Neuro

Pathway
Curated for Inaura by: Inaura Writer Paul Kieffaber, PhD

The Brain

In 400 BCE, Hippocrates wrote, “Men ought to know that from nothing else but the brain come joys, delights, laughter and sports, and sorrows, griefs, despondency, and lamentations. And by this, in an especial manner, we acquire wisdom and knowledge, and see and hear, and know what are foul and what are fair, what are bad and what are good, what are sweet, and what unsavory […]. And by the same organ we become mad and delirious, and fears and terrors assail us […].” (Hippocrates, 1923).  Yet today, nearly 2,500 years later, we have yet to understand exactly how this marvelously complex organ (see Figure 1.) works.  

Today, scientists and practitioners with specialties in fields like Neuroscience, Psychology, Neurology, Cognitive Neuroscience, and Neuropsychology are simultaneously seeking answers to questions about the brain and developing new clinical techniques and interventions to improve the human condition. Appreciation of these clinical techniques and interventions can be facilitated by a general understanding of the brain’s anatomy, physiology, and chemistry.    

Neuroanatomy

In humans, the nervous system is made up of the brain, nerves, spinal cord, and sensory organs. The anatomy of the nervous system is typically described in terms of several subdivisions, including the central nervous system (CNS) and the peripheral nervous system (PNS).

Human Central Nervous System with Brain Anatomy
The Central Nervous System

The central nervous system consists of the brain and spinal cord. When asked to describe the brain, the first thing most people think about is its characteristically convoluted outer surface. This part of the brain is called the cerebrum or cerebral cortex and is believed to be the part of the brain responsible for much of the complex thinking and behavior that we consider unique to humans.

The cerebrum is divided down the middle into symmetric left and right hemispheres, each of which is further sub-divided into four lobes (see Figure 2).  The occipital lobe at the back of the brain is primarily responsible for your conscious vision.  The temporal lobes on either side of the head contain regions responsible for your ability to hear and understand language and contain regions critical for storing and retrieving memories.

The frontal lobes are, you guessed it, at the front of the brain and have been associated with a wide range of complex functions, including movement, decision-making, and emotion.  Finally, the parietal lobes are situated at the top of the brain in between the frontal, temporal, and occipital lobes.  The parietal lobes are sometimes called an “association” area of the brain because they communicate directly with all of the other lobes.  For example, one function of the parietal lobes is thought to be visual-spatial processing, which helps us to understand how to interact with our environment.

Beneath the folded outer surface of the cerebral cortex are a number of deep brain structures like the hypothalamus, the hippocampus, the amygdala, and the basal ganglia (see Figure 3). 

The hypothalamus is responsible for a number of motivated behaviors like hunger, thirst, and sexual behavior. The hippocampus has been linked with our ability to form new memories.  The amygdala is one of many areas in the brain that are associated with emotion.  Damage to or dysfunction of the amygdala can produce changes in how an individual experiences and/or expresses fear. Finally, the basal ganglia are a set of structures deep within the brain that are thought to be associated with the control of movement.  Movement disorders like those that occur with Parkinson’s disease are caused by dysfunction of the basal ganglia.

All of the cerebral cortex and its deep nuclei connect to the spinal cord via the midbrain and brainstem.  The midbrain contains some regions that function in vision and hearing, and others that are part of the voluntary motor system. The brainstem is made up of the pons and medula, structures that control many of the body’s vital functions such as heart rate, breathing, body temperature.  The brainstem is also directly connected to the cerebellum, a structure that is critical to balance and the coordination of movements.  Together, the structures of the brainstem and cerebellum are sometimes called the “reptilian brain” because these are the main structures found in a reptile’s brain and because they control simple behaviors that tend to be rigid and compulsive.

The Peripheral Nervous System

The peripheral nervous system (PNS) consists of all of the nerves entering and exiting the central nervous system (i.e., brain & spinal cord). The nerves of the PNS are what makes communication possible between the CNS and the other parts of your body (see Figure 4). The peripheral nervous system is further subdivided into the somatic nervous system and the autonomic nervous system. 

Figure 4. Showing Human Nervous System.
The Somatic Nervous System

The somatic nervous system consists of those nerves that carry the senses (e.g., touch, pain, temperature, etc.) from your extremities into the CNS and the nerves that carry the motor commands that help you move your muscles.

The Autonomic Nervous System

The autonomic nervous system consists of those nerves that communicate between the CNS and the visceral organs like the stomach, heart, and intestines.  Unlike the somatic branch of the nervous system, of which we are consciously aware, the autonomic branch of the peripheral nervous system controls unconscious activities like heart rate and digestion.  The autonomic nervous system can be further subdivided into its sympathetic and parasympathetic branches.

