HOW THE BRAIN PROCESSES THOUGHTS AND EMOTIONS, AND HOW TO MODULATE NEGATIVE EMOTIONS
The processing system for positive and negative emotions
JILL KARATINOS, M.S., M.D.
I. INTRODUCTION:
The importance of this info has to do with what these treatments target in the brain, rather than just picking a drug that a pharmaceutical company is selling for a specific treatment. Sociopathy in particular is not well understood by those outside of the field. Neurotransmitters, neurocircuitry, and neuroreceptors are topics not well known to other clinicians, but are very cogent for anyone prescribing drugs.
Psychiatry is now a brain science, not pill peddling, or talk therapy. That needs to be recognized by other clinicians, who have sometimes discounted us as not really practicing medicine. My subspecialty of neuropsychiatry is particularly proud of its contributions to modern medicine, chronicled in the American Psychiatric Association Journal, and in The Journal of Neuropsychiatry and Clinical Neurosciences, the most recent edition of which I received today, with a lead article somewhat similar to the one I wrote, on the way the habenula processes negative and positive emotions. The brain is unknown territory for most physicians, and it would be interesting to see any commentary.
The brain has centers and circuits to process the positive emotions of joy, serenity, and motivation, but also the negative emotions such as fear, anger, hate, irritability, disgust, and sociopathy(aggression associated with spectrum of antisocial personality disorder).
Research in these areas promises better control over our emotions.
If these areas were examined by certain neuroimaging procedures (fMRI and PET scans), it would be discovered that, although the circuits of the positive emotions look the same in most people, the negative emotions are more variable, with deficiencies and over-activities in some of the circuits compared to persons with less negativity.
The circuitry in question consists of emotion/cognition anatomic circuits in the brain. The top level is that of the cortex of the frontal lobe, with the second level being a system called the limbic system, which consists of the cingulate gyrus, hippocampus, amygdala, and insula in the temporal lobe, and the hypothalamus.
Below the flow from the cortex through the limbic system-hypothalamus would be the basal ganglia and thalamus, and below that level would be the brainstem. There is a flow back and forth among these systems in a circular manner (See Figure 1 and Figure 2 — the processing system for positive and negative emotions, Figure 1, sagittal view of brain and the direction of flow in the system, Figure 2, next 2 pages). Figure 1 is a medial view, so the dorsolateral prefrontal cortex (DLPFC) is not seen because it is external. This is also the reason why the basal ganglia is not seen in this cut.
II. EMOTION-COGNITION CIRCUITS
A. Portions of the frontal lobe called the prefrontal cortex (PFC), dorsolateral prefrontal cortex (DLPFC), and orbitofrontal cortex (OFC) , as seen in Figure 1, are connected to the evolutionarily older portion of the brain called the limbic system, which underlies emotional combined with cognitive processing in the hippocampus. To clarify, the PFC or DLPFC is our locus for voluntary control over our emotions, with the OFC the center for inhibiting impulsivity. Disinhibition and lack of ability to control impulses resides in an abnormal portion of the orbitofrontal cortex (OFC), while apathy is related to a deficiency in the DLPFC- reward center circuit.
A recent review paper on “ A Systematic Review of the Neural Correlates of Positive Emotions”, eg, happiness, searched 12 studies from 1995 to 2016 of neuroimaging and EEGs (Machado and Cantilino 2017) and found mixed, often inconsistent, results. A few generalizations stand out. It stated only 35 to 50% of the variance was due to genetics and personality traits. Happiness activated reductions in activity in the right PFC and temporoparietal cortices bilaterally, and increased activity in the in dorsolateral(DLPFC) and medial PFC, the cingulate cortex, the inferior and medial temporal gyri, the amygdala, and ventral striatum. Left PFC damage or hypoactivity is associated with depression. Right sided damage, particularly temporal lobe, is correlated with mania.
Extraverts showed more resilience, being less sensiitve to negative, but more sensitive to positive, stimuli.
B. The core of the limbic system is the anterior cingulate cortex (ACC), connected to the reward system, which is comprised of the nucleus accumbens (NA) attached to the basal ganglia/striatum. Pleasure and happiness occur here. That is, when a person enjoys good food, is moved by art or literature, feels love, or personal accomplishment, the neurotransmitter, dopamine, stimulates the nucleus accumbens, and pleasure or serenity or joy is the result. Difference in quality of emotion, eg, enjoyment of food versus love for a child, must certainly be distinct, but I did not encounter in any papers what the distinction is in terms of neural transmission.
C. However, the reward system can be co-opted by the counterfeit pleasures of addiction, whether to alcohol, drugs, gambling, pornography, or sexual addiction. These pleasures may supersede life’s simpler pleasure in the reward system by increasing the amount of dopamine needed to feel pleasure. Methamphetamine, for example, can actually bankrupt the system of dopamine in the nucleus accumbens, thus requiring restoration of the dopamine neurotransmitter.
Cognitive decision making areas of the prefrontal cortex such as the dorsolateral prefrontal cortex (DLPFC) can override the lower center of the nucleus accumbens. The more a circuit is activated, the more it becomes prevalent. For example, every time your reasoning DLPFC over comes your reward center’s craving for alcohol, that choice is strengthened, and every time a drug relapse occurs, that choice is strengthened.
D. The amygdala part of the limbic system promotes aversive responses to stimuli, which can also be overridden by the PFC. The amygdala is the major center for fear and rage, but has also been noted to give a positive or negative emotional valence to experiences that are occurring.
