The complexity of the human brain has fascinated neurologists for centuries. Its involvement in several critical neurological functions and disease states makes the mesocortical pathway a region of particular interest. This article explores the complexities of the mesocortical pathway and its involvement in pathologies.
The mesocortical pathway is a major dopaminergic pathway that connects the ventral tegmentum to the dorsolateral prefrontal cortex. It facilitates these brain regions' primary and secondary functions, including executive function, social cognition, and dopaminergic transmission.
As the center of our perceptions, emotions, and thoughts, the brain continues to be the focus of groundbreaking research. In particular, the mesocortical pathway's role in brain function and neural pathology remains a partially complete puzzle to neurologists.
What Is The Mesocortical Pathway?
The mesocortical pathway is a neural pathway that connects the ventral tegmentum, a cluster of neurons in the midbrain, to the dorsolateral prefrontal cortex. This pathway is one of the four major pathways responsible for dopaminergic transmission.
The mesocortical pathway's involvement in dopaminergic transmission means that it is integral to understanding the pathology of several neural disease states. This involvement also means that the pathway is an important target for drug treatment. Altering dopamine levels in patients with abnormal neural pathway function has been shown to manage their psychoses successfully.
The mesocortical pathway contributes to the cognitive function of the dorsolateral prefrontal cortex, which includes its primary and secondary functions. The primary function of the dorsolateral prefrontal cortex is to facilitate executive functions, a set of processes that enable the cognitive control of behavior. Specifically, these functions include decision-making and working memory.
When we are faced with making complex moral and risky decisions, the dorsolateral prefrontal cortex is activated. This brain region helps us weigh the costs and benefits of different choices and triggers a preference for the fairest option to avoid the temptation to prioritize personal gain.
Likewise, the dorsolateral prefrontal cortex is responsible for the system that actively retains information in the brain, known as working memory. Amongst neurologists, there is an ongoing discussion surrounding the kind of information for which this region is responsible, namely, the mechanism for manipulating and monitoring data and visuospatial information.
The secondary functions of the dorsolateral prefrontal cortex include social cognition and dopaminergic transmission. Although it is not the most significant influence on social behavior, this region contributes to organizing perspectives, deducing the intentions of others, suppressing self-centeredness, and commitment in a relationship.
As the rest of our body develops, so do our brain regions. With maturation, the dorsolateral prefrontal cortex experiences an increase in dopaminergic transmission. Dopamine is a neurotransmitter that facilitates the function of working memory in the dorsolateral prefrontal cortex.
Interestingly, although the dorsolateral prefrontal cortex is not solely responsible for motivation, attention, and drive, it is often implicated in the dysfunction of these processes. Individuals with low levels of function in the dorsolateral prefrontal cortex are likelier to display less spontaneity, alertness, motivation, and interest.
As developmental changes can influence our executive function, it is also susceptible to damage from various pathologies. Neurologists and psychiatrists use neuropsychological tests such as the Stroop test and the Behavior Rating Inventory of Executive Function to assess an individual's executive function level.
The Mesocortical Pathway's Role In Addiction
The role of the mesocortical pathway in addiction can be explained by its involvement in dopaminergic transmission. Dopamine is a neurotransmitter that is a crucial component in the brain's reward systems. When we experience a pleasant experience, such as eating our favorite meal, having sex, or using an addictive substance, our brain responds to the stimulus by producing dopamine.
The ventral tegmental area, located in the midbrain, is the primary site of dopamine production. Once it is produced, the dopamine is transported along neural pathways, such as the mesocortical pathway, to other brain areas. Since the cortex is responsible for cognitive thought, activating the mesocortical pathway's role in response to pleasure is to bring about the conscious experience of reward.
Addictive substances, such as stimulants, opioids, alcohol, and nicotine, utilize mechanisms to increase dopaminergic transmission above normal levels significantly. Addictive substances alter dopamine transmission by changing the rate of cell firing, extensively binding to the reward-related receptors, or inhibiting the rate of dopamine clearance from the synaptic cleft.
