Biological Psychiatry-Cognitive Neuroscience and Neuroimaging最新文献

英文中文

Modulation of Cerebellar-Cortical Connectivity Induced by Modafinil and Its Relationship With Receptor and Transporter Expression 莫达非尼对小脑-皮层连接性的调节及其与受体和转运体表达的关系

IF 5.7 2区医学 Q1 NEUROSCIENCES

Biological Psychiatry-Cognitive Neuroscience and Neuroimaging

Pub Date : 2025-03-01 DOI: 10.1016/j.bpsc.2024.11.010

Stefano Delli Pizzi , Federica Tomaiuolo , Antonio Ferretti , Giovanna Bubbico , Valeria Onofrj , Stefania Della Penna , Carlo Sestieri , Stefano L. Sensi

Background

Modafinil is primarily used to treat narcolepsy but is also used as an off-label cognitive enhancer. Functional magnetic resonance imaging studies indicate that modafinil modulates the connectivity of neocortical networks primarily involved in attention and executive functions. However, much less is known about the drug’s effects on subcortical structures. Following preliminary findings, we evaluated modafinil’s activity on the connectivity of distinct cerebellar regions with the neocortex. We assessed the spatial relationship of these effects with the expression of neurotransmitter receptors/transporters.

Methods

Patterns of resting-state functional magnetic resonance imaging connectivity were estimated in 50 participants from scans acquired pre- and postadministration of a single (100 mg) dose of modafinil (n = 25) or placebo (n = 25). Using specific cerebellar regions as seeds for voxelwise analyses, we examined modafinil’s modulation of cerebellar-neocortical connectivity. Next, we conducted a quantitative evaluation of the spatial overlap between the modulation of cerebellar-neocortical connectivity and the expression of neurotransmitter receptors/transporters obtained by publicly available databases.

Results

Modafinil increased the connectivity of crus I and vermis IX with prefrontal regions. Crus I connectivity changes were associated with the expression of dopaminergic D₂ receptors. The vermis I–II showed enhanced coupling with the dorsal anterior cingulate cortex and matched the expression of histaminergic H₃ receptors. The vermis VII–VIII displayed increased connectivity with the visual cortex, an activity associated with dopaminergic and histaminergic neurotransmission.

Conclusions

Our study reveals modafinil’s modulatory effects on cerebellar-neocortical connectivity. The modulation mainly involves crus I and the vermis and spatially overlaps the distribution of dopaminergic and histaminergic receptors.

背景：莫达非尼主要用于治疗嗜睡症，但也可作为标签外的认知增强剂。功能磁共振成像（fMRI）研究表明，莫达非尼能调节主要参与注意力和执行功能的新皮质网络的连接。然而，人们对这种药物对皮层下结构的影响却知之甚少。根据初步研究结果，我们评估了莫达非尼对不同小脑区域与新皮层连接的影响。我们评估了这些影响与神经递质受体/转运体表达的空间关系：方法：我们对50名参与者在服用单次（100毫克）莫达非尼（25人）或安慰剂（25人）前后获得的扫描结果进行了静息态fMRI（rs-fMRI）连通性模式估算。以特定的小脑区域为种子进行体素分析，我们研究了莫达非尼对小脑-皮层连通性的调节作用。接下来，我们对小脑-皮层连通性的调节与通过公开数据库获得的神经递质受体/转运体的表达之间的空间重叠进行了定量评估：莫达非尼增强了Crus I和Vermis IX与前额叶区域的连接。Crus I连接性的变化与多巴胺能D2受体的表达有关。Vermis I-II 显示与背侧前扣带回皮层的耦合增强，并与组胺能 H3 受体的表达相匹配。Vermis VII-VIII 显示与视觉皮层的连接性增强，这种活动与多巴胺能和组胺能神经传递有关：我们的研究揭示了莫达非尼对小脑-皮层连接的调节作用。结论：我们的研究揭示了莫达非尼对小脑-皮层连通性的调节作用，这种调节作用主要涉及Crus I和Vermis，并在空间上与多巴胺能受体、组胺能受体和5-羟色胺转运体的分布重叠。

