The electroencephalograph (EEG) monitors slow cortical potentials and fast potentials that exceed 50 Hz. The EEG records the EPSPs and IPSPs in the dendrites of pyramidal cells in the upper cortical layers. Neurons work in partnership with glial cells, which themselves are a source of slow cortical potentials. There are multiple generators of the EEG rhythms that are studied and shaped by neurotherapists. Intracellular and extracellular studies provide evidence of a corticothalamic network that is responsible for multiple EEG rhythms. These waveforms appear to be grouped by slow cortical potentials.

This unit discusses Specific central nervous system structures and neurotransmitter pathways and neurotransmitter pathways (VI-A), Neuronal sources of scalp EEG activity (VI-B), and EEG patterns and their behavioral correlates (VI-C).

Students completing this unit will be able to discuss:

  1. Neuron and glial cell structure and function
  2. Communication between neurons
  3. The source of the EEG
  4. EEG frequencies
  5. General cortical anatomy
  6. General subcortical anatomy

While no one has actually counted the neurons in the human nervous system, there may be over 200 billion neurons in the adult human brain. There are 10 times more glial cells than neurons and they comprise 50% of the brain’s volume (Travis, 1994). The 2 trillion glial cells are considerably smaller than neurons, with somas between 6 to 10 μm in diameter (Hammond, 1996).

Several thousand synaptic connections are made on an average neuron in the human brain. If we accept the estimate that the brain contains 1011 neurons, then the total number of synapses exceeds 1014, or trillions. This estimate excludes neural communication with astrocytes, star-shaped glial cells, which communicate with and support neurons, and help determine whether synapses will form.

Imagine the tip of an unsharpened pencil, which is 2 mm across. Neurons are 40-200 times smaller. Their small size prevented the study of neurons until developments in microscopy and histology (Bear, Connors, & Paradiso, 2007).

Sensory neurons are specialized for sensory intake. They are called afferent because they transmit sensory information towards the central nervous system (brain and spinal cord).

Motor neurons convey commands to glands, muscles, and other neurons. They are called efferent because they convey these instructions away from the central nervous system (Carlson, 2007).

provide the integration required for decisions, learning and memory, perception, planning, and movement. They have short processes and are confined to the central nervous system.

Neurons contain a soma, dendrites, and axon. The cell body or soma contains machinery for cell life processes and receives and integrates EPSPs and IPSPs from axons, which are generated by axosomatic synapses (junctions between axons and somas). The cell body of a typical neuron is 20 μm in diameter, and its spherical nucleus, which contains chromosomes comprised of DNA, is 5-10 μm across.

Dendrites are branched structures designed to receive messages from other neurons via axodendritic synapses (junctions between axons and dendrites).

Dendritic spines are protrusions on the dendrite shaft where axons typically form axodendritic synapses.


Dendrites also send messages to other neurons via dendrodendritic synapses (junctions between dendrites).

During learning, the number and size of spines may increase to enlarge the potential contact area. In special cases, dendrites integrate EPSPs and IPSPs and produce action potentials called spikes (Wilson, 2003).

Stewart challenged neuroscientific dogma when he discovered in 1979 that dendrites can contain synapse-associated polyribosome complexes (SPRCs), which can produce proteins that allow rapid remodeling of synapses. A polyribosome complex consists of several ribosomes bound to messenger RNA (mRNA). SPRCs represent one mechanism underlying synaptic plasticity (Bear, Connors, & Paradiso, 2007).

Axons are long, cylindrical structures that convey information from the soma to the terminal buttons. Axons also transport molecules in both directions along the outer surface of protein bundles called microtubules. This process is called axoplasmic transport. Axons range from 0.002 mm to 0.02 mm in diameter, and 0.1 mm to 3 meters in length (Garrett, 2003). Over 90% of neurons are interneurons whose axons and dendrites are very short and do not extend beyond their cell cluster.

The axon hillock is a swelling in the cell body where a neuron integrates the messages it has received from other neurons and decides whether to fire an action potential (Carlson, 2007).

Terminal buttons
are buds located on the ends of axon branches that form synapses and release neurochemicals to other neurons. Terminal buttons contain vesicles that store neurotransmitters for release when an action potential arrives. A terminal button’s presynaptic membrane may contain reuptake transporters that return neurotransmitters from the synapse or extracellular space for repackaging.


Axons can influence the amount of neurotransmitter that is released when an action potential arrives at a terminal button through axoaxonic synapses (junctions between two axons). Axoaxonic synapses do not affect the generation of an action potential, only the amount of neurotransmitter that is distributed. In presynaptic facilitation, a neuron increases the presynaptic neuron's neurotransmitter release by delivering a neurotransmitter that increases calcium ion entry into its terminal button. In presynaptic inhibition, a neuron decreases neurotransmitter release by reducing calcium ion entry. These modulatory effects are confined to a single synapse.

A neuron's axon has an electrical charge called a membrane potential. The term potential means stored electrical energy, analogous to the energy contained in a battery.

When a neuron is not influenced by messages from other neurons, this potential is called a resting potential. A typical resting potential is about -70 millivolts (thousandths of a volt), since the inside of a resting axon is more negatively charged than the outside.

A -70 mV membrane potential represents a balance between the forces of diffusion and electrostatic pressure.

Diffusion is the distribution of molecules from areas of high concentration to low concentration. Pour sugar into a glass of water. After the sugar molecules settle to the bottom, they will evenly spread throughout the glass without stirring the liquid.

In the case of neurons, diffusion involves the movement of charged particles called ions between the extracellular fluid surrounding the axon and the intracellular fluid contained within the neuron.

Electrostatic pressure is the attractive or repulsive force between ions that moves them from one region to another. Ions are charged particles with a positive or negative charge. Positive ions are called cations and negative ions are called anions.

Ions with different charges attract each other (cations attract anions). Ions with the same charge repel each other (two cations or two anions repel each other). Electrostatic pressure draws cations toward areas where anions are highly concentrated and pushes them away from other cations (Carlson, 2007).

Neurons communicate through the release of neurochemicals and ions. Axon terminal buttons release neurochemicals across a fluid-filled gap called a synaptic cleft and into the extracellular fluid surrounding the neuron.

The major groups of neurochemicals are shown below. The amino acids and biogenic amines (ACh, histamine, monoamines) are especially critical to the production of the EEG. These neurochemicals travel to binding sites on receptors located on or inside other neurons. When they attach to a binding site, like a key in a lock, they can produce rapid or slow changes in the target neuron's membrane potential.


The amino acid neurotransmitters belong to the oldest family of transmitters. These molecules mediate information-transmitting effects. In the brain, most synaptic communication is accomplished by glutamate (excitatory) and GABA (inhibitory). The other neurotransmitters generally have modulating effects, meaning that they alter other neurons’ performance.


Glutamate is the primary excitatory neurotransmitter in the brain, and its receptors are found of the surface of almost all neurons. There are at least 13 different receptors for glutamate, 5 ionotropic and 8 metabotropic. Most presynaptic neurons in the brain excite postsynaptic neurons via ionotropic glutamate receptors in the postsynaptic membrane. These ionotropic receptors fall into two classes: NMDA receptors and non-NMDA receptors (AMPA and kainate). Metabotropic glutamate receptors may play a regulatory function, either augmenting or suppressing the activation of ionotropic glutamate receptors.

Caption: In the normal brain the prominent glutamatergic pathways are the cortico-cortical pathways; the pathways between the thalamus and the cortex; and the extrapyramidal pathway (the projections between the cortex and striatum). Other glutamate projections exist between the cortex, substantia nigra, subthalamic nucleus, and pallidum. Glutamate-containing neuronal terminals are ubiquitous in the central nervous system and their importance in mental activity and neurotransmission is considerable.

Long-term potentiation (LTP) is an increase in the excitability of a postsynaptic neuron after repeated high-frequency stimulation by a presynaptic neuron. LTP allows neurons to remodel their synapses in response to learned associations. This form of neuronal plasticity appears to be the basis of explicit learning, behavioral changes that occur with our conscious awareness.

A synapse is strengthened when it is active and the postsynaptic neuron is depolarized. Glutamate binds to AMPA (glutamate) receptors on the dendritic spine of a postsynaptic neuron, which opens sodium channels, depolarizes the neuron's membrane (producing an EPSP), and dislodges a Mg+ ion that blocks an adjacent NMDA (glutamate) receptor's calcium channel. Now, when glutamate and D-serine or glycine bind to the glycine site on the NMDA receptor, calcium enters the spine, resulting in a large, prolonged increase in intracellular calcium (Snyder et al., 1999). Astrocytes may influence LTP through control of extracellular concentrations of D-serine or glycine (Yang et al., 2003).

