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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 -
Neuroscience Bulletin Apr 2015Schizophrenia is hypothesized to arise from disrupted brain connectivity. This "dysconnectivity hypothesis" has generated interest in discovering whether there is... (Review)
Review
Schizophrenia is hypothesized to arise from disrupted brain connectivity. This "dysconnectivity hypothesis" has generated interest in discovering whether there is anatomical and functional dysconnectivity between the prefrontal cortex (PFC) and other brain regions, and how this dysconnectivity is linked to the impaired cognitive functions and aberrant behaviors of schizophrenia. Critical advances in neuroimaging technologies, including diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI), make it possible to explore these issues. DTI affords the possibility to explore anatomical connectivity in the human brain in vivo and fMRI can be used to make inferences about functional connections between brain regions. In this review, we present major advances in the understanding of PFC anatomical and functional dysconnectivity and their implications in schizophrenia. We then briefly discuss future prospects that need to be explored in order to move beyond simple mapping of connectivity changes to elucidate the neuronal mechanisms underlying schizophrenia.
Topics: Animals; Diffusion Tensor Imaging; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Neural Pathways; Prefrontal Cortex; Schizophrenia
PubMed: 25761914
DOI: 10.1007/s12264-014-1502-8 -
Proceedings of the National Academy of... Oct 2012The prefrontal cortex (PFC) receives input from all other cortical regions and functions to plan and direct motor, cognitive, affective, and social behavior across time.... (Review)
Review
The prefrontal cortex (PFC) receives input from all other cortical regions and functions to plan and direct motor, cognitive, affective, and social behavior across time. It has a prolonged development, which allows the acquisition of complex cognitive abilities through experience but makes it susceptible to factors that can lead to abnormal functioning, which is often manifested in neuropsychiatric disorders. When the PFC is exposed to different environmental events during development, such as sensory stimuli, stress, drugs, hormones, and social experiences (including both parental and peer interactions), the developing PFC may develop in different ways. The goal of the current review is to illustrate how the circuitry of the developing PFC can be sculpted by a wide range of pre- and postnatal factors. We begin with an overview of prefrontal functioning and development, and we conclude with a consideration of how early experiences influence prefrontal development and behavior.
Topics: Animals; Biological Evolution; Child; Female; Humans; Life Change Events; Male; Neuronal Plasticity; Parent-Child Relations; Prefrontal Cortex; Pregnancy; Prenatal Exposure Delayed Effects; Psychotropic Drugs; Stress, Physiological
PubMed: 23045653
DOI: 10.1073/pnas.1121251109 -
Frontiers in Neural Circuits 2018Elucidating the prefrontal cortical microcircuit has been challenging, given its role in multiple complex behaviors, including working memory, cognitive flexibility,... (Review)
Review
Elucidating the prefrontal cortical microcircuit has been challenging, given its role in multiple complex behaviors, including working memory, cognitive flexibility, attention, social interaction and emotional regulation. Additionally, previous methodological limitations made it difficult to parse out the contribution of certain neuronal subpopulations in refining cortical representations. However, growing evidence supports a fundamental role of fast-spiking parvalbumin (PV) GABAergic interneurons in regulating pyramidal neuron activity to drive appropriate behavioral responses. Further, their function is heavily diminished in the prefrontal cortex (PFC) in numerous psychiatric diseases, including schizophrenia and autism. Previous research has demonstrated the importance of the optimal balance of excitation and inhibition (E/I) in cortical circuits in maintaining the efficiency of cortical information processing. Although we are still unraveling the mechanisms of information representation in the PFC, the E/I balance seems to be crucial, as pharmacological, chemogenetic and optogenetic approaches for disrupting E/I balance induce impairments in a range of PFC-dependent behaviors. In this review, we will explore two key hypotheses. First, PV interneurons are powerful regulators of E/I balance in the PFC, and help optimize the representation and processing of supramodal information in PFC. Second, diminishing the function of PV interneurons is sufficient to generate an elaborate symptom sequelae corresponding to those observed in a range of psychiatric diseases. Then, using this framework, we will speculate on whether this circuitry could represent a platform for the development of therapeutic interventions in disorders of PFC function.