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引用次数: 0

Increased Amygdala Activation During Symptom Provocation Predicts Response to Combined Repetitive Transcranial Magnetic Stimulation and Exposure Therapy in Obsessive-Compulsive Disorder in a Randomized Controlled Trial 在一项随机对照试验中，症状激发时杏仁核激活的增加可预测强迫症患者对重复经颅磁刺激和暴露疗法的反应。

IF 5.7 2区医学 Q1 NEUROSCIENCES

Biological Psychiatry-Cognitive Neuroscience and Neuroimaging

Pub Date : 2025-03-01 DOI: 10.1016/j.bpsc.2024.10.020

Milan Houben , Tjardo S. Postma , Sophie M.D.D. Fitzsimmons , Chris Vriend , Neeltje M. Batelaan , Adriaan W. Hoogendoorn , Ysbrand D. van der Werf , Odile A. van den Heuvel

Background

Repetitive transcranial magnetic stimulation (rTMS) combined with exposure and response prevention is a promising treatment modality for treatment-refractory obsessive-compulsive disorder (OCD). However, not all patients respond sufficiently to this treatment. We investigated whether brain activation during a symptom provocation task could predict treatment response.

Methods

Sixty-one adults with OCD (39 female/22 male) underwent symptom provocation with OCD- and fear-related visual stimuli during functional magnetic resonance imaging prior to an 8-week combined rTMS and exposure and response prevention treatment regimen. Participants received one of the following 3 rTMS treatments as part of a randomized controlled trial: 1) 10-Hz rTMS (110% resting motor threshold) to the left dorsolateral prefrontal cortex, 2) 10-Hz rTMS (110% resting motor threshold) to the left presupplementary motor area, or 3) 10-Hz control rTMS (60% resting motor threshold) to the vertex. Multiple regression and correlation were used to examine the predictive value of task-related brain activation for treatment response in the following regions of interest: the dorsomedial prefrontal cortex, amygdala, dorsolateral prefrontal cortex, and left presupplementary motor area.

Results

The different treatment groups responded equally to treatment. Higher pretreatment task-related activation of the right amygdala to OCD-related stimuli showed a positive association with treatment response in all groups. Exploratory whole-brain analyses showed positive associations between activation in multiple task-relevant regions and treatment response. Only dorsal anterior cingulate cortex activation to fear-related stimuli showed a negative association with treatment outcome.

Conclusions

Higher pretreatment right amygdala activation during symptom provocation predicts better treatment response to combined rTMS and exposure and response prevention in OCD.

背景：重复经颅磁刺激（rTMS）与暴露和反应预防（ERP）相结合，是治疗难治性强迫症（OCD）的一种很有前景的治疗方式。然而，并非所有患者都对这种治疗方法有足够的反应。我们研究了在症状激惹任务中大脑激活是否能预测治疗反应：61名成人强迫症患者（22名男性/39名女性）在接受为期8周的经颅磁刺激和ERP联合治疗之前，在fMRI中接受了强迫症和恐惧相关视觉刺激的症状刺激。作为随机对照试验的一部分，参与者接受了以下三种经颅磁刺激治疗之一：（1）左侧背外侧前额叶皮层（DLPFC）10Hz经颅磁刺激（110%静息运动阈值（RMT））；（2）左侧前补充运动区（preSMA）10Hz经颅磁刺激（110% RMT）；或（3）顶点10Hz对照经颅磁刺激（60% RMT）。利用多元回归和相关性研究了任务相关脑激活对以下ROI的治疗反应的预测价值：背内侧前额叶皮层、杏仁核、DLPFC和preSMA：结果：不同治疗组对治疗的反应相同。在所有治疗组中，右侧杏仁核对强迫症相关刺激的较高治疗前任务相关激活与治疗反应呈正相关。探索性全脑分析显示，多个任务相关区域的激活与治疗反应呈正相关。只有背侧前扣带回皮层对恐惧相关刺激的激活与治疗结果呈负相关：结论：在症状激发时，治疗前较高的右杏仁核激活可预测强迫症患者对经颅磁刺激和ERP联合治疗的较好治疗反应。