Caption: The NMDA receptor is one of the main mediators of excitatory neurotransmission. The binding of both glutamate and glycine activates this receptor. The receptor is a ligand-gated ion channel, which permits the movement of calcium, sodium, and potassium across the postsynaptic membrane.

Calcium entry into the dendritic spine moves AMPA receptors into the postsynaptic membrane. LTP causes structural changes in the synapse, like "perforated synapses," where the axon terminal button forms two synapses with the same dendritic spine. LTP involves the synthesis of a gaseous retrograde transmitter, nitric oxide, in the dendritic spine, which travels to nearby terminal buttons to increase glutamate release. Researchers believe that LTP has early and late stages, and that long-lasting LTP requires the synthesis of proteins in the cell body and their transport to "tagged" activated dendritic spines (Carlson, 2007).

Long-term depression (LTD) is a reduction in the excitability of a postsynaptic neuron after repeated low-frequency stimulation by a presynaptic neuron. A synapse is weakened when the presynaptic neuron is active and the postsynaptic dendritic spine is slightly depolarized or hyperpolarized, resulting in a small increase in intracellular calcium. LTD is mediated by the removal of AMPA receptors from the postsynaptic membranes of dendritic spines (Carlson, 2007).

LTP and LTD are two crucial mechanisms that underlie changes in neural architecture and synaptic transmission produced by both peripheral biofeedback and neurofeedback.


GABA is the most abundant and important inhibitory neurotransmitter in the brain. There are several types of GABA receptors, each of which produces inhibition in a different way. The ionotropic GABA-A receptor is a protein composed of five subunits that form an ion channel and contain binding sites that are specialized for different substances (GABA and benzodiazepines).

Caption: GABA is the major inhibitory neurotransmitter in the central nervous system. The GABA-A receptor is composed of five sub-units – two alpha, two beta, and one gamma sub-unit. Two molecules of GABA activate the receptor by binding to the alpha sub-units. Once activated, the receptor allows the passage of negatively-charged ions into the cytoplasm, which results in hyperpolarization and the inhibition of neurotransmission.

While the metabotropic GABA-B receptor is not well understood, research indicates that its activation reduces the release of many neurotransmitters and hormones (Wilson, 2003).

Caption: GABA is the main inhibitory neurotransmitter in the central nervous system (CNS). GABAergic inhibition is seen at all levels of the CNS, including the hypothalamus, hippocampus, cerebral cortex, and cerebellar cortex. As well as the large well-established GABA pathways, GABA interneurons are abundant in the brain, with 50% of the inhibitory synapses in the brain being GABA-mediated.

Anti-epileptic drugs suppress seizures by reducing repetitive firing or increasing GABAergic inhibition. Repetitive firing may initiate or maintain a seizure. Drugs slow firing by blocking sodium ion channels. Antiepileptic drugs enhance GABAergic inhibition by reducing GABA breakdown by transaminase, increasing chloride ion entry at GABA receptors or increasing GABA release from terminal buttons.

GABA-B receptors are G-protein-coupled metabotropic receptors. When valproic acid (Depakote) binds to these receptors in the amygdala, it stabilizes neuron membranes and inhibits neuron firing, which underlies seizure activity (Julien, 2005).


The monoamine neurotransmitters include dopamine, norepinephrine, and epinephrine (catecholamines) and serotonin (indoleamine). These neurotransmitters generally have modulating effects, altering the performance of diffuse networks of target neurons.


Dopamine exerts its postsynaptic effects on at least six receptors, which are all linked to G proteins. This means that dopamine functions as a neuromodulator. The two major families include D1 (D1 and D5) and D2 (D2A, D2B, D3, and D4).

Caption: There are two main subgroups of dopamine receptor – D1-like and D2-like. The D2-like family contains the D2, D3, and D4 subtypes and the D1-like receptor family contains the D1 and D5 receptor subtypes. The D2-like receptors are found throughout the brain and in smooth muscle and presynaptic nerve terminals. Coupled to inhibitory G-proteins, dopamine D2-like receptors have an inhibitory effect on neurotransmission when bound by an agonist. Many neuroleptic drugs are antagonists of the D2 receptors. This class of drug is used to treat psychotic disorders, such as schizophrenia.

Antipsychotic drugs blockade D2 receptors, and their effectiveness as D2-receptor antagonists are strongly correlated with their efficacy.

Caption: Dopamine is transmitted via three major pathways. The first extends from the substantia nigra to the caudate nucleus-putamen (neostriatum) and is concerned with sensory stimuli and movement. The second pathway projects from the ventral tegmentum to the mesolimbic forebrain and is thought to be associated with cognitive, reward, and emotional behavior. The third pathway, known as the tubero-infundibular system, is concerned with neuronal control of the hypothalamic endocrine system.

The nucleus accumbens (mesolimbic system) plays a critical role in reinforcement. Munro et al. (2006) reported that males released significantly more dopamine in the ventral striatum (which includes the nucleus accumbens) and in 3 of 4 other striatal (basal ganglia) sites than did women following intravenous injection of amphetamine. Males also rated amphetamine's effects more positively than did women. The sex difference in dopamine release at these sites could help explain why men experience a higher rate of drug addiction and disorders that involve these striatal regions (like Huntington's disease, obsessive- compulsive disorder, Parkinson's, and schizophrenia) than women.

Mesocortical neurons excite prefrontal cortical neurons that control working memory, planning, and strategy preparation for problem solving. Hypothalamic neurons that project to the pituitary may regulate endocrine hormones.

The substantia nigra projects to the basal ganglia (caudate nucleus and putamen) to control movement. The nigrostriatal pathway is progressively destroyed in Parkinson’s disease (Julien, 2005).


The dopamine D4 gene may play a role in ADHD. Patients with altered D4 genes are characterized by novelty-seeking and impulsivity (Disney et al., 1999). The anterior cingulate may be underactive or dysfunctional in ADHD patients resulting in abnormal selection of stimuli and responses (Bush et al., 1999).

Another hypothesis is that ADHD may involve subnormal norepinephrine transmission through the locus coeruleus branch of the ascending reticular activating system. In these cases, drugs like methylphenidate (Ritalin) may increase both locus coeruleus norepinephrine transmission and prefrontal cortical dopamine levels. The norepinephrine hypothesis is consistent with the success of catecholamine agonists, clonidine (Catapres) and guanfacine (Tenex), which may be combined with lower doses of methylphenidate (Ritalin) to increase treatment effectiveness.

Caron and Gainetdinov (1999) studied knockout mice lacking a dopamine transporter. The dopamine levels of these mice were five times higher than normal due to their inability to remove dopamine from the synapse, and their neurons fired more rapidly than normal. Like humans with ADHD, these mice showed hyperactivity, inattentiveness, and lack of impulse control in a novel environment.

Administration of fluoxetine (Prozac) dramatically reduced hyperactivity. This raised the possibility that ADHD may involve an imbalance between the dopamine and serotonin pathways, and that Ritalin may operate on the serotonergic raphe system. Antidepressants, including fluoxetine (Prozac), bupropion (Wellbutrin), and buspirone (BuSpar), have shown initial value in treating ADHD. BuSpar and Wellbutrin are especially prescribed in refractory ADHD cases (Julien, 2005).


Alcohol impacts on multiple transmitter systems, including acetylcholine, dopamine, GABA, glutamate, and serotonin receptors. Alcohol may affect the mesolimbic and mesocortical dopaminergic reinforcement pathways through action on GABA-A receptors, the ventral tegmental area, and the nucleus accumbens.

An abnormal form of the A1 allele, which results in defective D2 receptors, is present in most severe alcoholics. Reduced D2 receptor activity may produce a reward deficiency syndrome. Reduced activation of the nucleus accumbens and hypothalamus may produce dysphoria, drug craving, and compulsive drug-seeking and abuse (Blum et al., 1997). PET studies by Volkow and colleagues (1999) have linked abnormally low numbers of D2 receptors with craving for and abuse of cocaine and other psychostimulants.


Norepinephrine exerts postsynaptic effects at alpha and beta receptors, each of which has two subtypes. All norepinephrine receptors are G-protein linked.

Caption: There are two different types of adrenoreceptor – the α and β receptors. The α receptors are further classified into α1 and α2 subtypes, and the β receptors are further classified into β1, β2, and β3 subtypes. The α2 adrenoreceptors are widely distributed throughout the body and are found in adrenergic neurons, blood vessels, the pancreas, and in smooth muscle. Coupled to inhibitory G-proteins, α2 adrenoreceptors have an inhibitory effect on neurotransmission when bound by an agonist.

