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Current Neuropharmacology 2021Borderline Personality Disorder (BPD) is a chronic debilitating psychiatric disorder characterized mainly by emotional instability, chaotic interpersonal relationships,... (Review)
Review
Borderline Personality Disorder (BPD) is a chronic debilitating psychiatric disorder characterized mainly by emotional instability, chaotic interpersonal relationships, cognitive disturbance (e.g., dissociation and suicidal thoughts) and maladaptive behaviors. BPD has a high rate of comorbidity with other mental disorders and a high burden on society. In this review, we focused on two compromised brain regions in BPD - the hypothalamus and the corticolimbic system, emphasizing the involvement and potential contribution of the endocannabinoid system (ECS) to improvement in symptoms and coping. The hypothalamus-regulated endocrine axes (hypothalamic pituitary - gonadal, thyroid & adrenal) have been found to be dysregulated in BPD. There is also substantial evidence for limbic system structural and functional changes in BPD, especially in the amygdala and hippocampus, including cortical regions within the corticolimbic system. Extensive expression of CB1 and CB2 receptors of the ECS has been found in limbic regions and the hypothalamus. This opens new windows of opportunity for treatment with cannabinoids such as cannabidiol (CBD) as no other pharmacological treatment has shown long-lasting improvement in the BPD population to date. This review aims to show the potential role of the ECS in BPD patients through their most affected brain regions, the hypothalamus and the corticolimbic system. The literature reviewed does not allow for general indications of treatment with CBD in BPD. However, there is enough knowledge to indicate a treatment ratio of a high level of CBD to a low level of THC. A randomized controlled trial investigating the efficacy of cannabinoid based treatments in BPD is warranted.
Topics: Borderline Personality Disorder; Brain; Endocannabinoids; Humans; Hypothalamus; Limbic System
PubMed: 32351183
DOI: 10.2174/1570159X18666200429234430 -
Handbook of Clinical Neurology 2014Chronic use of alcohol results in progressive changes to brain and behavior that often lead to the development of alcohol dependence and alcoholism. Although the... (Review)
Review
Chronic use of alcohol results in progressive changes to brain and behavior that often lead to the development of alcohol dependence and alcoholism. Although the mechanisms underlying the development of alcoholism remain to be fully elucidated, diminished executive functioning due to hypoactive prefrontal cortex executive control and hyperactive limbic system anxiety and negative emotion might contribute mechanistically to the shift from experimental use to alcoholism and dependence. In the chapter that follows, behavioral deficits associated with cortical dysfunction and neurodegeneration will be related to the behavioral characteristics of alcoholism (e.g., diminished executive function, impulsivity, altered limbic modulation). We will provide evidence that alterations in cyclic AMP-responsive element binding protein (CREB: neurotrophic) and NF-κB (neuroimmune) signaling contribute to the development and persistence of alcoholism. In addition, genetic predispositions and an earlier age of drinking onset will be discussed as contributing factors to the development of alcohol dependence and alcoholism. Overall chronic ethanol-induced neuroimmune gene induction is proposed to alter limbic and frontal neuronal networks contributing to the development and persistence of alcoholism.
Topics: Alcoholism; Animals; Anxiety; Brain; Executive Function; Humans; Inflammation Mediators; Limbic System; Prefrontal Cortex; Signal Transduction
PubMed: 25307591
DOI: 10.1016/B978-0-444-62619-6.00027-6 -
The Journal of Neuroscience : the... Sep 2023Stimulation-evoked signals are starting to be used as biomarkers to indicate the state and health of brain networks. The human limbic network, often targeted for brain...