Hyperactivity in the dopaminergic pathways for extended periods leads to substance addiction. Furthermore, this chronic hyperactivity is key in triggering the neurobiological changes associated with addiction. The body relies on elevated dopaminergic transmission to maintain euphoric feelings and is less sensitive to normal dopamine levels.
Furthermore, hyperactivity in the dopaminergic pathways causes the body to produce lower serotonin levels, a neurotransmitter associated with happiness. The low levels of serotonin result in disinterest in everyday activities, which an individual would typically have found enjoyable, and ultimately consistently result in depressed moods.
Changes in the prefrontal cortex function, the target area of the mesocortical dopamine pathway, may skew information processing and memory formation. These changes cause the addict to hyper-fixate on drug-related cues, such as social or environmental triggers.
Disorders Of The Mesocortical Pathway
As we mature, our brain's neural pathways continuously change and develop. Similarly, these pathways can be altered by environmental risks, genetic abnormalities, and disease states. Factors affecting the mesocortical pathway's function influence the brain's ability to perform executive functions, display social cognition, and facilitate dopamine transmission.
Several significant disease states arise partly or entirely from neurobiological abnormalities in the mesocortical pathway. These include attention deficit hyperactivity disorder, schizophrenia, and Parkinson's disease.
The Mesocortical Pathway's Role In ADHD
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental illness characterized by persistent, debilitating, and age-inappropriate levels of inattention, carelessness, hyperactivity, and impulsivity. Some people with ADHD also struggle with emotion regulation and exhibit executive dysfunction.
Although persons with ADHD have difficulty focusing on things they are not very interested in completing, they can often sustain an abnormally extended and intense concentration level for projects that they find engaging or rewarding, known as hyperfocus.
ADHD is frequently linked to various mental illnesses and substance abuse issues. When individuals with ADHD partake in extended use of addictive drugs, the neurobiological changes caused by such medications can worsen the severity of the individual's ADHD. Furthermore, these individuals tend to hyper-fixate more on drug-related cues than addicts without ADHD.
In most ADHD cases, the etiology remains unknown. Toxins and infections during pregnancy, as well as brain damage, may be contributors. Current theories of ADHD imply that it is linked to dysfunctional neurotransmitter systems in the brain, notably those involving dopamine and norepinephrine.
The dopamine and norepinephrine pathways, which begin in the ventral tegmental area and locus coeruleus, branch out to other brain parts. These regions regulate a wide range of cognitive functions. The prefrontal cortex and striatum dopamine and norepinephrine pathways are recognized to play a significant role in the pathophysiology of ADHD.
Previously, it was assumed that the increased number of dopamine transporters in patients with ADHD was related to pathophysiology. However, recent discoveries suggest that these patients are less responsive to the expected levels of dopamine. Therefore, the limited activity in the mesolimbic pathway impairs executive function, which manifests as the symptoms displayed by individuals with ADHD.
Executive functions are a series of cognitive processes that allow you to successfully pick and monitor activities that help you achieve your goals. Staying organized, time keeping, excessive procrastination, maintaining focus, paying attention, ignoring distractions, managing emotions, and remembering information are all affected by executive function deficiencies in ADHD patients.
Long-term memory appears unaffected in people with ADHD, while long-term recall deficiencies appear to be caused by problems with working memory. ADHD deficits may not completely appear until adolescence or perhaps early adulthood due to the rates of brain growth and the increased demands for executive control as a person grows older.
The Mesocortical Pathway's Role In Schizophrenia
Schizophrenia is a mental illness that causes significant changes in perception, thought, emotion, and behavior. Symptoms begin to develop gradually in adolescence, and about half of those diagnosed are successfully managed to prevent episodic relapses. Positive, negative, and cognitive symptoms are used to classify symptoms.
Positive symptoms, or psychotic symptoms, are fleeting and nonspecific to schizophrenia, making early diagnosis challenging. Positive symptoms include persecutory delusions, hallucinations, and disorganized thoughts and speech. Individuals may also experience the passivity phenomena or distortions of self-experience, in which people with schizophrenia believe that their thoughts and feelings are not their own.
Negative symptoms include abnormal emotional responses and thought processes which can manifest as an absence of emotion, limited speech, an inability to experience pleasure, apathetic feelings, and a lack of desire to form relationships.