E. Adjacent to the amygdala is the hippocampus, which is found in the temporal lobe along with the amygdala. The hippocampus/amygdala circuit is also where fear, anger, and aggression are processed, along with memory. The amygdala carries episodic/autobiographical memory. This hippocampal/amygdala circuit underlies the development of posttraumatic stress disorder (PTSD) and panic disorder.
F. The psychopharmacologist/psychiatrist Dr. Stephen Stahl has a diagram matching symp- toms to malfunctioning brain circuits in schizophrenia, page 84, Stahl’s Essential Psychopharmacology 4th edition (2013). Affective symptoms such as depression, are associated with ventrolateral prefrontal cortex (VMPFC) , aggressive symptoms with OFC and amygdala, cognitive symptoms such as poor decision making with DLPFC , negative symptoms associated with mesocortical prefrontal cortex, and NA/reward circuit , and the symptoms of hallucinations and delusions associated with mesolimbic areas. In this case, the prefix meso refers to midbrain. Similar diagrams are shown on pages 357 and 358, in the chapter on parts of the brain associated with each symptom of depression, and the neurotransmitters associated with each symptom, eg, anxiety with low 5HT (serotonin) and GABA, sexual dysfunction with dopamine(DA), insomnia or hypersomnia with DA, NE and histamine.
III. SOCIOPATHY
Sociopathy is a part of the spectrum of antisocial personality disorder, in which are found traits of lack of empathy, extreme self-interest, cheating, lying, dominating, stealing, and even murder, some or all of which have been seen in this disorder. Sociopathy may be genetically inherited, or may be acquired from a brain injury.
People with sociopathy do not have the emotional component of” theory of mind”, meaning being able to imagine and understand the feelings/behavior of others, paired with empathy, which means that you actually feel the feelings of another person. Sociopathy has been shown to be associated with an alteration of neurotransmitters in the DLPFC, ACC, and orbitofrontal cortex (OFC) functions, without normal serotonergic modulation. Put another way, the reasoning apparatus of the prefrontal cortex is deficient in signaling the limbic system (empathy) and in the lower brain centers with regard to behavior. In addition, the circuitry to the reward center in the nucleus accumbens is defective. Thirdly, a recent research paper details that serotonin, a neurotransmitter associated with serenity and positivity, which ordinarily modulates the PFC- limbic circuitry, does not operate properly in sociopaths.
IV. NEUROTRANSMITTERS
Neurotransmitters associated with emotions that stimulate the circuits are dopamine (DA) and noradrenalin (also called norepinephrine=NE) , acetylcholine (ACH), and glutamate. Medications which stimulate the NE, DA, or ACH receptors are called NE, DA, or ACH agonists. However, too much of any of the neurotransmitter agonists can paradoxically result in overactive responses, such as mania or ADD in the prefrontal cortex (PFC). NE acting in the amygdala generates fear, anger, panic, aggression. Either the PFC or the hippocampus may over-ride these feelings.
A further qualifying generalization is that there are other neurotransmitters that modulate dopamine, norepinephrine and acetylcholine, such as serotonin or gamma amino butyric acid, called GABA, which have a calming effect. A second qualifier applies to which brain circuit the neurotransmitter is acting, as to how behavior is influenced.
Neurohormones, such as cortisol, aldosterone, or estrogen/testosterone are released from the hypothalamus/pituitary axis to affect the circuits under discussion.
V. CLINICAL APPLICATIONS
In the treatment of post-traumatic stress disorder (PTSD), which encompasses many negative emotions, such as panic, fear, and rage, serotonergic agents such as sertraline, duloxetine, or escitalopram have been primary. Some anticonvulsant agents, such as topiramate, have been useful. The use of benzodiazepines, such as diazepam, lorazepam, alprazolam, clonazepam are contraindicated, not only because they are addictive, but because they become ineffective and disinhibiting. They also suppress reflexes, slow wave sleep, and memory.
Serotonergic agents are also the drugs of choice for panic disorder, with contraindications for benzodiazepines.
In the treatment of apathy from brain injury or stroke, NE or DA agonists such as methylphenidate, bupropion, or amantadine are effective. They target the OFC. These are also used in attention deficit disorder ADD, targeting the DFPLC.
In the treatment of drug addiction in the reward circuit, an agent must be given to counteract the hyperactivity of the sensorimotor and autonomic systems due to drug withdrawal. Clonidine, which decreases norepinephrine (NE) output to the brainstem or baclofen, a GABA B agonist, or carbamazepine, an anticonvulsant, may serve in this capacity. I have found the continued use of gabapentin, a ligand binding to calcium channel blockers to block release of excitatory neurotransmitters (eg, glutamate) often indefinitely, may prevent craving and relapse after withdrawal is accomplished. Treatment of accompanying psychiatric disorders and attendance at substance abuse groups is important in preventing relapse. This is strengthening the DLPFC to inhibit the choosing to relapse.
Sexual addiction is best treated with serotonergic agents, and in men, progesterone, increased progressively, to lower testosterone levels. Hypersexuality may be a symptom in mania, which would require treatment of bipolar disorder, or of dissociative disorder in those with a history of sexual abuse.
Psychotherapy should be part of any treatment plan, including cognitive, motivational, supportive, interpersonal, and exposure therapy. This is targeting the DFPLC.
Transcranial magnetic stimulation (TMS) has been tried, to modulate impaired empathy. 18 studies of this were identified. (Yang, et al. Psychol Med 2017 Aug 22:1–4.) A small effect was shown on “healthy individuals”, but it is not clear if these had sociopathy.
Electronically Signed By:
Gillian (Jill) Karatinos, M.D.
Diplomate American Board of Psychiatry and Neurology
Diplomate, UCNS Neuropsychiatry
For bio and more info see www.jillkaratinosmd.com