Activity in the sympathetic nerves generally leads to the mobilization of body energy. Constriction of some arteries, increase in heart rate, the inhibition of stomach contractions (i.e., digestion), and pupillary dilation are all consequences of sympathetic activation.  Sympathetic activation is commonly associated with the “fight or flight” response that occurs when body energy is mobilized to confront or flee a perceived threat.

Activity in parasympathetic nerves generally leads to the conservation and storing of body energy.  Dilation of some arteries, inhibition of the heart rate, increased stomach contractions, and pupillary constriction are all consequences of parasympathetic activation.  Because the consequences of parasympathetic activation are antagonistic to fight or flight response from the sympathetic nervous system, parasympathetic activation is often associated with the expression “rest and digest.”

It is important to remember that all of the above-mentioned divisions and branches of the nervous system are connected to one another through a sprawling network of nerves.  Consideration of the connectivity between these systems of the brain has led to a number of theories about how they interact.  One example of that interaction is illustrated in polyvagal theory.

 

Polyvagal Theory

 

Image of vagus nerve (yellow) and all of the organs it impacts.

Polyvagal theory describes a theory put forward by some psychologists and neuroscientists implicating activation of the vagus nerve in a person’s ability to regulate their emotions (including the fear response) and feelings of social connection.  The vagus nerve is a critical component of the parasympathetic nervous system.  It is one of 12 cranial nerves, and it enters/exits the brainstem and innervates the heart, lungs, and stomach.

Advocates of polyvagal theory are focused on evolutionary changes in the neural circuits of the “reptilian brain” (the brainstem and cerebellum) in humans.  Changes in how the vagus nerve interacts with the heart are believed to be the foundation of a face–heart connection that creates a sort of social engagement system linking social interactions to the regulation of autonomic nervous system functions. In essence, polyvagal theory attempts to explain why social interactions are so closely connected to our physiological and emotional states (Porges, 2009).

 

According to Polyvagal theory, there are three primary states of being:

    • Parasympathetic/Ventral Vagal – System of safety, connection, health, growth, restoration
    • Sympathetic Activation – System of mobilization | Protection through action: fight, flight, etc.
    • Parasympathetic/Dorsal Vagal – System of immobilization | Protection through disappearing & freeze

Neurophysiology

Neurophysiology is a branch of neuroscience that focuses on questions about how the brain functions.  Since, like the rest of our bodies, the brain is made up of cells, understanding the physiology of the brain means understanding how the cells of the brain (mainly neurons and glial cells) receive and transmit information. 

The Neuron

In many ways, neurons are like any other cell in the human body.  For example, they contain ribosomes for synthesizing proteins and a nucleus that contains genetic material (i.e., DNA and RNA), and they are surrounded by a specialized cell membrane that holds everything together and prevents some things from moving in and/or out of the cell.  One of the most obvious things that makes brain cells different is their shape.  Whereas most cells of the body have a round or oblong shape, brain cells have a number of special appendages that allow them to both receive signals (i.e., “information”) from some neurons and send signals to other neurons. An example of a prototypical neuron is depicted in Figure 6 below.

Figure 6. Typical Nerve Call

 

The parts of the neuron that receive signals from other neurons are branching structures called dendrites.  Depending on the nature of the signals received by the dendrites, the neuron may or may not “decide” to send that signal to other neurons in the brain. When conveying that signal onward, it travels from the cell body, down a long appendage called the axon, to the axon terminals. Neurons can greatly range in size. Some neurons are microscopic, whereas others have axons that are so long that they begin at the spinal cord and end at the tip of your toes! Once the signal reaches the axon terminals, it is conveyed to the signal-receiving dendrites (see Figure 6) of other neurons, which may or may not forward the signal again depending on other signals received by other neurons. This concept of neural signaling is important for understanding how neurons communicate with each other.

How Neurons Communicate

Even as you read this article, the various parts of your computer are communicating with one another.  For example, your computer monitor (or tablet screen) is communicating with the video module by sending electrical impulses that tell your monitor which pixels should light up and when. Suppose you unplug your monitor from the computer. In that case, both the computer and the monitor are still perfectly capable of sending and receiving signals, but the screen will be blank because the two components aren’t connected.  Communication between neurons can be understood similarly.

