The Molecular Organization of Consciousness

Self-awareness, an intricate aspect of human cognition, is intrinsically linked to the paralimbic network, a constellation of brain regions orchestrating conscious experience. This article examines the intricate relationship between empirical observations of consciousness and the theoretical frameworks that aim to comprehend it. It delves into the captivating hypothesis that the molecular mechanisms underlying self-awareness may provide a solution to bridge this gap and its relationship with the paralimbic network, dopamine, and GABAergic function. Recent research has illuminated the intricate molecular underpinnings of self-awareness, unveiling the pivotal roles of dopamine and GABA in the regulation of paralimbic activity. These novel findings suggest that dopamine plays a more profound role than previously thought in shaping conscious experiences. This indicates that dopamine not only regulates motivation and reward processing but also influences the fabric of our perception and awareness of the world.

The paralimbic network shows reduced binding of GABA in individuals with disorders such as autism and schizophrenia, which affects their self-awareness. On the other hand, addiction is linked to an increased release of dopamine in the network, suggesting that regulating dopamine levels in this network could be a potential therapeutic approach for treating these disorders. This opens avenues for research on how the paralimbic network influences cognitive functions beyond self-awareness, such as memory, decision-making, and attention. Furthermore, exploring the benefits of targeting neurotransmitters in the cortex to enhance GABA binding could improve self-awareness in individuals with developmental disorders, such as autism and addiction. Additionally, future studies should investigate neurotransmitters within the network and their interactions with dopamine and GABA. This would expand our understanding of how the paralimbic network contributes to other processes such as memory, decision making, and attention.

Introduction

Self-awareness, which refers to the ability to recognize and reflect on oneself, plays a role in thinking. This empowers us to navigate our surroundings, make informed choices, and establish connections. Although self-awareness is a phenomenon, scientists have discovered that the paralimbic network is crucial for its development and maintenance.

Self-awareness is an aspect of cognition closely tied to the paralimbic network. This network consists of interconnected hubs such as the prefrontal/anterior cingulate and medial parietal/posterior cingulate cortices. It is believed that this paralimbic default mode network serves as a coordinator for experiences by involving self-related processes and integrating information from both the external environment and introspective thoughts. Recent research has shed light on the relationship between dopamine and GABAergic function in the cortex, revealing an overlooked mechanism underlying conscious experience. Studies have shown that Dopamine, which is associated with reward and motivation, can influence GABA binding in the cortex, leading to improved perception and heightened awareness. Disruptions within this network have been linked to disorders characterized by impaired self-awareness and self-monitoring. Deficiencies in neurotransmission are particularly prevalent among these disorders. To explore the effects of dopamine on self-awareness, researchers have used a technique called stimulation (TMS) to specifically focus on the paralimbic hubs. The findings indicated that TMS application to these hubs impedes various aspects of self-awareness, with a latency of approximately 160 Ms. This network is dynamically interconnected via ∼40Hz oscillations and governed by dopamine.  (Lou1* 2020)

Dopamine and GABA: Molecular Orchestrators of Self-Awareness

A significant revelation has emerged because of the knowledge gathered through breakthrough research on how neurotransmitters affect functions. A groundbreaking study has emerged that provides evidence that the neurotransmitter dopamine has a direct influence on our conscious visual experience. This study used a randomized controlled approach. It has been shown that activating dopamine with pergolide increases both the confidence and accuracy in recognizing shown words. This suggests that dopamine plays a role in the regulation of confidence in perception. This study employed an observational design, in which participants were observed while undergoing a visual perception task. The researchers measured their subjective confidence in their visual perceptions along with their recognition accuracy for briefly presented words. 

They conducted an experiment to examine how increasing dopamine activation using pergolide, which targets the D1 and D2 receptors, affects participants’ confidence in recognizing words and their performance on a word recognition task. The participants were asked to rate their confidence in seeing words on a scale from 0 to 3, and their performance was measured by calculating the percentage of responses in the task. The p-values provided (p = 0.0018, p = 0.006, and p < 0.0001) indicate the likelihood of obtaining these results if the initial assumption is true. The results showed a relationship between activation and subjective confidence, suggesting that dopamine played a role in shaping the perceived certainty of visual experiences. This study provides insights into the connection between neurotransmitters and conscious perception, specifically highlighting how dopamine influences subjective confidence in visual experience. These findings have implications for the understanding of the mechanisms involved in consciousness. Could potentially lead to innovative therapeutic approaches, for conditions that affect visual perception confidence. (lou 2016)

Studies like  (H. C. Lou 2015) provide evidence that dopamine plays a role in conscious self-monitoring. Participants in the study were divided into two groups; one received a placebo and the other received a dopamine agonist. Using fMRI scans the researchers observed their brain activity while they engaged in a task that required them to be aware of their thoughts and emotions. The findings revealed that those who took the dopamine agonist showed activity in the prefrontal cortex, an area of the brain associated with self-awareness.

