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Physiological Genomics Sep 2019The medial prefrontal cortex (mPFC) is a crucial cortical region that integrates information from numerous cortical and subcortical areas and converges updated... (Review)
Review
The medial prefrontal cortex (mPFC) is a crucial cortical region that integrates information from numerous cortical and subcortical areas and converges updated information to output structures. It plays essential roles in the cognitive process, regulation of emotion, motivation, and sociability. Dysfunction of the mPFC has been found in various neurological and psychiatric disorders, such as depression, anxiety disorders, schizophrenia, autism spectrum disorders, Alzheimer's disease, Parkinson's disease, and addiction. In the present review, we summarize the preclinical and clinical studies to illustrate the role of the mPFC in these neurological diseases.
Topics: Alzheimer Disease; Animals; Anxiety Disorders; Autism Spectrum Disorder; Depression; Humans; Parkinson Disease; Prefrontal Cortex; Schizophrenia; Substance-Related Disorders
PubMed: 31373533
DOI: 10.1152/physiolgenomics.00006.2019 -
Biological Psychiatry Apr 2018The ventromedial prefrontal cortex (vmPFC) has been implicated in a variety of social, cognitive, and affective functions that are commonly disrupted in mental illness.... (Review)
Review
The ventromedial prefrontal cortex (vmPFC) has been implicated in a variety of social, cognitive, and affective functions that are commonly disrupted in mental illness. In this review, we summarize data from a diverse array of human and animal studies demonstrating that the vmPFC is a key node of cortical and subcortical networks that subserve at least three broad domains of psychological function linked to psychopathology. One track of research indicates that the vmPFC is critical for the representation of reward- and value-based decision making, through interactions with the ventral striatum and amygdala. A second track of research demonstrates that the vmPFC is critical for the generation and regulation of negative emotion, through its interactions with the amygdala, bed nucleus of the stria terminalis, periaqueductal gray, hippocampus, and dorsal anterior cingulate cortex. A third track of research shows the importance of the vmPFC in multiple aspects of social cognition, such as facial emotion recognition, theory-of-mind ability, and processing self-relevant information, through its interactions with the posterior cingulate cortex, precuneus, dorsomedial PFC, and amygdala. We then present meta-analytic data revealing distinct subregions within the vmPFC that correspond to each of these three functions, as well as the associations between these subregions and specific psychiatric disorders (depression, posttraumatic stress disorder, addiction, social anxiety disorder, bipolar disorder, schizophrenia, and attention-deficit/hyperactivity disorder). We conclude by describing several translational possibilities for clinical studies of vmPFC-based circuits, including neuropsychological assessment of transdiagnostic functions, anatomical targets for intervention, predictors of treatment response, markers of treatment efficacy, and subtyping within disorders.
Topics: Animals; Decision Making; Emotions; Facial Recognition; Humans; Mental Disorders; Prefrontal Cortex; Reward; Social Perception; Theory of Mind
PubMed: 29275839
DOI: 10.1016/j.biopsych.2017.10.030 -
Neuron Jun 2021The prefrontal cortex (PFC) is considered to constitute the highest stage of neural integration and to be devoted to representation and production of actions. Studies in... (Review)
Review
The prefrontal cortex (PFC) is considered to constitute the highest stage of neural integration and to be devoted to representation and production of actions. Studies in primates have laid the foundation for theories regarding the principles of prefrontal function and provided mechanistic insights. The recent surge of studies of the PFC in mice holds promise for evolvement of present theories and development of novel concepts, particularly regarding principles shared across mammals. Here we review recent empirical work on the mouse PFC capitalizing on the experimental toolbox currently privileged to studies in this species. We conclude that this line of research has revealed cellular and structural distinctions of the PFC and neuronal activity with direct relevance to theories regarding the functions of the PFC. We foresee that data-rich mouse studies will be key to shed light on the general prefrontal architecture and mechanisms underlying cognitive aspects of organized actions.
Topics: Animals; Cognition; Electrophysiological Phenomena; Gene Expression Profiling; Mice; Models, Animal; Neural Pathways; Neurons; Prefrontal Cortex; Transcriptome
PubMed: 33894133
DOI: 10.1016/j.neuron.2021.03.035 -
Current Biology : CB Sep 2018The orbitofrontal cortex is a large and heterogeneous cortical area on the ventral surface of the frontal lobe and is intimately involved in emotion and executive...