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引用次数: 0

Challenges and Frontiers in Computational Metabolic Psychiatry 计算代谢精神病学的挑战与前沿。

IF 5.7 2区医学 Q1 NEUROSCIENCES

Biological Psychiatry-Cognitive Neuroscience and Neuroimaging

Pub Date : 2025-03-01 DOI: 10.1016/j.bpsc.2024.10.011

Anthony G. Chesebro , Botond B. Antal , Corey Weistuch , Lilianne R. Mujica-Parodi

One of the primary challenges in metabolic psychiatry is that the disrupted brain functions that underlie psychiatric conditions arise from a complex set of downstream and feedback processes that span multiple spatiotemporal scales. Importantly, the same circuit can have multiple points of failure, each of which results in a different type of dysregulation, and thus elicits distinct cascades downstream that produce divergent signs and symptoms. Here, we illustrate this challenge by examining how subtle differences in circuit perturbations can lead to divergent clinical outcomes. We also discuss how computational models can perform the spatially heterogeneous integration and bridge in vitro and in vivo paradigms. By leveraging recent methodological advances and tools, computational models can integrate relevant processes across scales (e.g., tricarboxylic acid cycle, ion channel, neural microassembly, whole-brain macrocircuit) and across physiological systems (e.g., neural, endocrine, immune, vascular), providing a framework that can unite these mechanistic processes in a manner that goes beyond the conceptual and descriptive to the quantitative and generative. These hold the potential to sharpen our intuitions toward circuit-based models for personalized diagnostics and treatment.

代谢精神病学面临的主要挑战之一是，导致精神疾病的大脑功能紊乱源于一系列复杂的下游和反馈过程，这些过程跨越多个时空尺度。重要的是，同一回路可能存在多个故障点，每个故障点都会导致不同类型的失调，从而引发不同的下游级联，产生不同的体征和症状。在这里，我们通过研究电路扰动的细微差别如何导致不同的临床结果来说明这一挑战。我们还讨论了计算模型如何进行空间异质整合，并在体外和体内范例之间架起桥梁。通过利用最新的方法学进展和工具，计算模型可以整合跨尺度（如 TCA 循环、离子通道、神经微组装、全脑宏电路）和跨生理系统（如神经、内分泌、免疫、血管）的相关过程，提供一个框架，以超越概念和描述的方式将这些机理过程结合起来，并进行定量和生成。这些都有可能使我们的直觉更加敏锐，从而建立基于电路的个性化诊断和治疗模型。

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引用次数: 0

An In Vivo Examination of the Relationship Between Metabotropic Glutamate 5 Receptor and Suicide Attempts in People With Borderline Personality Disorder 代谢性谷氨酸受体5与边缘型人格障碍患者自杀企图关系的体内研究。

IF 5.7 2区医学 Q1 NEUROSCIENCES

Biological Psychiatry-Cognitive Neuroscience and Neuroimaging

Pub Date : 2025-03-01 DOI: 10.1016/j.bpsc.2024.11.014

Margaret T. Davis , Ruth H. Asch , Emily R. Weiss , Ashley Wagner , Sarah K. Fineberg , Nabeel Nabulsi , David Matuskey , Richard E. Carson , Irina Esterlis

Background

Borderline personality disorder (BPD) is a serious psychiatric condition that is associated with a high risk for suicide attempts (SAs) and death by suicide. However, relatively little is known about the pathophysiology of BPD. The metabotropic glutamate 5 receptor (mGlu₅) has been specifically implicated in the pathophysiology of BPD and SAs, with more general roles in emotion regulation, social and cognitive functioning, and pain processing. Here, we examined the relationship between mGlu₅ availability, BPD, and SAs in vivo for the first time.

