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Decoding human brain evolution: Insights from genomics

Current Opinion in Neurobiology 2025年 92卷 103033-103033页

作者： Liu, Yuting Li, Mingli Segal, Ashlea Zhang, Menglei Sestan, Nenad Department of Neuroscience Yale School of Medicine New Haven 06520 CT United States Wu-Tsai Institute Yale University New Haven 06520 CT United States Departments of Comparative Medicine Genetics and Psychiatry Program in Cellular Neuroscience Neurodegeneration and Repair and Kavli Institute for Neuroscience Yale School of Medicine New Haven 06510 CT United States

The human brain has undergone remarkable structural and functional specializations compared to that of nonhuman primates (NHPs), underlying the advanced cognitive abilities unique to humans. However, the cellular and genetic basis driving these specializations remains largely unknown. Comparing humans to our closest living relatives, chimpanzee and other great apes, is essential for identifying truly human-specific features. Recent comparative studies with closely related NHPs at the single-cell resolution using multimodal genomic profiling, assisted with high-throughput functional screening have provided unprecedented insights into human-specific brain features and their genetic underpinnings. In this review, we synthesize the current knowledge of human brain evolution at cellular and molecular levels, emphasizing how genetic changes have shaped these adaptations. We also discuss the emerging opportunities presented by new technologies and comprehensive atlases for advancing our understanding of human brain evolution. © 2025 The Authors

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Somatic mosaicism and interneuron involvement in mTORopathies

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Trends in neurosciences 2025年第5期48卷 362-376页

作者： Jerow, Lilian G. Krueger, Darcy A. Gross, Christina Danzer, Steve C. Neuroscience Graduate Program University of Cincinnati Cincinnati OH United States Department of Anesthesia Cincinnati Children's Hospital Medical Center Cincinnati OH United States Division of Neurology Cincinnati Children's Hospital Medical Center Cincinnati OH United States Department of Pediatrics University of Cincinnati College of Medicine Cincinnati OH United States Department of Anesthesiology University of Cincinnati College of Medicine Cincinnati OH United States

Somatic mutations in genes regulating mechanistic target of rapamycin (mTOR) pathway signaling can cause epilepsy, autism, and cognitive dysfunction. Research has predominantly focused on mTOR regulation of excitatory neurons in these conditions;however, dysregulated mTOR signaling among interneurons may also be critical. In this review, we discuss clinical evidence for interneuron involvement, and potential mechanisms, known and hypothetical, by which interneurons might come to directly harbor pathogenic mutations. To understand how mTOR hyperactive interneurons might drive dysfunction, we review studies in which mTOR signaling has been selectively disrupted among interneurons and interneuron progenitors in mouse model systems. Complex cellular mosaicism and dual roles for mTOR (hyper)activation in mediating disease pathogenesis and homeostatic responses raise challenging questions for effective treatment of these disorders. © 2025 Elsevier Ltd

关键词： epilepsy focal cortical dysplasia parvalbumin somatostatin tuberous sclerosis complex

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Brief report: A proof of concept study of altered magnocellular responses in autism spectrum disorder as assessed by contrasts functions for reversing checkerboards

Research in Autism

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Research in Autism 2025年 123卷

作者： Natalie F. Leslie-Fournier Jeffrey J. Hutsler Program in Neuroscience University of Nevada Reno USA

Background Alterations to early visual processing in autism spectrum disorder (ASD) may impact cognitive abilities and could serve as a potential neuromarker before behavioral symptoms appear. Behavioral research has suggested that visual alterations are linked to abnormalities in the magnocellular pathway. Methods Visual-evoked potentials (VEPs) were used to investigate early visual processing in adolescents with ASD. Two different-sized checkerboards (1° and .25°) displayed at four contrast levels (.025, .05, .1, and .98) were presented to seven ASD and eight neurotypical (NT) male subjects, between the ages of 10 to 15 years old. Peak amplitude and latency from the two earliest components—the N75 and P100–were analyzed. Results N75 amplitudes were largest at the highest contrast levels for both the small and large check sizes and did not differ according to diagnosis. For the P100, the ASD group consistently showed larger amplitudes than the NT subjects (p = .035), but there were no significant main effects or interactions involving diagnosis. Still, large effect sizes were found between ASD and NT subjects (d =.79–1.2) at the largest check size presented at lower contrast values. Latency differences between the subject groups were nonsignificant. Conclusions Group differences were most apparent at lower contrasts and large check sizes, pointing to a potential problem with early visual processing in the magnocellular pathway. Although additional research and a larger sample size is needed to confirm these findings, simple sensory measures may be useful as an indicator of ASD risk before the appearance of behavioral symptoms.

