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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 -
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 -
The American Journal of Psychiatry Jul 2019The interpretability of results in psychiatric neuroimaging is significantly limited by an overreliance on correlational relationships. Purely correlational studies...
OBJECTIVE
The interpretability of results in psychiatric neuroimaging is significantly limited by an overreliance on correlational relationships. Purely correlational studies cannot alone determine whether behavior-imaging relationships are causal to illness, functionally compensatory processes, or purely epiphenomena. Negative symptoms (e.g., anhedonia, amotivation, and expressive deficits) are refractory to current medications and are among the foremost causes of disability in schizophrenia. The authors used a two-step approach in identifying and then empirically testing a brain network model of schizophrenia symptoms.
METHODS
In the first cohort (N=44), a data-driven resting-state functional connectivity analysis was used to identify a network with connectivity that corresponds to negative symptom severity. In the second cohort (N=11), this network connectivity was modulated with 5 days of twice-daily transcranial magnetic stimulation (TMS) to the cerebellar midline.
RESULTS
A breakdown of connectivity in a specific dorsolateral prefrontal cortex-to-cerebellum network directly corresponded to negative symptom severity. Restoration of network connectivity with TMS corresponded to amelioration of negative symptoms, showing a statistically significant strong relationship of negative symptom change in response to functional connectivity change.
CONCLUSIONS
These results demonstrate that a connectivity breakdown between the cerebellum and the right dorsolateral prefrontal cortex is associated with negative symptom severity and that correction of this breakdown ameliorates negative symptom severity, supporting a novel network hypothesis for medication-refractory negative symptoms and suggesting that network manipulation may establish causal relationships between network markers and clinical phenomena.
Topics: Cerebellum; Female; Humans; Male; Models, Biological; Nerve Net; Neuroimaging; Prefrontal Cortex; Psychiatric Status Rating Scales; Schizophrenia; Severity of Illness Index; Transcranial Magnetic Stimulation; Young Adult; beta-Lactamases
PubMed: 30696271
DOI: 10.1176/appi.ajp.2018.18040429 -
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 -
Neuropsychopharmacology : Official... Jan 2022Obsessive Compulsive Disorder (OCD) is a highly prevalent and severe neuropsychiatric disorder, with an incidence of 1.5-3% worldwide. However, despite the clear public... (Review)
Review
Obsessive Compulsive Disorder (OCD) is a highly prevalent and severe neuropsychiatric disorder, with an incidence of 1.5-3% worldwide. However, despite the clear public health burden of OCD and relatively well-defined symptom criteria, effective treatments are still limited, spotlighting the need for investigation of the neural substrates of the disorder. Human neuroimaging studies have consistently highlighted abnormal activity patterns in prefrontal cortex (PFC) regions and connected circuits in OCD during both symptom provocation and performance of neurocognitive tasks. Because of recent technical advances, these findings can now be leveraged to develop novel targeted interventions. Here we will highlight current theories regarding the role of the prefrontal cortex in the generation of OCD symptoms, discuss ways in which this knowledge can be used to improve treatments for this often disabling illness, and lay out challenges in the field for future study.
Topics: Humans; Magnetic Resonance Imaging; Neuroimaging; Obsessive-Compulsive Disorder; Prefrontal Cortex
PubMed: 34400778
DOI: 10.1038/s41386-021-01130-2 -
Advances in Clinical and Experimental... Mar 2022In the whole animal kingdom, fear learning is an essential process that allows living beings to survive. Therefore, revealing the neurophysiological processes that...
In the whole animal kingdom, fear learning is an essential process that allows living beings to survive. Therefore, revealing the neurophysiological processes that govern the expression of emotional fear memory and exploring its neurobiological underpinnings are the imperatives of affective neuroscience. Learned fear memories activate defensive behaviors in anticipation of harm, thus minimizing the impact of the threat. However, despite a century of research, the neural circuitry underlying fear learning in humans is still a matter of debate. This editorial will discuss recent evidence of the neural and behavioral correlates of fear learning in humans, with an emphasis on the role of the human prefrontal cortex (PFC).
Topics: Amygdala; Animals; Fear; Humans; Prefrontal Cortex
PubMed: 35195964
DOI: 10.17219/acem/146756 -
Nature May 2023Changes in patterns of activity within the medial prefrontal cortex enable rodents, non-human primates and humans to update their behaviour to adapt to changes in the...
Changes in patterns of activity within the medial prefrontal cortex enable rodents, non-human primates and humans to update their behaviour to adapt to changes in the environment-for example, during cognitive tasks. Parvalbumin-expressing inhibitory neurons in the medial prefrontal cortex are important for learning new strategies during a rule-shift task, but the circuit interactions that switch prefrontal network dynamics from maintaining to updating task-related patterns of activity remain unknown. Here we describe a mechanism that links parvalbumin-expressing neurons, a new callosal inhibitory connection, and changes in task representations. Whereas nonspecifically inhibiting all callosal projections does not prevent mice from learning rule shifts or disrupt the evolution of activity patterns, selectively inhibiting only callosal projections of parvalbumin-expressing neurons impairs rule-shift learning, desynchronizes the gamma-frequency activity that is necessary for learning and suppresses the reorganization of prefrontal activity patterns that normally accompanies rule-shift learning. This dissociation reveals how callosal parvalbumin-expressing projections switch the operating mode of prefrontal circuits from maintenance to updating by transmitting gamma synchrony and gating the ability of other callosal inputs to maintain previously established neural representations. Thus, callosal projections originating from parvalbumin-expressing neurons represent a key circuit locus for understanding and correcting the deficits in behavioural flexibility and gamma synchrony that have been implicated in schizophrenia and related conditions.
Topics: Animals; Mice; Learning; Neurons; Parvalbumins; Prefrontal Cortex; Neural Pathways; Schizophrenia; Corpus Callosum; Neural Inhibition
PubMed: 37100905
DOI: 10.1038/s41586-023-06012-9 -
The Neuroscientist : a Review Journal... Aug 2023Dysfunction in the prefrontal cortex is commonly implicated in anxiety disorders, but the mechanisms remain unclear. Approach-avoidance conflict tasks have been... (Review)
Review
Dysfunction in the prefrontal cortex is commonly implicated in anxiety disorders, but the mechanisms remain unclear. Approach-avoidance conflict tasks have been extensively used in animal research to better understand how changes in neural activity within the prefrontal cortex contribute to avoidance behaviors, which are believed to play a major role in the maintenance of anxiety disorders. In this article, we first review studies utilizing electrophysiology to reveal the relationship between changes in neural activity and avoidance behavior in rodents. We then review recent studies that take advantage of optical and genetic techniques to test the unique contribution of specific prefrontal cortex circuits and cell types to the control of anxiety-related avoidance behaviors. This new body of work reveals that behavior during approach-avoidance conflict is dynamically modulated by individual cell types, distinct neural pathways, and specific oscillatory frequencies. The integration of these different pathways, particularly as mediated by interactions between excitatory and inhibitory neurons, represents an exciting opportunity for the future of understanding anxiety.
Topics: Animals; Anxiety; Anxiety Disorders; Prefrontal Cortex; Avoidance Learning; Neural Pathways
PubMed: 35086369
DOI: 10.1177/10738584211069071 -
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