Methods

Eighteen individuals with BPD, 18 healthy control participants matched on age, sex, and smoking status, and 18 clinical comparison control participants with major depressive disorder completed comprehensive clinical assessments and participated in an [¹⁸F]FPEB positron emission tomography scan to measure mGlu₅ availability. The volume of distribution (V_T) in the frontolimbic circuit implicated in BPD pathophysiology was the positron emission tomography outcome measure.

Results

We observed significantly higher frontolimbic mGlu₅ availability in the BPD group than in both the healthy control group (p = .009, d = 0.84, 18.43% difference) and the major depressive disorder group (p = .03, d = 0.69, 15.21% difference). In the BPD, but not the major depressive disorder group, higher mGlu₅ availability was also associated with a history of SAs (19–25% higher, ps = .02–.005). Furthermore, mGlu₅ availability was positively correlated with risk factors for suicide (e.g., sexual victimization, perceived burdensomeness) in individuals with BPD and a history of SA.

Conclusions

Results show higher mGlu₅ availability in BPD and SA for the first time. Our preliminary findings suggest that mGlu₅ may be a critical treatment target for BPD symptoms, including SAs, and warrant additional investigation in larger samples.

背景：边缘型人格障碍（BPD）是一种严重的精神疾病，与自杀未遂和自杀死亡的高风险相关。然而，对BPD的病理生理机制知之甚少。代谢型谷氨酸受体5 （mGlu5）在BPD和自杀企图的病理生理中有特殊的作用，在情绪调节、社会和认知功能以及疼痛处理中也有更广泛的作用。在这里，我们首次在体内研究了mGlu5可用性、BPD和自杀企图之间的关系。方法：18名BPD患者、18名年龄、性别和吸烟状况匹配的健康（HC）患者和18名重度抑郁症（MDD）临床对照患者完成了全面的临床评估，并参与了[18F]FPEB正电子发射断层扫描（PET），以测量mGlu5的可用性。与BPD病理生理相关的额叶回路分布体积（VT）是PET的结果测量指标。结果：与两种HC相比，我们观察到BPD患者的额叶mGlu5有效性显著提高(p=。009, d=0.84，差异18.43%),MDD (p=。03, d=0.69，差异15.21%)。在BPD而非MDD组中，较高的mGlu5可用性也与自杀企图史相关(SA；高出19-25%，p's= 0.005 - 0.02)。此外，mGlu5可用性与BPD-SA组的自杀危险因素（如性受害、感知负担）呈正相关。结论：mGlu5在BPD和自杀企图中首次出现较高的可用性。我们的初步研究结果表明，mGlu5可能是BPD症状（包括自杀企图）的关键治疗靶点，值得在更大的样本中进一步研究。

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引用次数: 0

Editorial Board Page

IF 5.7 2区医学 Q1 NEUROSCIENCES

Biological Psychiatry-Cognitive Neuroscience and Neuroimaging

Pub Date : 2025-03-01 DOI: 10.1016/S2451-9022(25)00040-0

引用次数: 0

Intranasal Insulin Increases Brain Glutathione and Enhances Antioxidant Capacity in Healthy Participants but Not in Those With Early Psychotic Disorders 在健康参与者中，鼻内胰岛素增加脑谷胱甘肽（GSH）并增强抗氧化能力，但在早期精神病患者中没有。

IF 5.7 2区医学 Q1 NEUROSCIENCES

Biological Psychiatry-Cognitive Neuroscience and Neuroimaging

Pub Date : 2025-03-01 DOI: 10.1016/j.bpsc.2024.11.018

Virginie-Anne Chouinard , Wirya Feizi , Xi Chen , Boyu Ren , Kathryn E. Lewandowski , Jacey Anderson , Steven Prete , Emma Tusuzian , Kyle Cuklanz , Shuqin Zhou , Paula Bolton , Abigail Stein , Bruce M. Cohen , Fei Du , Dost Öngür

Background

We examined the acute effects of intranasal insulin on cognitive function and brain glutathione (GSH), a central factor in resistance to oxidative stress, in both participants with early psychosis and healthy control (HC) participants.