The cell bodies of noradrenergic neurons are located in seven regions of the pons and medulla, and one region of the thalamus. The cell bodies of the most important noradrenergic system are located in the locus coeruleus, a nucleus found in the dorsal pons. Axons project to the cerebral cortex, limbic system, hypothalamus, and cerebellum. They also travel to the dorsal horns of the spinal cord where they produce analgesia (Julien, 2005).

Caption: Many regions of the brain are supplied by the noradrenergic systems. The principal centers for noradrenergic neurons are the locus coeruleus and the caudal raphe nuclei. The ascending nerves of the locus coeruleus project to the frontal cortex, thalamus, hypothalamus, and limbic system. Norepinephrine is also transmitted from the locus coeruleus to the cerebellum. Nerves projecting from the caudal raphe nuclei ascend to the amygdala and descend to the midbrain.

Noradrenergic neurons are involved in analgesia, appetite, emotion, inhibition of REM sleep, positive feelings of reward, sexual behavior, thirst, and vigilance. Researchers have implicated norepinephrine in depression, PTSD, anxiety, and drug abstinence symptoms (Wilson, 2003).


Serotonergic cell bodies originate in nine clusters, most of which are found in the raphe nuclei of the midbrain, pons, and medulla. The two most important clusters are found in the dorsal and median raphe nuclei. Researchers have identified seven types of serotonin receptors with distinct distributions and functions.

Caption: There are four broad "superfamilies" of receptor: (1) the channel-linked (ionotropic) receptors; (2) the G-protein coupled (metabotropic) receptors; (3) the kinase-linked receptors; and (4) receptors that regulate gene transcription. The 5-HT1, 2, 4, 5, 6, and 7 receptors belong to the G-protein coupled superfamily. They are membrane receptors that have 7 transmembrane spanning α-helices. 5-HT binding to the "binding groove" on the extracellular portion of the receptor activates the G-proteins, which initiate secondary messenger signaling pathways. The downstream effect is either inhibitory or stimulatory, depending on the type of G-protein linked to the receptor. 5-HT1 receptors are linked to inhibitory G-proteins, whereas 5-HT2, 4, 6, and 7 are linked to stimulatory G-proteins.

Six of the seven are G-protein linked. 5-HT1 receptors appear to be involved in anxiety, aggression, and depression. 5-HT2 receptors help regulate appetite, motor control, and sexual function.

Caption: The principal centers for serotonergic neurons are the rostral and caudal raphe nuclei. From the rostral raphe nuclei, axons ascend to the cerebral cortex, limbic regions, and specifically to the basal ganglia. Serotonergic nuclei in the brainstem give rise to descending axons, some of which terminate in the medulla, while others descend the spinal cord.

5-HT3 receptors are implicated in nausea, vomiting, headache, anxiety, and schizophrenia. Dual-action antidepressants like nefazodone (Serzone) activate 5-HT1 receptors to produce antidepressant and anxiolytic effects, while they blockade 5-HT2 (agitation, restlessness, and sexual dysfunction) and 5-HT3 (nausea, headache, and vomiting) receptors.

While sleep regulation may be serotonin’s most important function, it also helps regulate vigilance, mood, carbohydrate appetite, and both gross movements and repetitive movements.

Jacobs and Fornal (1997, 1999) have shown that raphe neurons increase their firing during extrapyramidal torso and limb movements, and repetitive chewing and running movements. When they studied the brains of cats while they ran on a treadmill, they discovered that raphe neurons fired in step with their gait.

Serotonin inhibits impulsive and species-typical behavior. Researchers have reported low serotonin levels in suicidal individuals, and teenagers who shoplift—both impulsive behaviors. SSRIs are prescribed to treat both canine and human OCD-spectrum behaviors.

Dopamine, in contrast to serotonin, increases voluntary movement and mediates reinforcement. Serotonin receptors on endorphin-releasing neurons in the hypothalamus may increase the activity of dopaminergic reward pathways by inhibiting the release of GABA at cell bodies of the ventral tegmental area neurons (Wilson, 2003).


Acetylcholine binds to both nicotinic and muscarinic receptors. Nicotinic receptors are ionotropic, stimulated by nicotine, and blocked by curare. They are mainly found in the PNS on skeletal muscles. At CNS axoaxonic synapses, they produce presynaptic facilitation (increase neurotransmitter release). In the CNS, nicotinic receptors help regulate cortical blood flow, anxiety reduction, and decision making.

Caption: The nicotinic acetylcholine receptor is one of the main mediators of neurotransmission. This receptor is activated by the binding of two acetylcholine molecules. It is a ligand-gated ion channel, which permits the movement of positively-charged ions out of the synaptic cleft.

Muscarinic receptors are metabotropic, stimulated by muscarine, and blocked by atropine. Muscarinic receptors control smooth muscle and predominate in the CNS. In the CNS, muscarinic receptors help mediate learning, memory, attention, arousal, EEG, and postural control.

Caption: There are two main types of cholinergic receptors in the brain, muscarinic and nicotinic receptors. Muscarinic receptors are further classified as M1–M5 receptors, and nicotinic as NN and NM receptors. The muscarinic receptors are widely distributed throughout the central nervous system. Briefly, these receptors can be found in the cerebral cortex, corpus striatum, limbic system, thalamus, hypothalamus, midbrain, and brainstem. There is evidence to suggest that there is increased expression of cholinergic receptors in the brains of depressed people. Anticholinergic compounds are also reported to be mood elevating.

While Alzheimer’s disease has been associated with the early destruction of cholinergic neurons in the basal forebrain, Davis and colleagues (1999) have challenged this view. They reported that cholinergic deficits only appear in the late stages of Alzheimer’s, which raises questions about drug interventions designed to increase cholinergic transmission from the basal forebrain to the cerebral cortex and hippocampus.

The beta-amyloid hypothesis, illustrated below, is one of several competing explanations for Alzheimer's disease. Researchers are unsure whether amyloid plaques are causes of neuronal destruction or attempts to repair damage produced by unknown upstream disease processes.

If the early cognitive decline is due to injury to hippocampal circuitry that uses glutamate as a neurotransmitter, this suggests that early intervention should target different neurotransmitters and pathways (Julien, 2005).

Psychological trauma may cause dendrites with acetylcholine receptors to produce an abnormal form of acetylcholine esterase (AChE) called AChE-R, which may render them more excitable when stressed.

Ionotropic receptors contain a binding site for a ligand and an ion channel that opens when the neurotransmitter attaches to this site. These receptors operate rapidly and produce an effect that lasts from 1-100 ms. A nicotinic ACh receptor illustrates how ionotropic receptors operate.


Metabotropic receptors include all G-protein linked receptors, including autoreceptors. Neurotransmitters that bind to G-protein linked receptors are often called neuromodulators. Metabotropic receptors, which indirectly control the cell's operations, expend energy, and produce slower, longer-lasting, and more diverse changes than ionotropic receptors. Their effects can last several seconds, instead of milliseconds, because of the long-lived activity of G proteins and cyclic AMP. A norepinephrine receptor illustrates how metabotropic receptors operate (Wilson, 2003).

Transmitter binding activates G-proteins and may result in the synthesis of a second messenger that opens ion channels and/or modulates cellular functions like protein expression. A G-protein consists of alpha, beta, and gamma protein subunits that are associated with the neuron membrane and regulated by GDP and GTP (Fox, 2006). These receptors expend energy and produce slower, longer-lasting, and more diverse changes. When a ligand binds to a metabotropic receptor, the receptor changes shape and activates a G protein located inside the neuron.


An alpha-subunit of the G protein breaks away and may activate several enzymes within the neuron. A common target is adenylate cyclase, which transforms ATP into cyclic AMP, a second messenger. Cyclic AMP molecules move about the neuron, activating other enzymes. Protein kinase A, which controls the excitability of ion channels, is an important enzyme target of cyclic AMP. Cyclic AMP also travels to the nucleus where it can regulate gene expression.

Autoreceptors are metabotropic receptors that can be located on the membrane of any part of a neuron. They detect neurotransmitters released by a neuron, itself, and regulate internal processes like transmitter synthesis and release through G-proteins and the second messenger system. They bind with neurotransmitters released by the neuron, itself, and circulating drugs, and generate IPSPs that inhibit the neuron from reaching threshold. This phenomenon is called presynaptic inhibition and inhibits neurotransmitter synthesis and release (Wilson, 2003).