Unveiling the Neural Mechanisms of Self-Consciousness: The Paralimbic System, GABA, and Dopamine in the Context of COVID-19

When it comes to understanding self-awareness, the paralimbic system of the brain plays a role. This region acts as a hub, shaping how we perceive ourselves by integrating information from our surroundings and internal experience. GABA, a neurotransmitter, plays a role in this process by stabilizing activity and fostering a coherent sense of self. Additionally, dopamine, which is well known for its involvement in the reward and motivation processes, significantly contributes to self-awareness by being released within this system. This release stimulated feelings of self-worth and satisfaction. However, with the emergence of COVID 19 we have realized that these neural mechanisms are vulnerable to disruption. The binding of SARS CoV 2 to ACE2 receptors throws off the balance of GABAergic signaling within the body. This disruption negatively affects the system’s ability to maintain self-awareness. Moreover, this disruption extends beyond this region and affects the non-neuronal GABAergic pathways. Consequently, these disruptions contribute to the symptoms commonly observed along with gut dysbiosis issues, such as endothelial and metabolic dysfunctions experienced by individuals affected by COVID 19. Furthermore, it is important to note that viral infections caused by SARS COV 2 virus also contribute to the process of senescence through the signaling of ANG II and the formation of syncytia, which further exacerbates the downregulation of GABA. This serves as a defense mechanism against infections. Understanding the interactions between GABA, dopamine, and the paralimbic system is essential for developing interventions that effectively address conditions resulting from COVID and enhance self-awareness. These interventions may involve adjusting GABAergic and dopaminergic signaling using medications and implementing neurorehabilitation strategies, for resilience and recovery purposes. (Sfera A 2022)

Implications for Understanding Dysfunctional Consciousness, Developmental Disorders, and Addiction

The journey of self-awareness begins in infancy, when a rudimentary form of consciousness manifests through the establishment of eye contact between newborns and their mothers. Mirror recognition tests, in which infants are placed before a mirror with a spot marked on their forehead, have revealed that a positive response, an attempt to remove the spot on their head, usually occurs around the age of two. This milestone signifies the development of self-recognition and the ability to distinguish one’s body from the external world.

The paralimbic network, another key brain network involved in self-awareness, is active, specific, and causal. Gamma synchrony, which is a pattern of electrical activity in the brain, plays a crucial role in self-awareness. Gamma synchrony develops throughout infancy, childhood, and adolescence into adulthood, and is regulated by dopamine and other neurotransmitters via GABA interneurons. “Major derailments of this network and self-awareness occur in developmental disorders of conscious self-regulation like autism, attention deficit hyperactivity disorder (ADHD), and schizophrenia. (Moller, 2019) (H. C. Lou, Paradigm shift in consciousness research: the child’s self-awareness and abnormalities in autism, ADHD and schizophrenia 2011)
The study of self-awareness has undergone a paradigm shift, moving beyond correlations, to understand the causal mechanisms underlying the development of self-awareness. This shift opens new perspectives for understanding the neural mechanisms of the developing self and causal effects of disturbances in developmental disorders. Several studies have been performed to understand the potential link between dopamine, GABA release, and impaired self-control and self-awareness. The outcome of this goal could be the development of targeted pharmacological interventions for modulating specific brain networks, potentially leading to improved treatments for neurological and psychiatric disorders.

Dopamine was used in two studies. Both demonstrate the significant impact of dopamine on GABA neurotransmission in the brain; they differ in the source of dopamine and its effects on GABA release. Dopamine challenge appears to have a direct effect on the GABA system in the medial prefrontal and anterior cingulate areas of the human brain. The study design was a randomized, double-blind, cross-controlled trial using PET imaging to measure the effect of L-dopa/dopamine challenge on GABA receptor availability in the living human cerebral cortex. 