The movement of signals from one end of the neuron to the other end is similar to the movement of electrical charges in the wiring of your computer or even the wiring of your home, except that the electrical signals that powered up your coffee maker this morning rely on the movement of electrons and the signals that move from one end of the neuron to the other rely on the movement of charged particles like sodium and potassium. When one neuron receives signals from another neuron and decides to send that signal forward, it does so by sending a wave of these charged particles in what is typically referred to as an electrical or neural impulse.

However, just the way your monitor won’t light up unless it is plugged into the computer, neurons need to be “plugged into” other neurons for the brain to work.  On your computer, the connections between components are often plugs that create direct connections between components through which electrons can flow. However, this is where the similarities between computers and the brain end.  Communication between neurons in the brain occurs at millions of tiny connections called synapses (see Figures Below).  Rather than direct connections between neurons, the synapse includes a small space through which the signal must pass.  Here, the axon terminal releases chemicals called neurotransmitters that must cross the space in the synapse and attach to specialized receptors on the dendrites of the receiving neuron.  This is the way that signals pass from one neuron to the next. When that happens, the receiving neuron may or may not send a nerve impulse down its own axon and release more neurotransmitters to be received by yet another neuron.  

Nerve to nerve communication
Synapse & Neurotransmitters passing

 

 

 

 

 

 

 

 

 

 

Importantly, it is the billions of chemical transactions between neurons (the sending and receiving of neurotransmitters) that keep our brains functioning normally.  Healthy neurotransmission helps regulate everything from our heart rate to digestion of the food we eat to our ability to concentrate on our emotional states and psychological well-being.

Neurotransmitters

The neurotransmitters released at the synapse can have various effects on the neurons whose dendrites they bind with.  In general, there are two things that determine the kinds of effects they have: (1) the type of neurotransmitter, and (2) the type of receptor to which they bind.  For present purposes, we will focus on the various types of neurotransmitters and an overview of their primary functions.   

Glutamate

Glutamate is the major excitatory neurotransmitter in the brain.  This means that, when released by a neuron, glutamate tends to excite the receiving neuron and cause that neuron also to release its neurotransmitter (which could be more glutamate or something else). Our diet can be a major source of the chemicals used to create glutamate as it is an amino acid that can be found in meat and food additives like monosodium glutamate (MSG) found in things like soy sauce. 

Both an overabundance or deficiency of glutamate can affect your psychological functioning.  For example, increased levels of glutamate have been associated with increased pain and pain sensitivity in healthy adults, and abnormalities in glutamate levels have been associated with various psychiatric conditions like obsessive-compulsive disorder (OCD), anxiety, posttraumatic stress disorder (PTSD), and schizophrenia (Kraal et al., 2020).

Gamma-aminobutyric Acid (GABA)

GABA is the major inhibitory neurotransmitter in the brain. This means that, when released by a neuron, GABA tends to inhibit (i.e., suppress) the activity of the receiving neuron, causing that neuron to be less likely to itself further release neurotransmitters. GABA is synthesized in our bodies from glutamate.  If you have ever had more than one or two alcoholic beverages in a short period of time, then you have probably experienced the effects of increased GABA activity as drugs like alcohol and benzodiazepines (e.g., Xanax) increase activity at the GABA receptor. Like glutamate, GABA has been linked with many cognitive and psychological functions and recently has been suggested to be a promising therapeutic target for anxiety and depression (Blum & Mann, 2002; Felice et al., 2020; Prévot & Sibille, 2021)

Acetylcholine

In the brain, acetylcholine affects neurons in a variety of ways, but this neurotransmitter also participates in a number of important functions of the nervous system outside the brain, too.  Learning and memory are just two of the cognitive functions that have been linked with acetylcholine (and the neurons that secrete it).  In the peripheral nervous system, acetylcholine plays a significant role in our ability to move our skeletal muscles.  The motor neurons that leave the spinal cord and connect with the muscle fibers of our bodies release acetylcholine where it acts as an excitatory neurotransmitter, stimulating contractions of the muscles. In other parts of our bodies, acetylcholine can act as either an inhibitory or an excitatory neurotransmitter, depending on where it is released.  For example, the release of acetylcholine at the heart muscle can either slow or increase the heart rate depending on which part of the nervous system (sympathetic or parasympathetic) does the releasing. 

Serotonin 

Serotonin is a special kind of neurotransmitter known as a neuromodulator with complex effects on multiple brain and bodily functions.  In the brain, serotonin can be found in high concentrations in various nuclei of the brainstem.  Serotonin is perhaps best known for its role in a wide range of neuropsychological functions, including depression, and drugs that target serotonin (e.g., SSRIs like ProzacTM) receptors are widely used in the fields of psychiatry and neurology. It is interesting to note, however, that most serotonin is found outside of the central nervous system. In the body, serotonin is known to regulate processes like cardiovascular function, bowel motility, ejaculatory latency, and bladder control (Berger et al., 2009).    