Stimulation-evoked signals are starting to be used as biomarkers to indicate the state and health of brain networks. The human limbic network, often targeted for brain stimulation therapy, is involved in emotion and memory processing. Previous anatomic, neurophysiological, and functional studies suggest distinct subsystems within the limbic network (Rolls, 2015). Studies using intracranial electrical stimulation, however, have emphasized the similarities of the evoked waveforms across the limbic network. We test whether these subsystems have distinct stimulation-driven signatures. In eight patients (four male, four female) with drug-resistant epilepsy, we stimulated the limbic system with single-pulse electrical stimulation. Reliable corticocortical evoked potentials (CCEPs) were measured between hippocampus and the posterior cingulate cortex (PCC) and between the amygdala and the anterior cingulate cortex (ACC). However, the CCEP waveform in the PCC after hippocampal stimulation showed a unique and reliable morphology, which we term the "limbic Hippocampus-Anterior nucleus of the thalamus-Posterior cingulate, HAP-wave." This limbic HAP-wave was visually distinct and separately decoded from the CCEP waveform in ACC after amygdala stimulation. Diffusion MRI data show that the measured end points in the PCC overlap with the end points of the parolfactory cingulum bundle rather than the parahippocampal cingulum, suggesting that the limbic HAP-wave may travel through fornix, mammillary bodies, and the anterior nucleus of the thalamus (ANT). This was further confirmed by stimulating the ANT, which evoked the same limbic HAP-wave but with an earlier latency. Limbic subsystems have unique stimulation-evoked signatures that may be used in the future to help network pathology diagnosis. The limbic system is often compromised in diverse clinical conditions, such as epilepsy or Alzheimer's disease, and characterizing its typical circuit responses may provide diagnostic insight. Stimulation-evoked waveforms have been used in the motor system to diagnose circuit pathology. We translate this framework to limbic subsystems using human intracranial stereo EEG (sEEG) recordings that measure deeper brain areas. Our sEEG recordings describe a stimulation-evoked waveform characteristic to the memory and spatial subsystem of the limbic network that we term the "limbic HAP-wave." The limbic HAP-wave follows anatomic white matter pathways from hippocampus to thalamus to the posterior cingulum and shows promise as a distinct biomarker of signaling in the human brain memory and spatial limbic network.
Topics: Humans; Male; Female; Limbic System; Electroencephalography; Evoked Potentials; Epilepsy; Electric Stimulation; Anterior Thalamic Nuclei
PubMed: 37620159
DOI: 10.1523/JNEUROSCI.2201-22.2023 -
Schizophrenia Bulletin Jan 2008Studies of adults with schizophrenia provide converging evidence for abnormalities in the limbic system. Limbic structures that show consistent patient/control... (Review)
Review
Studies of adults with schizophrenia provide converging evidence for abnormalities in the limbic system. Limbic structures that show consistent patient/control differences in both postmortem and neuroimaging studies include the anterior cingulate and hippocampus, although differences in the amygdala, parahippocampal gyrus, and fornix have also been observed. Studies of white matter in children and adolescents with schizophrenia tend to show findings that are more focal than those seen in adults. Interestingly, these focal abnormalities in early-onset schizophrenia tend to be more localized to limbic regions. While it is unclear if these early limbic abnormalities are primary in the etiology of schizophrenia, there is evidence that supports a developmental progression with early limbic abnormalities evolving over time to match the neuroimaging profiles seen in adults with schizophrenia. Alternatively, the aberrations in limbic structures may be secondary to a more widespread or global pathological processes occurring with the brain that disrupt neural transmission. The goal of this article is to provide a review of the limbic system and limbic network abnormalities reported in children and adolescents with schizophrenia. These findings are compared with the adult literature and placed within a developmental context. These observations from neuroimaging studies enrich our current understanding of the neurodevelopmental model of schizophrenia and raise further questions about primary vs secondary processes. Additional research within a developmental framework is necessary to determine the putative etiologic roles for limbic and other brain abnormalities in early-onset schizophrenia.
Topics: Adolescent; Brain; Child; Humans; Limbic System; Magnetic Resonance Imaging; Nerve Net; Schizophrenia
PubMed: 17942479
DOI: 10.1093/schbul/sbm110 -
PloS One 2017Volume loss in some limbic region structures has been observed in multiple sclerosis (MS) patients. However, in vivo evaluation of existing tissue cellular...