When cations (positive ions) like sodium enter a neuron, this depolarizes the cell. The membrane potential becomes more positive because the inside of the neuron is now more positive with respect to its outside. This brief positive shift in a postsynaptic neuron's potential is called an excitatory postsynaptic potential (EPSP). An EPSP pushes the neuron towards the threshold of excitation, when it can initiate an action potential. EPSPs are produced when neurotransmitters bind to receptors and cause positive, sodium ions to enter the cell.

When cations like potassium leave a neuron or anions (negative ions) like chloride enter a neuron, this hyperpolarizes the cell. The membrane potential becomes more negative since the inside of the neuron is more negative with respect to its outside. This brief negative shift in a postsynaptic neuron's potential is called an inhibitory postsynaptic potential (IPSP). An IPSP pushes the neuron away from the threshold of excitation (Wilson, 2003).

Integration is the addition of EPSPs and IPSPs at the axon hillock. Neurons sum EPSPs and IPSPs over their surface in spatial integration and over ms of time in temporal integration to raise the membrane from its resting potential to the threshold of excitation. EPSPS and IPSPs last from 15-200 ms, while action potentials take place in 1-2 ms.

Each EPSP depolarizes the axon hillock by about 0.5 mV due to the entry of positive sodium (Na+) ions. If there were no competing IPSPs, it would take about 30 EPSPs to trigger an action potential. If the summed EPSPs and IPSPs reach the threshold of excitation, 10-20 mV more positive than the resting potential (nominally –55 mV), Na+ channels in the axon hillock membrane are opened and an action potential is propagated down the axon (Wilson, 2003).

An action potential is a brief electrical impulse that transmits information from the axon hillock to the terminal button. Action potential transmission is described by the all-or-none law and rate law. The all-or-none law states that once an action potential is triggered in an axon, it is propagated, without decrement, to the end of the axon. The rate law states that neurons represent the intensity of a stimulus by variation in the rate of axon firing.


Small diameter, unmyelinated axons, transmit action potentials without weakening since sodium ion channels constantly regenerate this signal. This method is slow (35 m/s) because the signal travels in a step-by-step fashion, small segment by small segment, and waits for sodium channels to admit enough positive ions to reach the threshold of excitation. This method also consumes considerable energy, since sodium-potassium transporters, powered by ATP, are located all along the axon membrane to exchange 3 sodium for 2 potassium ions.

Medium-to-large diameter, myelinated axons, transmit action potentials using a method called saltatory conduction. The action potential weakens under each myelinated segment (cable properties) and then is regenerated at each node of Ranvier. Each segment of insulating myelin is almost 1 mm long. The gaps between segments, which are called nodes of Ranvier, are 1 to 2 thousandths of a millimeter.


This method is about 200 times faster (120 m/s) than transmission in unmyelinated axons because the action potential jumps from node to node, in 1 mm steps, instead of steps that are a thousand times smaller. Myelination' s effect on transmission speed is equivalent to increasing an axon's diameter 100 times! This method is also more energy efficient because sodium-potassium transporters are only needed at the nodes of Ranvier, where ion exchange is possible. These transporters account for about 40% of a neuron’s energy expenditure (Garrett, 2003).

Electrical synapses communicate information across gap junctions between adjacent membranes using ions.

Electrical synapses are symmetrical. Ions flow across the gap junction into the more negatively-charged neuron, as long as the gap junction remains open. This means that whether neurons are presynaptic or postsynaptic depends on their respective charges.

Transmission across electrical synapses is instantaneous, compared with the 10 ms or longer delay in chemical synapses. The rapid information transmission that characterizes electrical synapses enables large circuits of distant neurons to synchronize their activity and simultaneously fire. Astrocytes communicate with each other, and with neurons using gap junctions.

Neurons that secrete hormones use electrical synapses to simultaneously release their chemical messengers. Neonatal brains may use gap junctions to activate many neurons at once (Wilson, 2003). This may be a preliminary step toward the development of chemical synapses between these neurons, which will eventually replace their electrical synapses (Lustig, 1994).

Landisman and Connors (2005) challenged the traditional view that electrical synapses are inflexible. They demonstrated that activation of metabotropic glutamate receptors (mGluR) can modulate connexin36 gap junctions in mammalian interneurons located in the dorsal thalamus. Activation of these receptors reduces neuronal transmission by 20-50%, which is analogous to the long-term depression (LTD) observed in chemical synapses. This inhibitory process may allow thalamic relay cells to increase attention to sensory stimuli when mammals are alert and explore their environment. The authors also speculate that long-term potentiation (LTP), which increases neuronal communication, may also occur at mammalian electrical synapses.

Chemical synapses
transmit molecules across gaps of less than 300 angstroms. Neurons use chemical synapses to produce short-duration (ms) and long-duration (seconds to hours) changes in the nervous system. Chemical synapses are capable of more extensive communication, and of producing more diverse and long-lasting changes, than electrical synapses.

These synapses are functionally and structurally asymmetrical. They are functionally asymmetrical because the presynaptic neuron sends a chemical message and the postsynaptic neuron receives it. They are structurally asymmetrical because the presynaptic element (axon) contains vesicles containing neurotransmitter and the postsynaptic element (dendrite) does not.

Chemical synapses release a growing roster of chemical messengers. Contrary to Dale’s principle, a neuron can release more than one neurotransmitter, often two to four. The same terminal button can actually release fast and slow neurotransmitters, two fast neurotransmitters, excitatory and inhibitory neurotransmitters, or different neurotransmitters at different branches of the same axon (Wilson, 2003).

Not only can chemical synapses release a large combination of neurotransmitters, these chemical messengers can target diverse populations of receptors located in different regions of the nervous system. There may be as many as 1,000 different types of receptors on CNS and PNS neurons (Wilson, 2003). Neurotransmitters and drugs do not have intrinsic effects. Their effects depend on their interaction with their targets (Julien, 2005).

The possible combinations of neurotransmitters, receptors, receptor locations endow chemical synapses with a complex language required by the nervous system’s sensory, motor, and associative functions.

The process of neurotransmitter release is called exocytosis. When an action potential arrives and depolarizes the terminal button, calcium ions enter the terminal button from the extracellular fluid and calcium binds with clusters of protein molecules that join the vesicles with the presynaptic membrane. The clusters move apart, forming a hole through both membranes called a fusion pore, and neurotransmitter leaves the terminal button for the synaptic cleft or extracellular fluid.

Neurotransmitter release also occurs outside of the synaptic cleft. Neurotransmitters can be released from dendrites, the terminal button, and axonal varicosities (swellings in an axon) into the extracellular space. This extrasynaptic release is called volume transmission.

Norepinephrine is primarily released from axonal varicosities via volume transmission. In the dorsal raphe nucleus, thin axons may release serotonin from “spindle-shaped varicosities” via volume transmission. In contrast, the thick axons of the median raphe nucleus release serotonin from bead-like varicosities, which form synapses (Carlson, 2007).

Reuptake is the primary method that neurons terminate the action of neurotransmitters. Reuptake transporters located in terminal buttons and astrocytes remove neurotransmitters from the synaptic cleft.

Caption: The action of 5-HT at the synapse is terminated by its reuptake across the presynaptic membrane. This is an energy-dependent process. Sodium/potassium ATPases use energy from ATP hydrolysis to create a concentration gradient of ions across the presynaptic membrane that drives the opening of the transporter and co-transport of sodium and chloride ions and 5-HT from the synaptic cleft. Potassium ions binding to the transporter enable it to return to the outward position. Release of the potassium ions into the synaptic cleft equilibrates the ionic gradient across the pre-synaptic membrane. The 5-HT reuptake transporter is then available to bind another 5-HT molecule for reuptake.

Serotonin-specific reuptake inhibitors (SSRIs) produce antidepressant effects by interfering with this process. Bupropion (Wellbutrin, Zyban), cocaine, amphetamine, and methylphenidate (Ritalin) block dopamine uptake.

In enzymatic deactivation, an enzyme breaks the neurotransmitter apart into inactive fragments. For example, acetylcholine transmission is ended by the enzyme acetylcholine esterase (AChE). Deactivating enzymes, which are located in the synaptic cleft, degrade a neurotransmitter molecule when it detaches from its binding site.

Caption: Cholinergic nerve transmission is terminated by the enzyme acetylcholinesterase (AChE). AChE is found both on the post-synaptic membrane of cholinergic synapses and in other tissues (e.g., red blood cells). Acetylcholine (ACh) binds to AChE and is hydrolyzed to acetate and choline. This inactivates the ACh and the nerve impulse is halted. AChE inhibitors (e.g., rivastigmine) prevent the hydrolysis of ACh, which increases the concentration of ACh in the synaptic cleft. AChE inhibitors are widely used in the treatment of Alzheimer’s disease and myasthenia gravis.