Dopamine

Dopamine is a neurotransmitter that is known to play a vital role in both movement regulation and reward processing. Increased dopamine transmission occurs in the brain in response to any type of reward and occurs with the use of most addictive drugs. In fact, both dopamine and serotonin are sometimes referred to as the “happy hormones” due to their role in emotion regulation. Conversely, dysfunction of the dopamine system has been implicated in different nervous system diseases, including Parkinson’s disease, schizophrenia, and addiction.

Brain Rhythms

The term “brain rhythms” is sometimes used to describe rhythmic, repetitive oscillations in the electrical activity of neurons.  Recall that the movement of signals from one end of the neuron to the other end is similar, in principle, to the movement of electrical charges in the wiring of your home electronics, except that the signals moving around inside neurons rely on the movement of charged particles like sodium and potassium. Whenever these charged particles move around, there are changes in the electrical fields they produce. These electrical fields move through the brain, skull, and scalp and can be recorded using technologies like the electroencephalogram (EEG).  Of course, the electrical field produced by the activity of a single neuron would be far too small to be detectable at the scalp, but when thousands or millions of neurons are active at the same time, the electrical fields sum together and can be recorded using EEG.

Neural oscillations are most often described in terms of their amplitude (i.e., magnitude) and frequency, measured in units hertz (Hz), which translates to the number of cycles per second.  For example, a neuron that is less active might receive/transmit neurotransmitters three times per second, or at a frequency of 3 Hz. Another neuron that is more active might receive/transmit neurotransmitters at a frequency of 15 times/second or 15 Hz. These different rates of neural activity would produce different oscillations of the electrical fields recorded with EEG.  The amplitude of an oscillation simply refers to its magnitude.  For example, the 3Hz oscillation in has a larger amplitude than the 12Hz oscillation.

Female Patient in a Neurology Lab doing EEG Scan

The neural oscillatory activity recorded by EEG is a combination of the neural oscillations from many millions of neurons and so it is commonly measured in grouped frequency bands as opposed to specific frequencies like 3Hz and/or 12Hz.  These frequency bands typically range from 1Hz to 70Hz and are grouped into Delta (1-2Hz), Theta (3-7Hz), Alpha (8-12Hz), Beta (13-29Hz), and Gamma (30-70Hz) bands.  Importantly, neural oscillations in each of these bands are thought to be related to a number of cognitive and psychological functions.  Figure 9 depicts realistic recordings of neural oscillations in each of the above-mentioned frequency bands. 

Realistic Record of neural oscillations in each of the frequency bands above.
Delta Oscillations (1-2Hz)

Delta waves are the slowest brain waves and are most closely associated with stages 3 and 4 of sleep (deep sleep). However, increased levels of concentration and even meditation have also been associated with increased delta wave activity, particularly that recorded over the frontal cortex. 

Theta Oscillations (3-7Hz)

Theta oscillations are also considered “slow” brainwaves.  Their role in memory has been well-documented by neuroscientists, with increased theta being associated with the conversion of new experiences into long-term memory.  Theta is also increased during meditation and daydreaming and is associated with creativity and insight.

Alpha Oscillations (8-12Hz)

Generally speaking, alpha is the prominent EEG rhythm in awake adults who are still conscious but relaxed with their eyes closed. Alpha rhythms can be recorded at all locations around the head, but the occipital and parietal regions of the cerebral cortex tend to produce the strongest alpha oscillations. Alpha is often reduced (“blocked”) by cognitive processing.  For example, alpha waves in the visual cortex are drastically reduced when one opens their eyes.  Although still debated by some scientists, there is evidence that alpha asymmetry between the two hemispheres of the brain (e.g., more alpha in the right than the left) may be related to some psychological disorders like depression. 

Abnormal alpha rhythms have also been repeatedly described in attention deficit hyperactivity disorder (ADHD).  In ADHD, reduced alpha rhythms are associated with reduced inhibition, and some research has demonstrated that neurofeedback techniques directed at increasing alpha can normalize the alpha rhythm in adults with ADHD (Deiber et al., 2020).

Beta (13-29Hz) & Gamma Oscillations (30-70Hz)

Beta and Gamma rhythms are considered the “fast” brain oscillations and occur in individuals who are alert, attentive, and/or exerting mental effort.  Interestingly, these faster EEG rhythms are also present during REM (Rapid Eye Movement) sleep. Thus, these faster EEG waves are believed to reflect peak arousal of the cerebral cortex during complex cognitive processes.