The orbitofrontal cortex is a large and heterogeneous cortical area on the ventral surface of the frontal lobe and is intimately involved in emotion and executive function. In this Primer, Peter Rudebeck and Erin Rich summarize our understanding of the mechanisms through which orbitofrontal cortex adaptively shapes decision making and affective behavior.
Topics: Decision Making; Emotions; Humans; Prefrontal Cortex
PubMed: 30253144
DOI: 10.1016/j.cub.2018.07.018 -
NeuroImage Feb 2020Rumination is strongly and consistently correlated with depression. Although multiple studies have explored the neural correlates of rumination, findings have been... (Meta-Analysis)
Meta-Analysis Review
Rumination is strongly and consistently correlated with depression. Although multiple studies have explored the neural correlates of rumination, findings have been inconsistent and the mechanisms underlying rumination remain elusive. Functional brain imaging studies have identified areas in the default mode network (DMN) that appear to be critically involved in ruminative processes. However, a meta-analysis to synthesize the findings of brain regions underlying rumination is currently lacking. Here, we conducted a meta-analysis consisting of experimental tasks that investigate rumination by using Signed Differential Mapping of 14 fMRI studies comprising 286 healthy participants. Furthermore, rather than treat the DMN as a unitary network, we examined the contribution of three DMN subsystems to rumination. Results confirm the suspected association between rumination and DMN activation, specifically implicating the DMN core regions and the dorsal medial prefrontal cortex subsystem. Based on these findings, we suggest a hypothesis of how DMN regions support rumination and present the implications of this model for treating major depressive disorder characterized by rumination.
Topics: Brain Mapping; Depression; Humans; Nerve Net; Prefrontal Cortex; Rumination, Cognitive
PubMed: 31655111
DOI: 10.1016/j.neuroimage.2019.116287 -
Neuron Jan 2021Interactions between the thalamus and prefrontal cortex (PFC) play a critical role in cognitive function and arousal. Here, we use anatomical tracing, electrophysiology,...
Interactions between the thalamus and prefrontal cortex (PFC) play a critical role in cognitive function and arousal. Here, we use anatomical tracing, electrophysiology, optogenetics, and 2-photon Ca imaging to determine how ventromedial (VM) and mediodorsal (MD) thalamus target specific cell types and subcellular compartments in layer 1 (L1) of mouse PFC. We find thalamic inputs make distinct connections in L1, where VM engages neuron-derived neurotrophic factor (NDNF+) cells in L1a and MD drives vasoactive intestinal peptide (VIP+) cells in L1b. These separate populations of L1 interneurons participate in different inhibitory networks in superficial layers by targeting either parvalbumin (PV+) or somatostatin (SOM+) interneurons. NDNF+ cells also inhibit the apical dendrites of L5 pyramidal tract (PT) cells to suppress action potential (AP)-evoked Ca signals. Lastly, NDNF+ cells mediate a unique form of thalamus-evoked inhibition at PT cells, selectively blocking VM-evoked dendritic Ca spikes. Together, our findings reveal how two thalamic nuclei differentially communicate with the PFC through distinct L1 micro-circuits.
Topics: Animals; Female; Inhibitory Postsynaptic Potentials; Male; Mediodorsal Thalamic Nucleus; Mice; Mice, Inbred C57BL; Nerve Net; Optogenetics; Prefrontal Cortex
PubMed: 33188733
DOI: 10.1016/j.neuron.2020.10.031 -
International Review of Neurobiology 2021Across species, the medial prefrontal cortex guides actions in time. This process can be studied using behavioral paradigms such as simple reaction-time and... (Review)
Review
Across species, the medial prefrontal cortex guides actions in time. This process can be studied using behavioral paradigms such as simple reaction-time and interval-timing tasks. Temporal control of action can be influenced by prefrontal neurotransmitters such as dopamine and acetylcholine and is highly relevant to human diseases such as Parkinson's disease, schizophrenia, and attention-deficit hyperactivity disorder (ADHD). We review evidence that across species, medial prefrontal lesions impair the temporal control of action. We then consider neurophysiological correlates in humans, primates, and rodents that might encode temporal processing and relate to cognitive-control mechanisms. These data have informed brain-stimulation studies in rodents and humans that can compensate for timing deficits. This line of work illuminates basic mechanisms of temporal control of action in the medial prefrontal cortex, which underlies a range of high-level cognitive processing and could contribute to new biomarkers and therapies for human brain diseases.