Volume loss in some limbic region structures has been observed in multiple sclerosis (MS) patients. However, in vivo evaluation of existing tissue cellular microstructure integrity has received less attention. The goal of studies reported here was to quantitatively assess loss of limbic system volumes and tissue integrity, and to evaluate associations of these measures with cognitive and physical dysfunction in MS patients. Thirty-one healthy controls (HC) and 80 MS patients, including 32 relapsing remitting (RRMS), 32 secondary progressive (SPMS) and 16 primary progressive (PPMS), participated in this study. Tissue cellular integrity was evaluated by means of recently introduced tissue-specific parameter R2t* that was calculated from multi-gradient-echo MRI signals using a recently developed method that separates R2t* from BOLD (blood oxygen level dependent) contributions to GRE signal decay rate constant (R2*), and accounting for physiological fluctuations and artifacts from background gradients. Volumes in limbic system regions, normalized to skull size (NV), were measured from standard MPRAGE images. MS patients had lower R2t* and smaller normalized volumes in the hippocampus, amygdala, and several other limbic system regions, compared to HC. Alterations in R2t* of several limbic system regions correlated with clinical and neurocognitive test scores in MS patients. In contrast, smaller normalized volumes in MS were only correlated with neurocognitive test scores in the hippocampus and amygdala. This study reports the novel finding that R2t*, a measure that estimates tissue integrity, is more sensitive to tissue damage in limbic system structures than is atrophy. R2t* measurements can serve as a biomarker that is distinct from and complementary to volume measurements.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Limbic System; Magnetic Resonance Imaging; Male; Middle Aged; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Neuropsychological Tests; Organ Size
PubMed: 29121642
DOI: 10.1371/journal.pone.0187915 -
Scientific Reports Jul 2020The limbic system is a phylogenetically old, behaviorally defined system that serves as a center for emotions. It controls the expression of anger, fear, and joy and...
The limbic system is a phylogenetically old, behaviorally defined system that serves as a center for emotions. It controls the expression of anger, fear, and joy and also influences sexual behavior, vegetative functions, and memory. The system comprises a collection of tel-, di-, and mesencephalic structures whose components have evolved and increased over time. Previous animal research indicates that the anterior nuclear group of the thalamus (ANT), as well as the habenula (Hb) and the adjacent mediodorsal nucleus (MD) each play a vital role in the limbic circuitry. Accordingly, diffusion imaging data of 730 subjects obtained from the Human Connectome Project and the masks of six nuclei (anterodorsal, anteromedial, anteroventral, lateral dorsal, Hb, and MD) served as seed regions for a direct probabilistic tracking to the rest of the brain using diffusion-weighted imaging. The results revealed that the ANT nuclei are part of the limbic and the memory system as they mainly connect via the mammillary tract, mammillary body, anterior commissure, fornix, and retrosplenial cortices to the hippocampus, amygdala, medio-temporal, orbito-frontal and occipital cortices. Furthermore, the ANT nuclei showed connections to the mesencephalon and brainstem to varying extents, a pattern rarely described in experimental findings. The habenula-usually defined as part of the epithalamus-was closely connected to the tectum opticum and seems to serve as a neuroanatomical hub between the visual and the limbic system, brainstem, and cerebellum. Finally, in contrast to experimental findings with tracer studies, directly determined connections of MD were mainly confined to the brainstem, while indirect MD fibers form a broad pathway connecting the hippocampus and medio-temporal areas with the mediofrontal cortex.
Topics: Adult; Anterior Thalamic Nuclei; Diffusion Magnetic Resonance Imaging; Female; Humans; Limbic System; Male; Mediodorsal Thalamic Nucleus; Neural Pathways; Young Adult
PubMed: 32616764
DOI: 10.1038/s41598-020-67770-4 -
Progress in Neurobiology Oct 2011GABA is the main inhibitory neurotransmitter in the adult forebrain, where it activates ionotropic type A and metabotropic type B receptors. Early studies have shown... (Review)
Review
GABA is the main inhibitory neurotransmitter in the adult forebrain, where it activates ionotropic type A and metabotropic type B receptors. Early studies have shown that GABA(A) receptor-mediated inhibition controls neuronal excitability and thus the occurrence of seizures. However, more complex, and at times unexpected, mechanisms of GABAergic signaling have been identified during epileptiform discharges over the last few years. Here, we will review experimental data that point at the paradoxical role played by GABA(A) receptor-mediated mechanisms in synchronizing neuronal networks, and in particular those of limbic structures such as the hippocampus, the entorhinal and perirhinal cortices, or the amygdala. After having summarized the fundamental characteristics of GABA(A) receptor-mediated mechanisms, we will analyze their role in the generation of network oscillations and their contribution to epileptiform synchronization. Whether and how GABA(A) receptors influence the interaction between limbic networks leading to ictogenesis will be also reviewed. Finally, we will consider the role of altered inhibition in the human epileptic brain along with the ability of GABA(A) receptor-mediated conductances to generate synchronous depolarizing events that may lead to ictogenesis in human epileptic disorders as well.
