)-β1] and brain-derived neurotrophic factor (BDNF) was assessed.

Results
One hundred thirty-seven BD patients and 118 HC were enrolled. The TL was not significantly different between BD and HC after covarying for potential confounding factors (P =0.79). The TL was significantly negatively associated with age (β= -0.006, P&lt;0.001). In addition, the log TNF-α levels were significantly negatively associated with the TL (β=-0.42, P=0.009), whether in BD (β=-1.59, P=0.02) or in HC (β=-0.34, P=0.05).

Discussion & Conclusion
We found a significant association between TNF-α levels and TL shortening in both BD patients and HC participants. However, TL shortening was not found in BD patients. Further enlargement of the sample size and controlling for the heterogeneity of BD participants will be needed.
SOCIAL INTERACTION SUPPRESSES COCAINE RELAPSE BY REGULATING DAERGIC ENGRAM INPUT OF VENTRAL TEGMENTAL AREA
Authors: Zheng *Wei , Lu Tangsheng , Xue Yanxue , Lu Lin 
Published: February 2025

Abstract

Purpose
Addiction is a chronic relapsing brain disease, characterized by a high susceptibility to relapse once returns to the original living environment even after an extended period of abstinence. Positive social interactions are believed to have therapeutic potential in managing drug addiction by shifting the drug reward back onto social reward. However, the neural mechanisms underlying social interaction’ s therapeutic effects against relapse are poorly understood. The dopamine (DA) activity of Ventral tegmental area (VTA) mediates both the reinforcing properties of social reward and drugs of abuse. Therefore, we hypothesized that distinct subpopulations of DAergic neurons in the VTA may play different roles in the process of social anti-relapse.

Methods
We employed the cocaine self- administration as a relapse model in rats, and combined Targeted Recombination in Active Populations (TRAP), immunofluorescence, fiber photometry recording, and chemical genetics to explore the involvement of subpopulations of DAergic neurons during social interaction-mediated relapse prevention.

Results
We found that social interaction significantly inhibited the spontaneous recovery of cocaine seeking after cocaine self-administration extinction training in rats. While both social interaction and relapse of cocaine seeking reliably elicited obvious Ca2+ level increase in the TH neurons of VTA and induced DA relapse in nucleus accumbens (NAc), both the increase of Ca2+ level in the TH neurons of VTA and DA release in NAc induced by active cocaine relapse were significantly reduced after social interaction. Furthermore, the subpopulations of DAergic neurons in the VTA which encoded social interaction and relapse were distinct and anatomically segregated. Lastly, capturing and reactivating the specific subpopulation of DAergic neurons in the VTA encoding social interaction significantly inhibited cocaine relapse.

Conclusion
This study provided the evidence that distinct subpopulations of DAergic neurons in the VTA are involved in social interaction and relapse, and selective activation of the memory engram of social interaction in the VTA effectively inhibited drug relapse. Future studies will explore the input of DAergic neurons engram in the process of social interaction’ s therapeutic effects against cocaine relapse by combining mini scope, cross-synaptic engram tracer, brain patch clamp, and optogenetic, and reveal the circuitry mechanism of natural reward and drug reward interaction.
MEMORY CONSOLIDATION DRIVES THE ENHANCEMENT OF REMOTE COCAINE MEMORY VIA PREFRONTAL CIRCUIT
Authors: Xiaoxing *Liu , Tangsheng Lu , Ying Han , Lin Lu 
Published: February 2025

Abstract

Background
Forming memories are essential for survival, guiding our behaviors based on past experience. The expression of most these memories typically gradually weakens over time as an adaptive process of forgetting. Whereas, in some types of maladaptive memories, such as the drug-cue associated memories which account for the risk of drug relapse, their expression is progressively enhanced from recent memory to remote during prolonged time.

Aims & Objectives
To investigate the neural circuit underpinnings of the enhancement of remote cocaine-cue associated memory during abstinence.

Method
We used cocaine self-administration model in rats, together with Ca2+ imaging, immunofluorence, chemogenetic interventions, circuit tracing, and three-dimensional reconstruction of dendritic spine morphologies.

Results
We found a progressive increase in the response of prelimbic cortex (PrL) CaMKⅡ neurons to cues during 30-day abstinence. Dendritic spine maturation in the PrL relied on the basolateral amygdala (BLA) input during the early period of consolidation, and chronic inhibition of BLA-PrL circuit during abstinence day 1 to 14 could prevent cocaine seeking on day 30.

Discussion & Conclusion
These findings indicate that memory consolidation drives the enhancement of remote cocaine memory through a time-dependently increase in activity and maturation of PrL CaMKⅡ neurons receiving a sustained BLA input. We propose that the BLA may function as a cache that integrates the strong association between cocaine and related cues, and during system consolidation BLA can convey this information to PrL for long-term storage. Remarkably, during the early period post- training, more mature and stable dendritic spine plasticity which occurred in PrL neurons receiving BLA input possibly makes the association information abnormally consolidated, inducing stronger response when cue exposure at remote time and leading to enhancement of remote cocaine memory.