Methods

Twenty-one patients with early-stage psychotic disorders and 18 HC participants underwent magnetic resonance spectroscopy (MRS) scans and cognitive assessments before and after administration of intranasal insulin 40 IU. We conducted proton MRS (¹H-MRS) in the prefrontal cortex at 4T to measure GSH and glutamate metabolites. We assessed cognition using the Brief Assessment of Cognition in Schizophrenia symbol coding, digit sequencing, and verbal fluency tasks, in addition to the Stroop task.

Results

The mean (SD) age of participants was 25.7 (4.6) years; 51.3% were female. There were no significant group differences at baseline in age, sex, body mass index, homeostatic model assessment of insulin resistance (HOMA-IR), or cognition. Patients had higher baseline GSH (p < .001) and glutamate (p = .007). After insulin administration, GSH increased in HC participants (mean change, 0.15; 95% CI 0.03 to 0.26; p = .015), but not in patients. Symbol coding improved in both patients (0.74; 95% CI 0.37 to 1.11; p < .001) and HC participants (0.83; 95% CI 0.58 to 1.09; p < .001), and verbal fluency improved in HC participants (0.43; 95% CI 0.14 to 0.72; p = .006). Lower baseline HOMA-IR was associated with greater change in GSH (coefficient −0.22; 95% CI −0.40 to −0.04; p = .017).

Conclusions

Intranasal insulin increased brain GSH in HC participants, but not in patients with early psychotic disorders. These novel findings demonstrate that intranasal insulin enhances antioxidant capacity and resilience to oxidative stress in HC individuals in contrast to an absent antioxidant response in those with early psychotic disorders.

背景：我们研究了鼻内胰岛素对早期精神病患者和健康患者认知功能和脑谷胱甘肽（抗氧化应激的一个核心因素）的急性影响。方法：21例早期精神障碍患者和18名健康对照者在给予40 IU鼻内胰岛素前后进行磁共振波谱（MRS）扫描和认知评估。我们在4T时对前额皮质进行1h -磁共振波谱（MRS）检测谷胱甘肽（GSH）和谷氨酸代谢物。除了Stroop任务外，我们还使用了精神分裂症认知简要评估（BACS）符号编码、数字排序和语言流畅性任务来评估认知。结果：参与者的平均（SD）年龄为25.7岁（4.6岁）；51.3%为女性。在年龄、性别、体重指数、胰岛素抵抗稳态模型评估（HOMA-IR）或认知方面，基线组间无显著差异。患者有更高的基线谷胱甘肽(p)结论：鼻内胰岛素增加健康参与者的脑谷胱甘肽，但在早期精神障碍中没有。这些新发现表明，鼻内胰岛素可以增强健康个体的抗氧化能力和抗氧化应激能力，而早期精神病患者则没有抗氧化反应。

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引用次数: 0

Metabolic Status Modulates Global and Local Brain Age Estimates in Overweight and Obese Adults 代谢状态调节超重和肥胖成人的全球和局部脑年龄估计。

IF 5.7 2区医学 Q1 NEUROSCIENCES

Biological Psychiatry-Cognitive Neuroscience and Neuroimaging

Pub Date : 2025-03-01 DOI: 10.1016/j.bpsc.2024.11.017

Shalaila S. Haas , Fahim Abbasi , Kathleen Watson , Thalia Robakis , Alison Myoraku , Sophia Frangou , Natalie Rasgon

Background

As people live longer, maintaining brain health becomes essential for extending health span and preserving independence. Brain degeneration and cognitive decline are major contributors to disability. In this study, we investigated how metabolic health influences the brain age gap estimate (brainAGE), which measures the difference between neuroimaging-predicted brain age and chronological age.