Metrifonate produces long-lasting inhibition of AChE, which may slow the cognitive decline of mild-to-moderate Alzheimer’s patients.

Degrading enzymes like MAO and COMT are also found in the terminal button, where they prevent excessive neurotransmitter release. Neurotransmitters that have been pumped back into the terminal button, and not yet not returned to protective vesicles, may be destroyed by these enzymes.

MAO targets the monoamines dopamine, norepinephrine, and serotonin. MAO inhibitors increase monoamine availability in an effort to treat clinical depression. COMT only targets the catecholamines dopamine and norepinephrine.

The electroencephalogram (EEG) is the voltage difference between at least two electrodes, where at least one electrode is located on the scalp or inside the brain. The EEG is a recording of both EPSPs and IPSPs that occur largely in dendrites in pyramidal cells located in macrocolumns, several mm in diameter, in the upper cortical layers (Fisch, 1999).

Caption: Tonic-clonic generalized seizures affect the whole brain and produce abnormal electrical activity at the frontal, temporal, and occipital sites. A tonic-clonic seizure is typified by an initial strong contraction of the whole musculature, causing a rigid extensor spasm. This "tonic" phase is followed by a series of synchronous jerks, the "clonic" phase. The patient remains unconscious for a few more minutes (post-convulsive coma), before gradually recovering.

The cortex is the outermost layer covering the cerebral hemispheres, and consists of glia and unmyelinated parts of a neuron like the soma, dendrites, and axons.

Caption: This image illustrates the brain from the left side and indicates the following cortical areas and the hippocampus with different colors. Broca's area (yellow), the premotor cortex (red), primary motor cortex (blue), primary auditory cortex (orange), angular gyrus (purple), the hippocampus (pink), and occipital lobes (green) are depicted.

A cortical pyramidal neuron is cylindrical with a cell body that resembles a pyramid. An apical dendrite arises from the apex of the pyramid and extends vertically to layer 1 of the neocortex. Multiple basal dendrites branch out horizontally from the 30 μm base of the pyramid through the layer where the neuron resides. The axon that leaves the cell body may form local connections, and then project to sites in the cerebral cortex or elsewhere in the brain, including the spinal cord. Cortical output layers 5 and 6 contain the most pyramidal neurons (Winn, 2001).


Macrocolumns of pyramidal cells create extracellular dipole layers, parallel to the surface of the cortex, which send opposite charges towards the surface and the deepest of the 5-7 layers of cortical neurons.  A sink is where current enters the neuron. Positive sodium ion entry into a neuron creates an active sink, represented by -ve. Since the sink involves the entry of positive ions into the dendrite, the extracellular area surrounding the sink becomes electrically negative. The source is the place at the other end of the neuron where current leaves, and is represented by +ve. The extracellular area surrounding the source becomes electrically positive. A dipole is the electrical field generated between the sink and the source, which may be located anywhere along the dendrite.

The parallel alignment of the pyramidal cells allows the thalamus to synchronize the depolarization and hyperpolarization of thousands of these neurons to produce a current that can be detected from the scalp. The thalamus generates theta, alpha, and sensorimotor rhythms by orchestrating simultaneous excitatory or inhibitory postsynaptic potentials at pyramidal cell dendrites within the same macrocolumn.


Thalamic activation of pyramidal neurons produces a detectable current because the pyramidal neurons are all aligned with the cortical surface, the postsynaptic potentials at cells within the same macrocolumn add together because they have the same positive or negative charge, and the macrocolumns fire synchronously. Stimulation of the portion of the dendrite closest to the scalp produces a small negative current at the scalp and an upward deflection in the EEG. Stimulation of the region of the dendrite closest to the cell body produces a small positive current at the scalp and a downward deflection in the EEG (Thompson & Thompson, 2003).

Below is a BioGraph ® Infiniti EEG display with electrodes at Cz, A1, and A2.

Sensory input produced by activities like reading a novel and listening to music can desynchronize cortical activity resulting in lower-amplitude, higher-frequency EEG waveforms (Neumann, Strehl, & Birbaumer, 2003). Arousal and specific forms of cognitive activity may reduce alpha amplitude or eliminate it entirely, a phenomenon called alpha blocking, while increasing EEG power in the beta range (Andreassi, 2007).

The classical routes for EEG activation consist of specific sensory pathways like the visual (retina to the visual cortex), auditory (cochlea to the auditory cortex), and somatosensory (chemoreceptors and mechanoreceptors to the somatosensory cortex) systems (Galambos, Myers, & Sheatz, 1961). Increased transmission of information through these pathways desynchronizes EEG activity in the cortical regions to which these afferent neurons project, as specialized circuits of neurons independently process this information. Afferent neurons also distribute information along a more medial (midline) route through the ascending reticular formation.

The reticular formation is a network of 90 nuclei within the central brainstem from the lower medulla to the upper midbrain. The reticular formation sends axons to the spinal cord, thalamus, and cortex where it contributes to diverse functions like neurological reflexes, muscle tone and movement, and attention, arousal, and sleep.

Arousal, which combines alertness and wakefulness, is produced by at least five neurotransmitters, including acetylcholine, histamine, hypocretin, norepinephrine, and serotonin. Acetylcholine (ACh) is crucial to cortical arousal and cholinergic neurons in the pons (found in the brainstem) comprise an important component of the ascending reticular activating system. Electrical stimulation of the dorsal pons activates the cerebral cortex and increases ACh release 350% through recruitment of cholinergic neurons in the basal forebrain (diverse structures located below the basal ganglia in the anterior brain). Cholinergic neurons in the medial septum regulates hippocampal activity, which is crucial to declarative memory (Carlson, 2007).

Controversy continues regarding the generators of slow cortical potentials and fast-wave EEG activity detected at the scalp. Steriade (2005) has cautioned that categorizing EEG rhythms by their frequency range can be deceptive. A comprehensive explanation of EEG rhythms requires that we identify their behavioral context and the intracellular activity that produces them. Animal intracellular recording and human EEG monitoring support the existence of a "unified corticothalamic network that generates diverse types of brain rhythms grouped by the cortical slow oscillations" (p. 76).

Slow cortical potentials have been identified in cortical neurons, the thalamus, and glial cells. Cortical neurons in layers II to VI generate slow oscillations when the thalamus is removed or when cortical tissue is studied in vitro (in an artificial environment) or in vivo (within a living organism). Thalamic reticular neurons exhibit similar slow spontaneous oscillations when studied in vitro and synchronized intracortical oscillations may depend on a corticothalamic network that targets these thalamic neurons. Slow oscillations with longer oscillatory cycles than cortical neurons have also been observed in glial cells. Glial cells, which are shown below, may influence the timing of neuronal oscillation through their control of K+ outflow (Steriade, 2005).

The thalamus is a structure above the hypothalamus that receives, filters, and distributes most sensory information. The thalamus contains neurons that can block or relay ascending sensory information. When these thalamic neurons rhythmically fire, this blocks transmission of information to the cortex. When they depolarize in response to sensory information, this integrates and transmits this information to the cortex. Inputs to the thalamus determine whether these neurons block or relay sensory information (Abarbanel, 2001).

Caption: This image illustrates the limbic system in the brain from a three-quarter superior view of the cerebrum. Cortical areas are semi-transparent so as to show the limbic system deep within the brain. Structures include the thalamus (purple), hypothalamus (salmon), hippocampus (red), and amygdala (tan).

There are actually two delta rhythms, a slow oscillation under 1 Hz and traditional 1-4 Hz oscillations. The slow 0.3-0.4 Hz oscillation originates in the neocortex and persists when the thalamus is removed. Thalamocortical neurons generate the 1-4 Hz oscillations observed during human stage 3 and 4 sleep. Slow neocortical oscillations may synchronize the thalamic delta rhythm (Steriade, 2005).

The 4-7 Hz theta rhythm may be generated a cholinergic septohippocampal system that receives input from the ascending reticular formation and a noncholinergic system that originates in the entorhinal cortex, which corresponds to Brodmann areas 28 and 34 at the caudal region of the temporal lobe (Steriade, 2005).