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Orderly specification and precise laminar deployment of mouse cortical projection neuron types through intermediate progenitors

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Developmental Cell 2025年

作者： Huilgol, Dhananjay Levine, Jesse M. Galbavy, William Wang, Bor-Shuen Huang, Z. Josh Department of Neurobiology Duke University Medical Center Durham NC United States Department of Biomedical Engineering Duke University Durham NC United States Cold Spring Harbor Laboratory Cold Spring Harbor NY United States Program in Neuroscience and Medical Scientist Training Program Stony Brook University Stony Brook NY United States Program in Neuroscience Department of Neurobiology and Behavior Stony Brook University Stony Brook NY United States

The cerebral cortex comprises diverse types of glutamatergic projection neurons (PNs) generated from radial glial progenitors (RGs) through either direct neurogenesis (dNG) or indirect neurogenesis (iNG) via intermediate progenitors (IPs). A foundational concept in corticogenesis is the “inside-out” model, whereby successive generations of PNs sequentially migrate first to deep and then progressively to more superficial layers. However, its biological significance remains unclear, and the role of iNG in this process is unknown. Using genetic strategies linking PN birth dating to projection mapping in mice, we found that the laminar deployment of IP-derived PNs substantially deviates from a stringent inside-out rule: PNs destined to non-consecutive layers are generated at the same time, and different PN types of the same layer are generated at non-contiguous times. The overarching scheme of iNG is the sequential specification and precise laminar deployment of projection-defined PN types, which may contribute to the orderly assembly of cortical output channels and processing streams. © 2025 Elsevier Inc.

关键词： fate mapping indirect neurogenesis intermediate progenitors neocortex projection neurons

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BPS2025 - Tyrosine kinase-dependent suppression of Kv1.2 containing channels by amyloid β(1-42) peptide: Critical role of Y132

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Biophysical Journal 2025年第3期124卷 130a-130a页

作者： Joseph Farley Dina Jamshidi Program in Neuroscience Indiana University Bloomington IN USA

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Did you say brain or brave? event-related potentials reveal the central role of phonological prediction in false hearing

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Brain and Language 2025年 267卷 105580页

作者： Silcox, Jack W Payne, Brennan R. Department of Psychology University of Utah United States Department of Communication Sciences and Disorders University of Utah United States Interdepartmental Neuroscience Program University of Utah United States

In the current paper, we report the results from two event-related brain potential (ERP) experiments that examined the time-course of false hearing (i.e., hearing one word when a different one was presented). Target words were presented in background noise whereas the preceding context (either a semantic prime word or a constraining sentence) was not. Participants routinely experienced false hearing, reporting a predictable word when an incongruent, phonological lure was presented. We found that the N400 to falsely heard words was similar to when a predictable word was presented even though a phonological lure was presented. Additionally, the N400 response to correctly identified phonological lures was significantly delayed compared to the response to incongruent words that shared no phonological relation to predictable words, suggesting the listeners engaged in phonological prediction. Altogether, the findings from the current study provide evidence that listeners’ engagement in phonological prediction can lead to misperception. © 2025 Elsevier Inc.

关键词： ERPs False hearing Language prediction Language/speech N400

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Focal control of non-invasive deep brain stimulation using multipolar temporal interference

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Bioelectronic Medicine 2025年第1期11卷 1-15页

作者： Botzanowski, Boris Acerbo, Emma Lehmann, Sebastian Kearsley, Sarah L. Steiner, Melanie Neufeld, Esra Missey, Florian Muller, Lyle Jirsa, Viktor Corneil, Brian D. Williamson, Adam UMR_1106 INSERM Aix-Marseille Université Marseille France St. Anne’S University Hospital Brno Czech Republic Department of Physiology and Pharmacology Western University LondonONN6A 5B7 Canada Graduate Program in Neuroscience Western University LondonONN6A 5B7 Canada IT’IS Foundation for Research on Information Technologies in Society Zurich8004 Switzerland Department of Mathematics Western University LondonONN6A 5B7 Canada Department of Psychology Western University LondonONN6A 5B7 Canada Robarts Research Institute Western University LondonONN6A 5B7 Canada Center for Social and Affective Neuroscience Department of Biomedical and Clinical Sciences Linköping University Linköping Sweden