Methods

K-means clustering was applied to fasting metabolic markers including insulin, glucose, leptin, cortisol, triglycerides, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol, steady-state plasma glucose, and body mass index of 114 physically and cognitively healthy adults. The homeostatic model assessment for insulin resistance served as a reference. T1-weighted brain magnetic resonance imaging was used to calculate voxel-level and global brainAGE. Longitudinal data were available for 53 participants over a 3-year interval.

Results

K-means clustering divided the sample into 2 groups, those with favorable (n = 58) and those with suboptimal (n = 56) metabolic health. The suboptimal group showed signs of insulin resistance and dyslipidemia (false discovery rate–corrected p < .05) and had older global brainAGE and local brainAGE, with deviations most prominent in cerebellar, ventromedial prefrontal, and medial temporal regions (familywise error–corrected p < .05). Longitudinal analysis revealed group differences but no significant time or interaction effects on brainAGE measures.

Conclusions

Suboptimal metabolic status is linked to accelerated brain aging, particularly in brain regions rich in insulin receptors. These findings highlight the importance of metabolic health in maintaining brain function and suggest that promoting metabolic well-being may help extend health span.

背景：随着人类寿命的延长，保持大脑健康对于延长健康寿命和保持独立性至关重要。大脑退化和认知能力下降是导致残疾的主要原因。这项研究调查了代谢健康如何影响脑年龄差距估计（brainAGE），它测量神经成像预测的脑年龄与实足年龄之间的差异。方法：采用k均值聚类方法对114名身体和认知健康成人的空腹代谢指标胰岛素、葡萄糖、瘦素、皮质醇、甘油三酯、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇、稳态血糖和体重指数进行分析。胰岛素抵抗的稳态模型评估作为参考。使用t1加权脑mri计算体素水平和全局（G-brainAGE）。对53名参与者进行了为期3年的纵向数据分析。结果：k均值聚类将样本分为两组：代谢健康良好（N=56）和次优（N=58）。亚优组表现出胰岛素抵抗和血脂异常的迹象（pfdrfwec）结论：亚优代谢状态与大脑加速衰老有关，特别是在富含胰岛素受体的大脑区域。这些发现强调了代谢健康对维持大脑功能的重要性，并表明促进代谢健康可能有助于延长健康寿命。

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引用次数: 0

Guide for Authors

IF 5.7 2区医学 Q1 NEUROSCIENCES

Biological Psychiatry-Cognitive Neuroscience and Neuroimaging

Pub Date : 2025-03-01 DOI: 10.1016/S2451-9022(25)00044-8

引用次数: 0

Metabolism Matters in Mental Health

IF 5.7 2区医学 Q1 NEUROSCIENCES

Biological Psychiatry-Cognitive Neuroscience and Neuroimaging

Pub Date : 2025-03-01 DOI: 10.1016/j.bpsc.2024.12.009

Zachary Freyberg , Judith M. Ford , Mary L. Phillips

引用次数: 0

Functional Connectivity Between Glutamate Receptor Antagonism and Insulin Pathways: Implications for Modeling Mechanism of Action of Ketamine/Esketamine and Dextromethorphan in Depression Treatment 谷氨酸受体拮抗与胰岛素通路之间的功能连接：氯胺酮/艾司他敏和右美沙芬在抑郁症治疗中的作用机制建模意义。

IF 5.7 2区医学 Q1 NEUROSCIENCES

Biological Psychiatry-Cognitive Neuroscience and Neuroimaging

Pub Date : 2025-03-01 DOI: 10.1016/j.bpsc.2024.10.004

Sabrina Wong , Gia Han Le , Rodrigo B. Mansur , Joshua D. Rosenblat , Roger S. McIntyre

引用次数: 0

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