The 8-13 Hz alpha rhythm differs from spindle waves in both its source and the activity during which it is observed. Based on experimental studies in dogs, Lopes da Silva et al. (1980) concluded that alpha activity is primarily spread by an intracortical network that lies parallel to the cortical surface and that there is only a moderate contribution from neurons in the lateral geniculate nucleus of the thalamus that project to the cortex. Researchers have correlated the alpha rhythm with "relaxed wakefulness." Spindle waves, in contrast, originate in the thalamus and occur during unconsciousness and stage II sleep (Steriade, 2005).

Fast 20-50 Hz beta rhythms associated with arousal and attention are generated by brainstem mesencephalic reticular stimulation that depolarizes neurons in both the thalamus and cortex. The 40-Hz rhythm, which has been associated with feature binding (linking an apple's color to its shape), has been attributed to the neocortex and thalamocortical neurons. The 40-Hz rhythm may be generated by intracortical circuits, thalamocortical circuits, and synapses within other subcortical regions, and by interactive connections between distant brain regions (Steriade, 2005).


Sterman (1996) proposed that vigilance, sensorimotor integration, and cognitive integration systems mainly influence thalamic generation of electrical potentials.

The vigilance system consists of both specific brainstem nuclei (e.g., locus coeruleus and raphe nuclei), and their diffuse connections with the thalamus and other subcortical structures, and the cortex. Several neurotransmitter systems mediate vigilance, including cholinergic/glutamatergic (reticular formation), noradrenergic (locus coeruleus), and serotonergic (raphe) neurons.

The sensorimotor system includes ascending pathways that convey information about touch and proprioception to the thalamus, the thalamus and its thalamic projections to the sensorimotor cortex, and the sensorimotor cortex, and its efferent fibers.

The cognitive integration system consists of centers that analyze and integrate sensory information with motor activity.

Sterman (2000) hypothesized that increased inhibition of the thalamus by the substantia nigra using two parallel pathways may generate the theta rhythm.

The presence or absence of input from these three systems influence the rhythm produced by generators in the thalamus. Withdrawal of cognitive integration input results in the alpha rhythm. Withdrawal of sensorimotor input produces the SMR rhythm. Withdrawal of vigilance input generates the theta rhythm.

Sieb (1990) proposed that the ascending sensory information--processed by the brainstem and transmitted to the thalamus--also activates septal nuclei and the hippocampus of the limbic system, and the prefrontal cortex. To focus attention on high-priority environmental signals, the hippocampus generates a theta rhythm that inhibits circuits responsible for "orientation, alertness, awareness, and arousal." The prefrontal cortex responds to inputs concerning the high-priority environmental signals by signaling the septal nuclei, which induce a beta rhythm in the hippocampus to remove its inhibition of the vigilance centers (Abarbanel, 2001).

Electroencephalographers, professionals who study the EEG, divide the EEG into frequency bands including slow cortical potentials, delta, theta, alpha, sensorimotor rhythm, beta, and gamma.

EEG rhythms possess frequency and amplitude. Frequency is the number of cycles completed each second. The higher the frequency, the shorter the wavelength. Amplitude is the energy or power contained within the EEG signal and is measured in microvolts or picowatts. High amplitude means that a large number of neurons are depolarizing and hyperpolarizing at the same time.


Slow cortical potentials (SCPs) are gradual changes in the membrane potentials of cortical dendrites that last from 300 ms to several seconds. These potentials include the contingent negative variation (CNV), readiness potential, movement-related potentials (MRPs), and P300 and N400 potentials.

SCPs modulate the firing rate of cortical pyramidal neurons by exciting or inhibiting their apical dendrites. They group the classical EEG rhythms using these synchronizing mechanisms (Steriade, 2005). Negative SCPs are produced by synchronous EPSPs at the apical dendrites and increase the probability of neuron firing. Positive SCPs are generated by IPSPs at the apical dendrites and decrease the probability of neuron firing.

The computer model below depicts terminal buttons (light green) forming synapses on a dendrite (dark green) to generate the EPSPs and IPSPs that create SCPs.


The contingent negative variation (CNV) is a steady, negative shift in potential (15 microvolts in young adults) detected at the vertex. This slow cortical potential may reflect expectancy, motivation, intention to act, or attention. The CNV appears 200-400 ms after a warning signal (S1), peaks within 400-900 ms, and sharply declines after a second stimulus that requires performance of a response (S2).


The readiness potential is a slow-rising, negative potential (10-15 microvolts) detected at the vertex before voluntary and spontaneous movement. This slow cortical potential precedes voluntary movement by 0.5 to 1 second and peaks when the subject responds. This potential is separate from the CNV (Stern, Ray, & Quigley, 2001).


Movement-related potentials (MRPs) occur at 1 second as subjects prepare for unilateral voluntary movements. MRPs are distributed bilaterally with maximum amplitude at Cz. The supplementary motor area and primary motor and somatosensory cortices primarily generate these potentials (Babiloni et al., 2002).

P300 and N400 ERPs are classified as long-latency potentials due to their extended latencies following stimulus onset.

The P300 potential is an event-related potential (ERP) with a 300-900 ms latency and greatest positive peaks located over parietal lobe sites. Researchers elicit the P300 potential by exposing subjects to an odd-ball stimulus, a meaningful stimulus that is different from others in a series (a colored playing card presented in a series of monochrome cards). The P300 potential may reflect an event’s subjective probability, meaning, and transmission of information. Research shows this is separate from the contingent negative variation (CNV) (Stern, Ray, & Quigley, 2001).

Shorter P300 latencies may reflect better allocation of attention, and researchers have measured longer P300 latencies in ADD than non-ADD samples. Experimental subjects show longer latencies when lying than when telling the truth (Farwell & Donchin, 1991; Thompson & Thompson, 2003).

The N400 potential is an event-related potential (ERP) elicited when we encounter semantic violations like ending a sentence with a semantically incongruent word ("The handsome prince married the beautiful fish"), or when the second word of a pair is unrelated to the first (BATTLE/GIRL). Warren and McIlvane (1998) speculate that the N400 potential is evoked whenever a general conceptual system that produces category judgments encounters a mismatch that violates equivalence relations. Halgren and colleagues (2002) consider it an index of the difficulty of semantic processing.


Event-related potentials (ERPs) are changes in brain activity in response to specific stimuli. Investigators detect ERPs using electrodes placed along the midline (Fz, Cz, and Pz). A computer analyzes a subject's EEG responses to the same stimulus or task over many trials to subtract random EEG activity. ERPs always have the same waveform morphology. Their negative and positive peaks occur at stable intervals following the stimulus.

Sensory ERPs are evoked by external sensory stimuli (auditory, olfactory, somatosensory, and visual). These evoked potentials or exogenous ERPs have a negative peak 80-90 ms and positive peak about 170 ms following stimulus onset. The orienting response ("What is it?") is a sensory ERP. The N1-P2 complex in the auditory cortex of the temporal cortex reveals whether an uncommunicative person can hear a stimulus.

Motor ERPs are detected over the primary motor cortex (precentral gyrus) during movement and their amplitude is proportional to the force and rate of skeletal muscle contraction (Thompson & Thompson, 2003).

Fast cortical potentials range from 0.5 Hz-100 Hz. The main frequency ranges include delta, theta, alpha, sensorimotor rhythm, and beta. As you already realize, researchers use varying cutoffs to detect fast cortical potentials. You will see slightly different bandpasses reported throughout this unit as we attempt to be faithful to cited references. Remember that bandpass is only one characteristic of EEG activity. We also have to consider factors like waveform shape, sensor placement, and behavioral context.

The delta rhythm ranges from 0.5-3.5 Hz with 20-200 microvolt synchronous waves. Microvolt means millionth of a volt. Synchronous means that groups of neurons depolarize and hyperpolarize at the same time.


The delta rhythm represents "idling activity" during which information is not actively processed. The greatest amplitude or signal strength is found in the central region of the scalp. The delta rhythm is the dominant frequency from ages 1-2 and is associated in adults with deep sleep and brain pathology like trauma and tumors, and learning disability (Hugdahl, 1995; Thompson & Thompson, 2003).

John S. Anderson has generously provided a NeXus-32 19-channel recording. This is a linked-ears record of a young adult male. The record is digitally filtered to only display the 1-4 Hz delta portion of the raw signal. Note two significant eye movement artifacts at the end of the record.


The theta rhythm ranges from 4-8 Hz with 20-100 microvolts. This rhythm also may represent "idling activity." The greatest amplitude is found in the frontal and temporal regions of the scalp. Since there may be several theta generators, the theta rhythm is associated with different behavioral processes. The theta rhythm is associated with drowsiness or starting to sleep, REM sleep, hypnagogic imagery (intense imagery experienced before the onset of sleep), and hypnosis.