Although the lion’s share of clinical research related to the various brain rhythms has focused on alpha and theta oscillations, research suggests that delta and beta/gamma rhythms may also have roles to play. A recent meta-analysis (a study of past literature) suggests that there are consistent differences in each of these primary frequency bands in conditions like depression, ADHD, schizophrenia, addiction, autism, OCD, bipolar, and PTSD (Newson & Thiagarajan, 2019). In fact, it is this exciting new research that has driven the development of new intervention techniques like neurofeedback.

Neurofeedback

Have you ever been connected to an electrocardiogram (EKG) that made a beeping sound with every heartbeat?  If you have, then you may have experimented with trying to make the beeping sound slow down or speed up just by concentrating on the speed of the beeping.  This example of trying to control the sounds from the EKG is a form of biofeedback in which heart rate is the biological function measured and the feedback is the beeping sound.  

Neurofeedback is a kind of biofeedback. Just like biofeedback can be used to teach one self-control of their heart rate, the goal of neurofeedback is to teach one self-control of brain functions. There are several types of neurofeedback (see Marzbani et al., 2016 for a review), but the most common is frequency/power neurofeedback which measures neural oscillations with EEG and provides a feedback signal that can be either an auditory tone and/or visual feedback on a computer screen. Provided with positive and/or negative feedback about desirable and/or undesirable brain activities, neurofeedback can be used to train you (i.e., your brain) to produce a pattern of neural oscillations that is associated with improved mental health and general health outcomes.

Neurofeedback really isn’t a new concept.  In fact, people have been using neurofeedback for decades.  What is new is that modern technological developments and the advancement of desktop computing have made neurofeedback far more accessible than it once was. 

Close up portrait of a smiling woman touching the silicone EEG cap on her head

The increasing commercial availability of EEG recording systems even makes it possible for people to record their brain rhythms at home, opening new opportunities for the application of neurofeedback techniques in telehealth environments.

 

Neurofeedback treatment protocols tend to focus on the categories of brain waves just described, namely alpha, beta, delta, theta, and gamma oscillations or some combination of these.  

 

References:

Berger, M., Gray, J. A., & Roth, B. L. (2009). The Expanded Biology of Serotonin. Annual Review of Medicine, 60(1), 355–366. https://doi.org/10.1146/annurev.med.60.042307.110802

Blum, B. P., & Mann, J. J. (2002). The GABAergic system in schizophrenia. International Journal of Neuropsychopharmacology, 5(2), 159–179.

Deiber, M.-P., Hasler, R., Colin, J., Dayer, A., Aubry, J.-M., Baggio, S., Perroud, N., & Ros, T. (2020). Linking alpha oscillations, attention and inhibitory control in adult ADHD with EEG neurofeedback. NeuroImage: Clinical, 25, 102145. https://doi.org/10.1016/j.nicl.2019.102145

Felice, D., Cryan, J. F., & O’Leary, O. F. (2020). GABAB Receptors: Anxiety and Mood Disorders (pp. 1–25). Springer. https://doi.org/10.1007/7854_2020_171

Hippocrates. (1923). Hippocrates. Harvard University Press.

Kraal, A. Z., Arvanitis, N. R., Jaeger, A. P., & Ellingrod, V. L. (2020). Could Dietary Glutamate Play a Role in Psychiatric Distress? Neuropsychobiology, 79(1–2), 13–19. https://doi.org/10.1159/000496294

Marzbani, H., Marateb, H. R., & Mansourian, M. (2016). Neurofeedback: A Comprehensive Review on System Design, Methodology and Clinical Applications. Basic and Clinical Neuroscience, 7(2), 143–158. https://doi.org/10.15412/J.BCN.03070208

Newson, J. J., & Thiagarajan, T. C. (2019). EEG Frequency Bands in Psychiatric Disorders: A Review of Resting State Studies. Frontiers in Human Neuroscience, 12. https://doi.org/10.3389/fnhum.2018.00521

Porges, S. W. (2009). The polyvagal theory: New insights into adaptive reactions of the autonomic nervous system. Cleveland Clinic Journal of Medicine, 76(Suppl 2), S86–S90. https://doi.org/10.3949/ccjm.76.s2.17

Prévot, T., & Sibille, E. (2021). Altered GABA-mediated information processing and cognitive dysfunctions in depression and other brain disorders. Molecular Psychiatry, 26(1), 151–167. https://doi.org/10.1038/s41380-020-0727-3

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