ArticleBiological psychiatry2017
Hypofrontality and Posterior Hyperactivity in Early Schizophrenia: Imaging and Behavior in a Preclinical Model.
Article in Biological psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 30 citations in OpenAlex.
- Prefrontal Cortex Dysfunction as a Precipitating Factor for Schizophrenia and Depression.Journal of neurochemistry · 2026Review
- Investigating seasonal metabolic variations in bipolar disorder: a targeted metabolomics study.BMC psychiatry · 2025Article
- Differential impacts of social isolation and enriched environment on multi-sensory brain-wide functionality and network segregation.Nature communications · 2025Article
- Computational modeling of reversal learning impairments in schizophrenia and bipolar disorder reveals shared failure to exploit rewards.Journal of psychopathology and clinical science · 2025Article
- mTOR inhibition enhances synaptic and mitochondrial function in Alzheimer's disease in an APOE genotype-dependent manner.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Irregularity of visual motion perception and negative symptoms in schizophrenia.Schizophrenia (Heidelberg, Germany) · 2024Article
- Hub genes, a diagnostic model, and immune infiltration based on ferroptosis-linked genes in schizophrenia.IBRO neuroscience reports · 2024Article
- Resting State Brain Networks under Inverse Agonist versus Complete Knockout of the Cannabinoid Receptor 1.ACS chemical neuroscience · 2024Article
- GABAergic dysfunction in postmortem dorsolateral prefrontal cortex: implications for cognitive deficits in schizophrenia and affective disorders.Frontiers in cellular neuroscience · 2024Review
- Current Status of Our Understanding for Brain Integrated Functions and its Energetics.Neurochemical research · 2022Article
- Small loci of astroglial glutamine synthetase deficiency in the postnatal brain cause epileptic seizures and impaired functional connectivity.Epilepsia · 2021Article
- Frontal-posterior functional imbalance and aberrant function developmental patterns in schizophrenia.Translational psychiatry · 2021Article
- Early-Stage Repetitive Transcranial Magnetic Stimulation Altered Posterior-Anterior Cerebrum Effective Connectivity in Methylazoxymethanol Acetate Rats.Frontiers in neuroscience · 2021Article
- Kaempferol Treatment after Traumatic Brain Injury during Early Development Mitigates Brain Parenchymal Microstructure and Neural Functional Connectivity Deterioration at Adolescence.Journal of neurotrauma · 2020Article
- Quantitative Rodent Brain Receptor Imaging.Molecular imaging and biology · 2020Review
- Nicotine Self-administration Is Not Increased in the Methylazoxymethanol Acetate Rodent Model of Schizophrenia.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2020Article
- Nitric oxide, asymmetric dimethylarginine, symmetric dimethylarginine and L-arginine levels in psychotic exacerbation of schizophrenia and bipolar disorder manic episode.Saudi medical journal · 2020Article
- Influence of EGR3 Transfection on Imaging and Behavior in Rats and Therapeutic Effect of Risperidone in Schizophrenia Model.Frontiers in psychiatry · 2020Article
- Mapping Theme Trends and Knowledge Structure of Magnetic Resonance Imaging Studies of Schizophrenia: A Bibliometric Analysis From 2004 to 2018.Frontiers in psychiatry · 2020Article
- NMDA Receptor Model of Antipsychotic Drug-Induced Hypofrontality.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundSchizophrenia is a debilitating neuropsychiatric disorder typically diagnosed from late adolescence to adulthood. Subthreshold behavioral symptoms (e.g., cognitive deficits and substance abuse) often precede the clinical diagnosis of schizophrenia. However, these prodromal symptoms have not been consistently associated with structural and functional brain biomarkers, limiting the chance of early diagnosis of schizophrenia.
methodsUsing an extensively multimodal range of magnetic resonance methods (for anatomy, metabolism, and function), we screened early biomarkers in a methylazoxymethanol acetate (MAM) rat model of schizophrenia and saline-treated control (SHAM) rats, in conjunction with immunohistochemistry, myelin staining, and a novel three-choice, reversal-learning task to identify early behavioral markers corresponding the subthreshold symptoms.
resultsMAM (vs. SHAM) rats had lower/higher structural connectivity in anterior/posterior corpus callosum. The orbitofrontal cortex of MAM rats showed lower resting-state functional magnetic resonance imaging functional connectivity in conjunction with lower neuronal density, lower glucose oxidation, and attenuated neurotransmission (hypofrontality). In contrast, these measures were all higher in visual cortex of MAM rats (posterior hyperactivity), which might parallel perceptual problems in schizophrenia. In behavioral studies, MAM (vs. SHAM) rats displayed abnormal orbitofrontal cortex-mediated decision-making processes, resulting in a novel reward-sensitive hyperflexible phenotype, which might reflect vulnerability of prodromal patients to substance abuse.
conclusionsWe identified two novel biomarkers of early schizophrenia in a preclinical rat model: hypofrontality associated with the hyperflexible phenotype, and posterior hyperactivity. Because each of these magnetic resonance methods is clinically translatable, these markers could contribute to early diagnosis and the development of novel therapies of schizophrenia.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.