Dopamine levels exhibit an intriguing pattern in the realm of problem gambling, characterized by diminished dopamine synthesis and elevated dopamine metabolites. This paradoxical scenario, backed by evidence of heightened dopamine release in response to stimulants such as amphetamine, suggests a potential hyperdopaminergic state in problem gamblers. Dopaminergic activation of GABA neurotransmission is attenuated in problem gambling, as evidenced by reduced GABA-A receptor availability and the inverted effect of exogenous dopamine on GABA neurotransmission in the neocortex of individuals with problem gambling. A study was conducted to test the hypothesis that the regulation of the GABA-argic system by the dopaminergic system was attenuated in problem gamblers. This also raises the possibility that the GABA receptor molecule may be a target for the treatment of problem gambling.

This study used [11C] Ro15-4513 PET to detect changes in synaptic GABA levels after oral doses of L-dopa in a double-blind controlled study of male problem gamblers and age-matched healthy male controls. The key finding was that the dopaminergic activation of GABA release was significantly attenuated in the problem gambling group compared to the healthy control group, suggesting that dysfunctional dopamine regulation of GABA release may contribute to problem gambling and gambling disorders. (Moller 2019) The exploration of GABA receptor subtypes holds promise for identifying treatments for addictive disorders. GABA receptors, which play a role in communication, provide valuable insight into the nature of addiction. These receptors have a structure consisting of five protein complexes that form a channel, allowing the flow of chloride ions and resulting in signals that regulate brain activity. When GABA binds to this channel, it stabilizes the conformation that facilitates signal transmission. However, it is not GABA that can bind to these receptors; other molecules such as dopamine also have the potential to interact with them. In cases like gambling disorder this interaction between dopamine and GABA receptors can disrupt mechanisms, for self-monitoring and self-control ultimately leading to behaviors.
(Diaz 2012) (Kalivas 2005)

Conclusion

The paralimbic network plays a pivotal role in self-awareness and conscious experiences. By unraveling the molecular underpinnings of this network, we gained insights into the neural mechanisms underlying these fundamental aspects of human cognition. This knowledge could pave the way for novel treatments for disorders that impair self-awareness, such as autism, schizophrenia, and addiction. These findings provide a strong foundation for future research in this field. New research could explore the role of other neurotransmitters in the paralimbic network and their interactions with Dopamine and GABA. Additionally, research could examine the function of the paralimbic network in other cognitive functions beyond self-awareness, such as attention, decision-making, and memory. Finally, the potential therapeutic applications of targeting the paralimbic network should be further investigated.

Discussion

The complex interaction between dopamine and GABA as seen in studies like the one conducted by (H. C. Lou 2015) and (Joensson . (2015)) emphasize their roles in regulating self-awareness. (H. C. Lou 2015) showed that activating dopamine enhances self-monitoring by increasing activity in the prefrontal cortex. On the hand,  (Moller 2019) discovered that imbalances in dopamine and GABA levels can lead to self-control and increased inclination for risky behaviors particularly among individuals with gambling problems. These findings suggest that therapeutic interventions aimed at these neurotransmitters could be promising treatments for conditions associated with self-awareness.

For example, using dopamine agonists to raise dopamine levels in the brain could potentially alleviate symptoms of autism spectrum disorder (ASD). This approach might improve interaction and communication skills for individuals with ASD. Conversely reducing GABA levels in the brain using antagonists could potentially address symptoms of schizophrenia. This strategy might help reduce hallucinations, delusions, and disorganized thinking among individuals with schizophrenia.

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Lou, Hans C. 2011. “Paradigm shift in consciousness research: the child’s self-awareness and abnormalities in autism, ADHD and schizophrenia .” the journal Acta Paediatrica.P. 

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Lou1*, Hans C. 2020. “Molecular organization of self awarness paralimbic dopmaine gaba interaction.” front.Syst.Neurosci. 

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Moller, A., & Knutson, B. (2019). 3(1527). 2019. “Dopamine, GABA neurotransmission, and self-control in problem gambling: A neuropsychopharmacology perspective1.” .Frontiers in Neuroscience, . 

Sfera A, Thomas KG, Sasannia S, Anton JJ, Andronescu CV, Garcia M, Sfera DO, Cummings MA, Kozlakidis Z. 2022. ” Neuronal and non-neuronal GABA in COVID-19: Relevance for psychiatry.” Front Neurosci. 

Lou, H. C., et al. (2015). Dopamine activates conscious self-monitoring through medial prefrontal cortex. Human Brain Mapping, 36(7), 2272-2282 (H. C. Lou 2015)

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