Topics: Animals; Humans; Interneurons; Memory, Short-Term; Mental Disorders; Nerve Net; Prefrontal Cortex; Synaptic Transmission
PubMed: 29867371
DOI: 10.3389/fncir.2018.00037 -
International Review of Neurobiology 2010The prefrontal cortex occupies the anterior portion of the frontal lobes and is thought to be one of the most complex anatomical and functional structures of the... (Review)
Review
The prefrontal cortex occupies the anterior portion of the frontal lobes and is thought to be one of the most complex anatomical and functional structures of the mammalian brain. Its major role is to integrate and interpret inputs from cortical and sub-cortical structures and use this information to develop purposeful responses that reflect both present and future circumstances. This includes both action-oriented sequences involved in obtaining rewards and inhibition of behaviors that pose undue risk or harm to the individual. Given the central role in initiating and regulating these often complex cognitive and behavioral responses, it is no surprise that alcohol has profound effects on the function of the prefrontal cortex. In this chapter, we review the basic anatomy and physiology of the prefrontal cortex and discuss what is known about the actions of alcohol on the function of this brain region. This includes a review of both the human and animal literature including information on the electrophysiological and behavioral effects that follow acute and chronic exposure to alcohol. The chapter concludes with a discussion of unanswered questions and areas needing further investigation.
Topics: Alcohols; Animals; Executive Function; Humans; Memory, Short-Term; Neurons; Neurotransmitter Agents; Prefrontal Cortex
PubMed: 20813246
DOI: 10.1016/S0074-7742(10)91009-X -
Scientific Reports Jan 2021The ventromedial and dorsolateral prefrontal cortex are two major prefrontal regions that usually interact in serving different cognitive functions. On the other hand,...
The ventromedial and dorsolateral prefrontal cortex are two major prefrontal regions that usually interact in serving different cognitive functions. On the other hand, these regions are also involved in cognitive processing of emotions but their contribution to emotional processing is not well-studied. In the present study, we investigated the role of these regions in three dimensions (valence, arousal and dominance) of emotional processing of stimuli via ratings of visual stimuli performed by the study participants on these dimensions. Twenty- two healthy adult participants (mean age 25.21 ± 3.84 years) were recruited and received anodal and sham transcranial direct current stimulation (tDCS) (1.5 mA, 15 min) over the dorsolateral prefrontal cortex (dlPFC) and and ventromedial prefrontal cortex (vmPFC) in three separate sessions with an at least 72-h interval. During stimulation, participants underwent an emotional task in each stimulation condition. The task included 100 visual stimuli and participants were asked to rate them with respect to valence, arousal, and dominance. Results show a significant effect of stimulation condition on different aspects of emotional processing. Specifically, anodal tDCS over the dlPFC significantly reduced valence attribution for positive pictures. In contrast, anodal tDCS over the vmPFC significantly reduced arousal ratings. Dominance ratings were not affected by the intervention. Our results suggest that the dlPFC is involved in control and regulation of valence of emotional experiences, while the vmPFC might be involved in the extinction of arousal caused by emotional stimuli. Our findings implicate dimension-specific processing of emotions by different prefrontal areas which has implications for disorders characterized by emotional disturbances such as anxiety or mood disorders.
Topics: Adult; Arousal; Cognition; Emotions; Female; Humans; Male; Prefrontal Cortex; Transcranial Direct Current Stimulation; Young Adult
PubMed: 33479323
DOI: 10.1038/s41598-021-81454-7 -
Annual Review of Neuroscience 2010Neuroscientists have often described cognition and emotion as separable processes implemented by different regions of the brain, such as the amygdala for emotion and the... (Review)
Review
Neuroscientists have often described cognition and emotion as separable processes implemented by different regions of the brain, such as the amygdala for emotion and the prefrontal cortex for cognition. In this framework, functional interactions between the amygdala and prefrontal cortex mediate emotional influences on cognitive processes such as decision-making, as well as the cognitive regulation of emotion. However, neurons in these structures often have entangled representations, whereby single neurons encode multiple cognitive and emotional variables. Here we review studies using anatomical, lesion, and neurophysiological approaches to investigate the representation and utilization of cognitive and emotional parameters. We propose that these mental state parameters are inextricably linked and represented in dynamic neural networks composed of interconnected prefrontal and limbic brain structures. Future theoretical and experimental work is required to understand how these mental state representations form and how shifts between mental states occur, a critical feature of adaptive cognitive and emotional behavior.