Temporal interference (TI) is a method of non-invasive brain stimulation using transcutaneous electrodes which allows the targeting and modulation of deeper brain structures, not normally associated with non-invasive simulation, while avoiding unwanted stimulation of shallower cortical structures. The properties of TI have been previously demonstrated, however, the problem of decoupling stimulation focality from stimulation intensity has not yet been well addressed. In this paper, we provide a possible novel solution, multipolar TI (mTI), which allows increased independent control over both the size of the stimulated region and the stimulation intensity. The mTI method uses multiple carrier frequencies to create multiple overlapping amplitude-modulated envelopes, rather than using one envelope as in standard TI. The study presents an explanation of the concept of mTI along with experimental data gathered from Rhesus macaques and mice. We improved the focality at depth in anesthetized mice and monkeys, and using the new focality in awake monkeys, evoked targeted activity at depth in the superior colliculus. The mTI method could be an interesting and potentially useful new tool alongside other forms of non-invasive brain stimulation. Teaser Multipolar Temporal Interference Stimulation can produce a more focal brain stimulation at depth compared to Temporal Interference. © The Author(s) 2025.

关键词： Electric fields

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Adolescent Cannabis Use: It’s Safe Right?

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Current Treatment Options in Psychiatry 2025年第1期12卷 1-10页

作者： Rahat, Maryam Hopkinson, Paige McQuay, Sarah Patterson, Beth Rahat, Masoumeh Van Ameringen, Michael McMaster University Neuroscience Graduate Program Hamilton ON Canada MacAnxiety Research Centre Hamilton Hamilton ON Canada Royal College of Surgeons in Ireland Dublin Ireland Department of Psychiatry and Behavioural Neurosciences McMaster University Hamilton Canada Australian University of Kuwait West Mishref Kuwait Micheal G. DeGroote Centre for Medicinal Cannabis Research McMaster University Hamilton Canada David Boris Centre for Addictions Research McMaster University Hamilton Canada

Purpose of the review: Cannabis is one of the most commonly used psycho-active substances in the world. It has been used for medicinal and recreational purposes, with use frequently initiated during adolescence. Although once thought to be harmless, a growing body of evidence has associated adolescent cannabis use with adverse outcomes. A comprehensive literature review was conducted including cross-sectional and prospective studies examining the risk factors and potential impact of adolescent cannabis use. Recent findings: The findings of this review indicated that demographic variables such as age, male sex, and low socioeconomic status may predict the initiation of cannabis use during adolescence, as well as symptoms of anxiety and depression, impulsivity, and cannabis use of other family members and friends. Adverse consequences of adolescent cannabis use include depression, psychosis, suicidality, as well as negative impacts on overall functioning, cognition, and educational achievement. Summary: Although this area of research continues to be affected by numerous methodological limitations, there is strong evidence indicating a myriad of potential harms associated with the use of cannabis during adolescence. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2024.

关键词： Adolescence Adolescent Cannabis use Cannabis Use

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Alterations in Prefrontal Cortical Somatostatin Neurons in Schizophrenia: Evidence for Weaker Inhibition of Pyramidal Neuron Dendrites

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Biological Psychiatry 2025年

作者： Dienel, Samuel J. Wade, Kirsten L. Fish, Kenneth N. Lewis, David A. Translational Neuroscience Program Department of Psychiatry School of Medicine University of Pittsburgh Pittsburgh PA United States Department of Neuroscience Dietrich School of Arts and Sciences University of Pittsburgh Pittsburgh PA United States Center for the Neural Basis of Cognition Carnegie Mellon University Pittsburgh PA United States