Topics: Animals; Cortical Synchronization; Epilepsy; GABAergic Neurons; Humans; Limbic System; Nerve Tissue Proteins; Receptors, GABA; gamma-Aminobutyric Acid
PubMed: 21802488
DOI: 10.1016/j.pneurobio.2011.07.003 -
Neurosurgery Clinics of North America Jan 2014Deep brain stimulation, a technique whereby electrodes are implanted into specific brain regions to modulate their activity, has been mainly used to treat movement... (Review)
Review
Deep brain stimulation, a technique whereby electrodes are implanted into specific brain regions to modulate their activity, has been mainly used to treat movement disorders. More recently this technique has been proposed for the treatment of drug addiction, posttraumatic stress disorder (PTSD), and dementia. The nucleus accumbens, amygdala, and hippocampus, central nuclei within the limbic system, have been studied as potential targets for neuromodulation for the treatment of drug addiction, PTSD, and dementia, respectively. As the scope of neuromodulation grows to include disorders of mood and thought, new ethical and philosophic challenges that require multidisciplinary discussion and cooperation are emerging.
Topics: Deep Brain Stimulation; Humans; Limbic System; Memory Disorders; Stress Disorders, Post-Traumatic; Substance-Related Disorders
PubMed: 24262905
DOI: 10.1016/j.nec.2013.08.004 -
Neuropsychopharmacology : Official... Jun 2016In order to thrive, animals must be able to recognize aversive and appetitive stimuli within the environment and subsequently initiate appropriate behavioral responses.... (Review)
Review
In order to thrive, animals must be able to recognize aversive and appetitive stimuli within the environment and subsequently initiate appropriate behavioral responses. This assignment of positive or negative valence to a stimulus is a key feature of emotional processing, the neural substrates of which have been a topic of study for several decades. Until recently, the result of this work has been the identification of specific brain regions, such as the basolateral amygdala (BLA) and nucleus accumbens (NAc), as important to valence encoding. The advent of modern tools in neuroscience has allowed further dissection of these regions to identify specific populations of neurons signaling the valence of environmental stimuli. In this review, we focus upon recent work examining the mechanisms of valence encoding, and provide a model for the systematic investigation of valence within anatomically-, genetically-, and functionally defined populations of neurons.
Topics: Animals; Emotions; Humans; Limbic System; Neurons; Reinforcement, Psychology
PubMed: 26647973
DOI: 10.1038/npp.2015.358 -
Journal of Psychiatry & Neuroscience :... Nov 2007Neurochemical, electrophysiological and behavioural evidence indicates that certain forms of goal-directed behaviours are mediated by complex and reciprocal interactions... (Review)
Review
Neurochemical, electrophysiological and behavioural evidence indicates that certain forms of goal-directed behaviours are mediated by complex and reciprocal interactions between limbic and dopamine (DA) inputs in the nucleus accumbens (NAc). Mesoaccumbens DA transmission appears to be compartmentalized; synaptic DA transmission is mediated by phasic burst firing of DA neurons, whereas extrasynaptic tonic DA levels are regulated by DA neuron population activity and limbic glutamatergic inputs to the NAc. DA release facilitated by limbic inputs and acting on D1 receptors can either potentiate or suppress neural activity driven by separate limbic inputs converging on the same postsynaptic NAc neurons. In turn, D1 receptors in the NAc mediate accuracy of search behaviour regulated by hippocampal-ventral striatal circuitries; D2 receptors appear to mediate motivational aspects of task performance. These findings suggest that dopaminergic modulation of limbic afferents to the NAc may be a cellular mechanism for input selection that governs the smooth coordination of behaviour by permitting information processed by one limbic region to temporarily exert control over the type and intensity of adaptive behavioural responses.
Topics: Adaptation, Physiological; Corpus Striatum; Dopamine; Humans; Limbic System; Nerve Net; Nucleus Accumbens; Signal Transduction
PubMed: 18043763
DOI: No ID Found