Topics: Amygdala; Cognition; Emotions; Mental Processes; Models, Neurological; Prefrontal Cortex
PubMed: 20331363
DOI: 10.1146/annurev.neuro.051508.135256 -
Neuroscience Mar 2017Anxiety often is studied as a stand-alone construct in laboratory models. But in the context of coping with real-life anxiety, its negative impacts extend beyond... (Review)
Review
Anxiety often is studied as a stand-alone construct in laboratory models. But in the context of coping with real-life anxiety, its negative impacts extend beyond aversive feelings and involve disruptions in ongoing goal-directed behaviors and cognitive functioning. Critical examples of cognitive constructs affected by anxiety are cognitive flexibility and decision making. In particular, anxiety impedes the ability to shift flexibly between strategies in response to changes in task demands, as well as the ability to maintain a strategy in the presence of distractors. The brain region most critically involved in behavioral flexibility is the prefrontal cortex (PFC), but little is known about how anxiety impacts PFC encoding of internal and external events that are critical for flexible behavior. Here we review animal and human neurophysiological and neuroimaging studies implicating PFC neural processing in anxiety-induced deficits in cognitive flexibility. We then suggest experimental and analytical approaches for future studies to gain a better mechanistic understanding of impaired cognitive inflexibility in anxiety and related disorders.
Topics: Animals; Anxiety; Cognition; Executive Function; Humans; Prefrontal Cortex
PubMed: 27316551
DOI: 10.1016/j.neuroscience.2016.06.013 -
Neural Networks : the Official Journal... Apr 2009Humans and animals often must choose between rewards that differ in their qualities, magnitudes, immediacy, and likelihood, and must estimate these multiple reward... (Review)
Review
Humans and animals often must choose between rewards that differ in their qualities, magnitudes, immediacy, and likelihood, and must estimate these multiple reward parameters from their experience. However, the neural basis for such complex decision making is not well understood. To understand the role of the primate prefrontal cortex in determining the subjective value of delayed or uncertain reward, we examined the activity of individual prefrontal neurons during an inter-temporal choice task and a computer-simulated competitive game. Consistent with the findings from previous studies in humans and other animals, the monkey's behaviors during inter-temporal choice were well accounted for by a hyperbolic discount function. In addition, the activity of many neurons in the lateral prefrontal cortex reflected the signals related to the magnitude and delay of the reward expected from a particular action, and often encoded the difference in temporally discounted values that predicted the animal's choice. During a computerized matching pennies game, the animals approximated the optimal strategy, known as Nash equilibrium, using a reinforcement learning algorithm. We also found that many neurons in the lateral prefrontal cortex conveyed the signals related to the animal's previous choices and their outcomes, suggesting that this cortical area might play an important role in forming associations between actions and their outcomes. These results show that the primate lateral prefrontal cortex plays a central role in estimating the values of alternative actions based on multiple sources of information.
Topics: Algorithms; Animals; Association Learning; Decision Making; Game Theory; Haplorhini; Learning; Nerve Net; Neurons; Prefrontal Cortex; Reinforcement, Psychology
PubMed: 19375276
DOI: 10.1016/j.neunet.2009.03.010 -
Philosophical Transactions of the Royal... Apr 2005A comparison of the architecture of the human prefrontal cortex with that of the macaque monkey showed a very similar architectonic organization in these two primate... (Review)
Review
A comparison of the architecture of the human prefrontal cortex with that of the macaque monkey showed a very similar architectonic organization in these two primate species. There is no doubt that the prefrontal cortical areas of the human brain have undergone considerable development, but it is equally clear that the basic architectonic organization is the same in the two species. Thus, a comparative approach to the study of the functional organization of the primate prefrontal cortex is more likely to reveal the essential aspects of the various complex control processes that are the domain of frontal function. The lateral frontal cortex appears to be functionally organized along both a rostral-caudal axis and a dorsal-ventral axis. The most caudal frontal region, the motor region on the precentral gyrus, is involved in fine motor control and direct sensorimotor mappings, whereas the caudal lateral prefrontal region is involved in higher order control processes that regulate the selection among multiple competing responses and stimuli based on conditional operations. Further rostrally, the mid-lateral prefrontal region plays an even more abstract role in cognitive control. The mid-lateral prefrontal region is itself organized along a dorsal-ventral axis of organization, with the mid-dorsolateral prefrontal cortex being involved in the monitoring of information in working memory and the mid-ventrolateral prefrontal region being involved in active judgments on information held in posterior cortical association regions that are necessary for active retrieval and encoding of information.
Topics: Anatomy, Comparative; Animals; Brain Mapping; Cognition; Humans; Macaca; Memory; Physiology, Comparative; Prefrontal Cortex; Psychomotor Performance
PubMed: 15937012
DOI: 10.1098/rstb.2005.1631