Background: Certain cognitive processes require inhibition provided by the somatostatin (SST) class of GABA (gamma-aminobutyric acid) neurons in the dorsolateral prefrontal cortex (DLPFC). This inhibition onto pyramidal neuron dendrites depends on both SST and GABA signaling. Although SST messenger RNA (mRNA) levels are lower in the DLPFC in schizophrenia, it is not known whether SST neurons exhibit alterations in the capacity to synthesize GABA, principally via the 67-kilodalton isoform of glutamic acid decarboxylase (GAD67). Methods: GAD67 and SST mRNA levels were quantified in individual SST neurons using fluorescence in situ hybridization in DLPFC layers 2/superficial 3, where SST neurons are enriched, in individuals with schizophrenia (n = 46) and unaffected comparison (n = 46) individuals. Findings were compared with GAD67 and SST mRNA levels quantified by polymerase chain reaction and to final educational attainment, a proxy measure for cognitive functioning. Results: GAD67 (F_1,84 = 13.1, p = .0005, Cohen's d = −0.78) and SST (F_1,84 = 10.1, p = .002, Cohen's d = −0.64) mRNA levels in SST neurons were lower in schizophrenia, with no group differences in the relative density of SST neurons (F_1,84 = 0.21, p = .65). A presynaptic index of dendritic inhibition, derived by summing the alterations in GAD67 and SST mRNAs, was lower in 80.4% of individuals with schizophrenia and was associated with final educational attainment (adjusted odds ratio = 1.44, p = .022). Conclusions: Deficits in both GAD67 and SST mRNAs within SST neurons indicate that these neurons have a markedly reduced ability to inhibit postsynaptic pyramidal neuron dendrites in schizophrenia. These alterations likely contribute to cognitive dysfunction in schizophrenia. © 2025 Society of Biological Psychiatry

关键词： Cognition Fluorescence in situ hybridization Postmortem

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Diverging Effects of Violence Exposure and Psychiatric Symptoms on Amygdala-Prefrontal Maturation During Childhood and Adolescence

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Biological Psychiatry: Cognitive neuroscience and Neuroimaging 2025年第5期10卷 450-462页

作者： Keding, Taylor J. Russell, Justin D. Zhu, Xiaojin He, Quanfa Li, James J. Herringa, Ryan J. Neuroscience Training Program University of Wisconsin-Madison Madison WI United States Department of Psychiatry University of Wisconsin School of Medicine and Public Health Madison WI United States Department of Psychology Yale University New Haven Connecticut United States Department of Computer Science University of Wisconsin-Madison Madison WI United States Department of Psychology University of Wisconsin-Madison Madison WI United States Waisman Center University of Wisconsin-Madison Madison WI United States

Background: Violence exposure during childhood and adolescence is associated with increased prevalence and severity of psychopathology. Neurobiological correlates suggest that abnormal maturation of emotion-related brain circuitry, such as the amygdala-prefrontal cortex (PFC) circuit, may underlie the development of psychiatric symptoms after exposure. However, it remains unclear how amygdala-PFC circuit maturation is related to psychiatric risk in the context of violence. Methods: In this study, we analyzed individual differences in amygdala-PFC circuit maturity using data collected from the PNC (Philadelphia Neurodevelopmental Cohort) (n = 1133 youths). Neurodevelopment models of amygdala-PFC resting-state functional connectivity were built using deep learning and trained to predict chronological age in typically developing youths (not violence exposed and without a psychiatric diagnosis). Using the brain age gap estimate, an index of relative circuit maturation, patterns of atypical neurodevelopment were investigated. Results: Violence exposure was associated with delayed maturation of basolateral amygdala (BLA)–PFC circuits, driven by increased BLA–medial orbitofrontal cortex functional connectivity. In contrast, increased psychiatric symptoms were associated with advanced maturation of BLA-PFC functional connectivity, driven by decreased BLA–dorsolateral PFC functional connectivity. Conclusions: Delayed frontoamygdala maturation after exposure to violence suggests atypical, but adaptive, development of threat appraisal processes, potentially reflecting a greater threat generalization characteristic of younger children. Advanced circuit maturation with increasing symptoms suggests divergent neurodevelopmental mechanisms underlying illness after emotion circuits have adapted to adversity, exacerbated by preexisting vulnerabilities to early maturation. Disentangling the effects of adversity and psychopathology on neurodevelopment is crucial for helping youths reco

关键词： Amygdala Brain development Early-life adversity Machine learning Prefrontal cortex Violence

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