Apathy, one of the most common and significant negative symptoms, is related to abnormalities in the dopaminergic pathways involved in reward response and cognitive processing. Such pathways include the mesocortical pathway, which contributes to the cognitive function of the dorsolateral prefrontal cortex.
Neurobiological abnormalities in the mesocortical pathway may offer a probable explanation for the cognitive symptoms of schizophrenia. Cognitive symptoms are the earliest and most common symptoms in people with schizophrenia and are often present before the onset of the illness. Cognitive symptoms include deficits in neurocognition or social cognition.
Neurocognition is the ability to receive and remember information and includes verbal fluency, memory, reasoning, problem-solving, speed of processing, and auditory and visual perception. The mesocortical pathway's role in facilitating executive function may explain why individuals with neurobiological abnormalities associated with schizophrenia suffer from neurocognitive deficits.
Social cognition concerns the mental operations needed to interpret and understand the self and others in the social world. The mesocortical pathway facilitates the dorsolateral prefrontal cortex's secondary functions, including social cognition. Therefore, individuals with schizophrenia may have difficulty interpreting body language, facial expressions, and other social cues.
Several hypotheses attempt to explain the relationship between abnormal brain function and schizophrenia. The most widely accepted hypothesis proposes that schizophrenia is a neurodevelopmental condition associated with abnormal neurotransmitter transmission. The underlying neurobiological changes that arise before the appearance of symptoms occur in response to the interaction between genes and environmental factors such as maternal infections, malnutrition, and difficulties during pregnancy and delivery.
The most common of these theories is the dopamine hypothesis of schizophrenia which attributes psychosis to the mind's faulty interpretation of the misfiring of dopaminergic neurons. This theory has been supported by the success of medications targeting the dopamine receptor, increased dopamine levels during acute psychosis, and decreased dopamine receptors in the dorsolateral prefrontal cortex of individuals with schizophrenia.
The Mesocortical Pathway's Role in Parkinson's Disease
Parkinson's disease is a neurodegenerative illness in which dopamine-producing nerve cells in the brain are damaged and die. Tremor, stiffness, slow movement, and trouble walking are the most noticeable early signs. Many patients with Parkinson's disease experience despair, anxiety, and apathy, which can lead to cognitive and behavioral issues.
The deterioration of dopamine-producing nerve cells in the mesocortical pathway may explain some neuropsychiatric disturbances associated with the disease. In particular, the most common cognitive deficit associated with Parkinson's disease is executive dysfunction, which can be attributed to the low levels of dopamine transmission along the mesocortical pathway in the dorsolateral prefrontal cortex.
Cognitive problems can appear early in the disease, sometimes even before it is diagnosed, and they become more common as the disease progresses. Some of the most prevalent cognitive symptoms are problems with planning, cognitive flexibility, abstract thinking, rule acquisition, blocking incorrect activities, starting suitable actions, working memory, and attention management.
Likewise, difficulties in apathy and the ability to experience pleasure are common symptoms associated with the loss of dopaminergic neurons in the mesolimbic pathway. Therefore, individuals with Parkinson's disease frequently display reduced interest in activities that would previously have excited them, a lack of emotion, and indifference towards others.
Conclusion
The mesocortical pathway is a major dopaminergic pathway that connects the ventral tegmentum to the dorsolateral prefrontal cortex. This connection facilitates these brain regions' primary and secondary functions, including executive function, social cognition, and dopaminergic transmission.
The mesocortical pathway's involvement in dopamine transmission supports theories about the neurochemistry behind drug addiction and the hypotheses behind attention deficit disorder, schizophrenia, and Parkinson's disease.
References
https://en.wikipedia.org/wiki/Dorsolateral_prefrontal_cortex#Primary_functions
https://jamanetwork.com/journals/jamaneurology/fullarticle/794743
https://www.simplypsychology.org/brain-reward-system.html
https://en.wikipedia.org/wiki/Attention_deficit_hyperactivity_disorder#Pathophysiology
https://en.wikipedia.org/wiki/Schizophrenia#Cognitive_symptomshttps://en.wikipedia.org/wiki/Parkinson%27s_disease#Motor