Topics: Animals; Electronic Data Processing; Humans; Prefrontal Cortex; Primates; Rodentia; Time Factors
PubMed: 33785154
DOI: 10.1016/bs.irn.2020.11.004 -
Neuron Feb 2022In this issue of Neuron, Chiang et al. examine population coding of self-ordered sequences in prefrontal cortex. They find better decoding, more distributed...
In this issue of Neuron, Chiang et al. examine population coding of self-ordered sequences in prefrontal cortex. They find better decoding, more distributed information, and less variability when order is consistent. Consistent ordering produces reliable population response patterns that may aid planning and memory.
Topics: Neurons; Prefrontal Cortex
PubMed: 35176240
DOI: 10.1016/j.neuron.2022.01.022 -
Dialogues in Clinical Neuroscience Sep 2014Schizophrenia is a major psychiatric disorder that lacks a unifying neuropathology, while currently available pharmacological treatments provide only limited benefits to... (Review)
Review
Schizophrenia is a major psychiatric disorder that lacks a unifying neuropathology, while currently available pharmacological treatments provide only limited benefits to many patients. This review will discuss how the field of neuroepigenetics could contribute to advancements of the existing knowledge on the neurobiology and treatment of psychosis. Genome-scale mapping of DMA methylation, histone modifications and variants, and chromosomal loopings for promoter-enhancer interactions and other epigenetic determinants of genome organization and function are likely to provide important clues about mechanisms contributing to dysregulated expression of synaptic and metabolic genes in schizophrenia brain, including the potential links to the underlying genetic risk architecture and environmental exposures. In addition, studies in animal models are providing a rapidly increasing list of chromatin-regulatory mechanisms with significant effects on cognition and complex behaviors, thereby pointing to the therapeutic potential of epigenetic drug targets in the nervous system.
Topics: Animals; Epigenesis, Genetic; Epigenomics; Humans; Prefrontal Cortex; Schizophrenia
PubMed: 25364289
DOI: 10.31887/DCNS.2014.16.3/sakbarian -
Frontiers in Neural Circuits 2020Stimulus information is maintained in working memory by action potentials that persist after the stimulus is no longer physically present. The prefrontal cortex is a... (Review)
Review
Stimulus information is maintained in working memory by action potentials that persist after the stimulus is no longer physically present. The prefrontal cortex is a critical brain area that maintains such persistent activity due to an intrinsic network with unique synaptic connectivity, NMDA receptors, and interneuron types. Persistent activity can be highly plastic depending on task demands but it also appears in naïve subjects, not trained or required to perform a task at all. Here, we review what aspects of persistent activity remain constant and what factors can modify it, focusing primarily on neurophysiological results from non-human primate studies. Changes in persistent activity are constrained by anatomical location, with more ventral and more anterior prefrontal areas exhibiting the greatest capacity for plasticity, as opposed to posterior and dorsal areas, which change relatively little with training. Learning to perform a cognitive task for the first time, further practicing the task, and switching between learned tasks can modify persistent activity. The ability of the prefrontal cortex to generate persistent activity also depends on age, with changes noted between adolescence, adulthood, and old age. Mean firing rates, variability and correlation of persistent discharges, but also time-varying firing rate dynamics are altered by these factors. Plastic changes in the strength of intrinsic network connections can be revealed by the analysis of synchronous spiking between neurons. These results are essential for understanding how the prefrontal cortex mediates working memory and intelligent behavior.
Topics: Action Potentials; Animals; Humans; Interneurons; Learning; Memory, Short-Term; Nerve Net; Neuronal Plasticity; Neurons; Prefrontal Cortex
PubMed: 32528254
DOI: 10.3389/fncir.2020.00015