Schacter (1977) has proposed that there are two types of theta activity; one associated with drowsiness and the inattention observed in ADHD, and another when we effectively process cognitive and perceptual information.

The theta rhythm is the dominant frequency in healthy young children (Thompson & Thompson, 2003). Theta amplitudes and normative theta-to-beta ratios are higher in children than older adults. Children diagnosed with ADHD often have higher ratios than children without ADHD. Theta-to-beta ratios greater than 3:1 may indicate a slow-wave disorder and children with a slow-wave disorder may have ratios as high as 6:1 (Demos, 2005).

John S. Anderson has generously provided a NeXus-32 19-channel recording. This is a digitally-filtered record showing only 4-8 Hz theta activity of an eyes-closed awake record of a young adult male. The record shows the beginnings of drowsiness with increased theta amplitudes occurring more and more frequently.


The alpha rhythm ranges from 8-13 Hz with 20-60 microvolt synchronous waves. Alpha is defined by its waveform and not by its frequency. For example, a sinusoidal alpha waveform in children may occur at 7 Hz. Alpha is an "idling frequency" that is produced when pools of thalamic neurons fire synchronously. Frontal and occipital alpha are produced by separate generators.


Alpha activity can be observed in about 75% of awake, relaxed individuals. Alpha amplitude is highest in the occipital region and decreases toward the frontal region where it is the lowest. Higher peak alpha frequencies may be healthier because they represent faster processing speeds. Peak frequencies slow with age and specific medication. The alpha rhythm is replaced by low-amplitude desynchronized beta activity during movement, complex problem-solving, and visual focusing. This phenomenon is called alpha blocking (Hugdahl, 1995; Thompson & Thompson, 2003).

John S. Anderson has generously provided a NeXus-32 19-channel recording. This is digitally-filtered record showing only 8-11 Hz alpha activity of an eyes closed awake record of a 12-year-old male. Note that alpha activity is primarily detected by the occipital and parietal sensors, with "blocking" of alpha when the client opens his eyes in the last 3 seconds of the record.

The sensorimotor rhythm (SMR) ranges from 12-15 Hz and is located over the sensorimotor cortex (central sulcus). The waves are synchronous. The sensorimotor rhythm is associated with the inhibition of movement and reduced muscle tone. The SMR is generated by "ventrobasal relay cells in the thalamus and thalamo-cortical feedback loops" (Thompson & Thompson, 2003).


The beta rhythm exceeds 13 Hz with 2-20 microvolts asynchronous waves. Asynchronous means the neurons depolarize and hyperpolarize independently. The beta rhythm is distributed across the scalp with the highest amplitude in the frontal and precentral areas. This rhythm is produced when processing new sensory information overrides the thalamic pacemakers (Andreassi, 2000). The beta rhythm can be divided into two ranges (13-21 Hz and 20-32 Hz).


EEG activity from 36-44 Hz is also referred to as gamma (DePascalis & Ray, 1998). Gamma activity changes when subjects learn to perceive meaningful patterns, like a Dalmatian concealed by a black and white background (Tallon-Baudry et al., 1997).


The majority of EEG power or signal energy falls within the 0-20 Hz frequency range. You may recall that hertz (Hz) is an abbreviation for cycles per second. The dominant frequency (frequency with the greatest amplitude) during an adult's waking consciousness is at least 13 Hz.


Thompson and Thompson (2003) observed that delta is dominant below age 3, theta from 3 to 5, and low alpha from 6 to 8. Alpha frequency increases to a peak around 10 Hz after age 10. Peak frequencies slow during adulthood with aging.

Waveform refers the morphology or shape of an EEG wave. A single wave or successive waves are termed EEG activity.

Regular or monomorphic waves are successive waves with identical shapes. Regular waves may resemble sine waves (sinusoidal) or may be arched (resembling wickets) or saw-toothed (asymmetrical and triangular).

Irregular waves are successive waves that constantly alter their shape and duration.

A monophasic wave consists of either a single negative (upward) or positive (downward) deflection from baseline. A diphasic wave contains both a negative and positive deflection from baseline. A triphasic wave contains three deflections from baseline. A polyphasic or multiphasic wave contains two or more deflections of opposite polarity from baseline.

A transient is a single wave or sequence of regular waves, called a complex, distinguishable from background EEG activity. A spike is a negative transient with a pointed peak at conventional paper speeds, 20-70 ms duration, and 40-100 μV amplitude. Sharp waves resemble spikes with a pointed peak at conventional paper speeds, but their 70-200 ms duration is longer. Sharp transients contain several sharp waves. Complexes containing sequences of spikes and sharp waves may indicate epileptiform activity. A spike-and-slow-wave complex consists of a spike followed by a  higher amplitude slow wave at 3 Hz. In an absence seizure, the amplitudes are very high (e.g., 160 μV). A multiple spike-and-slow-wave complex consists of multiple spikes associated with at least one slow wave.

Lambda waves are saw-toothed transient waves from 20-50 μV in amplitude and 100-250 ms in duration detected over the occipital cortex during wakefulness. These positive deflections are time-locked to saccadic movements and observed during visual scanning, as during reading.

The mu rhythm consists of arch-shaped waves that range from 7-11 Hz with amplitudes typically below 50 μV that are detected over Cz and Pz in waking subjects. These waves are seen in the healthy EEG records of 7% of the population. While these waves resemble alpha, they contain sharp positive transients and curved negative segments. Mu waves are blocked or reduced by exposure to a tactile stimulus, planning to move, readiness to move, or moving a contralateral limb (making a fist). Clinicians should discriminate between mu and central alpha, which may be an ADHD marker. When mu is only detected in one hemisphere, this may indicate pathology.

The kappa rhythm is comprised of bursts of alpha or theta and is detected over the temporal lobes of subjects during cognitive activity (Bromfield, 2002; Fisch, 1999; Thompson & Thompson, 2003).

Generalized EEG waves occur during the same epoch in most EEG channels. Lateralized waves are primarily detected on one side of the scalp and may indicate pathology. Focal waves are detected within a limited area of the scalp, cerebral cortex, or brain (Fisch, 1999).

Thompson and Thompson (2003) observed that alpha amplitude is typically higher in the right hemisphere than the left and that the amplitude difference between the hemispheres should not be greater than 1.5 times.

The alpha rhythm should exceed 8 Hz. Failure to exceed 8 Hz suggests pathology, and if there is a 1-Hz difference in the dominant alpha rhythm between both hemispheres, there may be pathology in the hemisphere with slower alpha.

Since alpha is primarily detected at occipital sites, predominant frontal and central alpha is abnormal. Prefrontal alpha often represents artifact due to eye movement.

Beta asymmetry should be no greater than 35% of the amplitude detected at the higher amplitude hemisphere. When beta asymmetry exceeds 35%, the hemisphere with lower beta amplitude should be examined for pathology.

Localized slow waves may indicate a transient ischemic attack (TIA) or stroke, migraine, mild head injury, or tumors above the tentorium. Deep lesions result in bilateral or unilateral delta.

Bilateral synchronous slow waves are observed in drowsy children. When detected in alert adults, intermittent bursts of high amplitude slow waves may be a sign of gray matter lesions in deep midline structures.

Generalized asynchronous slow waves are seen in sleepy children and those with elevated temperatures. In adults, this may indicate degenerative disease, dementia, encephalopathy, head injury, high fever, migraine, and Parkinson's disease.

Continuous irregular delta is produced by white matter lesions seen in disorders like multiple sclerosis (Thompson & Thompson, 2003)

When performing mental arithmetic with eyes closed, reduced alpha amplitude in one hemisphere may signal damage to the ipsilateral parietal or temporal lobe. When a client opens her eyes, the absence of alpha blocking (Bancaud's phenomenon) may indicate a lesion of the parietal or occipital lobes.

Anxiety, and metabolic and toxic disorders can produce a bilateral reduction in alpha. There may be a localized reduction in alpha for minutes after a focal seizure. Head trauma may slow alpha.

Alpha asymmetry must exceed 50% to be classified as abnormal (Thompson & Thompson, 2003).

An isolated reduction in beta indicates a focal lesion. Beta asymmetry exceeding 35% indicates pathology in the hemisphere with less beta. A migraine can decrease beta. There may be a localized reduction in beta for minutes after a focal seizure. CNS depressants produce a generalized increase in beta (Thompson & Thompson, 2003).

Networks of neurons generating the EEG activity at different sites can produce signals that are identical in amplitude, frequency, and phase, or that are completely unrelated.

Synchrony means that the firing of pools of neurons is coordinated. EEG signals can display local synchrony, frequency synchrony, and phase synchrony.

The two BioTrace+ /NeXus-10 graphs below show alpha activity. The upper graph shows an alpha waveform with regular bursts of alpha activity, often called alpha spindles. The lower graph shows alpha amplitude. Note the different time (X-axis) and microvolt (Y-axis) scales for each graph. This movie was generously provided by John S. Anderson.

Local synchrony
occurs when high-amplitude EEG signals are produced by the coordinated firing of cortical neurons. For example, an alpha amplitude of 20-60 microvolts detected at O1-A1 is produced by the synchronous firing of pools of neurons. The amplitude of beta activity at this site is lower due to desynchronized firing. This is analogous to the volume generated by a choir. When performers sing in unison, they produce a louder sound than when they sing separately.

Frequency synchrony occurs when identical EEG frequencies are detected at two or more electrode sites. For example, 12 Hz may be simultaneously detected at O1-A1 and O2-A2.

Phase refers to the degree to which the peaks and valleys of EEG waveforms coincide. The waveforms shown below are 90 degrees out of phase.


Phase synchrony occurs when identical EEG frequencies are detected at two or more electrode sites and the peaks and valleys of the EEG waveforms coincide. This is also called global synchrony. For example, EEG training may aim at producing phase-synchronous 12-Hz alpha waves at O1-A1 and O2-A2.

Neuroanatomists describe directions with respect to the neuroaxis, which is an imaginary line that runs centrally through the central nervous system (CNS) from the front of the prefrontal cortex to the base of the spinal cord.

The following terms are used to designate directions in the central nervous system. Anterior means near or toward the front of the head. Rostral is "toward the beak" and also means toward the front of the head. Posterior means near or toward the back of the head. Caudal is "toward the tail" and means away from the front of the head. Dorsal is "toward the back" and means toward the upper back or head. Ventral is "toward the belly" and means toward the base of the skull or front of the body. Lateral means to the side, away from the center, as in the lateral geniculate nucleus. Medial means toward the center of the body, away from the side, as in the medial geniculate nucleus.

refers to structures that are located on the same side of the body, for example, the left olfactory bulb distributes axons to left hemisphere. Contralateral refers to structures that are located on opposite sides of the body. For example, neurons in the left primary motor cortex control muscles on the right side of the body.

The cerebral cortex is the layer of gray matter that covers the cerebral hemispheres. The cerebral cortex consists of gray matter and white matter.

Gray (or grey) matter
, which looks grayish brown, is comprised of cell bodies, dendrites, unmyelinated axons, glial cells, and capillaries. White matter gains its opaque white color from myelinated axons.

The convolutions of the cerebral cortex contain two-thirds of its surface area and maximize the volume of cortical tissue housed within the skull. Cerebral cortical convolutions include sulci, which are shallow grooves in the surface of the cerebral hemisphere (central sulcus), fissures, which are deep grooves (lateral fissure), and gyri, which are ridges of cortex demarcated by sulci or fissures (precentral gyrus) (Carlson, 2007).

The cerebral cortex consists of six layers 3 mm thick with a surface area of about 2360 cm2 with white matter underneath. Layers I-III receive afferent corticocortical fibers that connect the left and right hemispheres. Layer III is the main source of efferent corticocortical fibers. Layer IV is the primary destination of thalamocortical afferents and intra-hemispheric corticocortical afferents. Layer V is the primary origin of efferent fibers that target subcortical structures that have motor functions. Layer VI projects corticothalamic efferent fibers to the thalamus, which together with the thalamocortical afferents, creates a dynamic and reciprocal relationship between these two structures (Creutzfeldt, 1995).

Each cerebral hemisphere is divided into frontal, parietal, temporal, and occipital lobes as shown below.

The frontal lobes are divided into the motor cortex, premotor cortex, and prefrontal cortex. The motor cortex is located in the precentral gyrus and guides fine motor coordination (like writing). The premotor cortex is anterior to the motor cortex and helps program head, trunk, and limb movements.

The prefrontal cortex is the most anterior frontal lobe division and is subdivided into dorsolateral, medial, orbitofrontal, and anterior cingulate regions.

The left dorsolateral prefrontal cortex is concerned with approach behavior and positive affect. It helps us select positive goals, and organizes and implements behavior to achieve these goals. The right dorsolateral prefrontal cortex organizes withdrawal-related behavior and negative affect, and mediates threat-related vigilance. It plays a role in working memory for object location.

The medial prefrontal cortex integrates cognitive-affective information and helps control the hypothalamic–pituitary–adrenal (HPA) axis during emotional stress (Radley, Arias, & Sawchenko, 2006).

The orbitofrontal cortex is concerned with affective evaluation. It decodes the punishment and reward value of stimuli, and helps inhibit inappropriate behavior. Phineas Gage's profound personality changes were produced by damage to this subdivision.

The anterior cingulate plays an important role in attention and is activated during working memory. It mediates emotional and physical pain, and has cognitive (dorsal anterior cingulate) and affective (ventral anterior cingulate) conflict-monitoring components.

The Stroop test illustrates a cognitive monitoring task, where color and names conflict. Discrepancies between facial and vocal cues illustrate an affective conflict. The anterior cingulate recruits other brain areas to resolve these conflicts.

The parietal lobes are posterior to the frontal lobes and are divided into the primary somatosensory cortex (postcentral gyrus) and secondary somatosensory cortex. Their main function is to process somatosensory information like pain and touch. The right posterior parietal lobe helps guide movements, locate objects in three-dimensional space, and create body boundaries.

The temporal lobes are separated from the rest of the cortical lobes by the Sylvian fissure. The temporal lobes process hearing, smell, and taste information, and help us understand spoken language and recognize visual objects and faces. The amygdala and hippocampus, which lie beneath the temporal cortex, play crucial roles in emotion, declarative, emotional, and working memory, and navigation.

The occipital lobes are posterior to the parietal lobes. They process visual information coming from the eyes in collaboration with the frontal, parietal, and occipital lobes (Wilson, 2003).

The left and right hemispheres communicate using three commissures or axon tracts. The corpus callosum is the largest tract and connects the left and right frontal, parietal, and occipital lobes.

The anterior commissure, shown above the third ventricle at the bottom of the diagram, is considerably smaller than the corpus callosum, and connects the left and right temporal lobes, and the hippocampus and amygdala.

The posterior commissure, located below the corpus callosum, connects the right and left diencephalon and mesencephalon.

Subcortical structures important in neurofeedback include the thalamus, amygdala, hippocampus, and septum.

Caption: This image illustrates the limbic system in the brain from a three-quarter superior view of the cerebrum. Cortical areas are semi-transparent so as to show the limbic system deep within the brain. Structures include the thalamus (purple), hypothalamus (salmon), hippocampus (red), and amygdala (tan).

The thalamus consists of specialized nuclei that relay data to and from the telencephalon (cerebral cortex, basal ganglia, and limbic system). The thalamus preprocesses all sensory data except olfaction before distributing this information to the cortex via thalamocortical afferent fibers. Information must reach the left prefrontal cortex to become conscious. The cortex also sends information to the thalamus to adjust its information processing via corticothalamic fibers. This two-way conversation creates feedback loops that are crucial to the generation of EEG rhythms. The thalamus contributes to slow cortical potentials, 1-4 Hz delta, 8-13 Hz alpha, and 20-50 Hz beta (including 40-Hz activity).

Caption by W. D. Jackson, PhD, and S. D. Stoney, PhD (2006): Thalamocortical cells are subject to excitatory drive from their system afferents, from monosynaptic corticothalamic fibers, and from the brainstem reticular formation (ascending reticular activating system, ARAS). They receive inhibitory drive from local interneurons and neurons in the reticular nucleus of the thalamus (RNT). Note that the RNT neurons are excited by activity in thalamocortical cells and by corticothalamic cells. The connections are precisely organized. For example, each column in a primary cortical area sends corticothalamic fibers back to the same part of its specific thalamic nucleus that sends its thalamocortical fibers to that cortical column. The corticothalamic fibers also synapse on the RNT cells receiving input from that part of the thalamic nucleus. Each cortical receiving area is said to be "reciprocally connected" with its specific thalamic nucleus. Like the thalamocortical cells, RNT cells and cortical neurons also receive excitatory drive from the ARAS.

The amygdala is an important limbic structure located deep within the medial temporal lobes at the end of the hippocampus. The amygdala is comprised of many nuclei, including the lateral nucleus and the central nucleus. The lateral nucleus processes sensory information and distributes it throughout the amygdala. The central nucleus orchestrates the nervous system's response to important stimuli by activating circuits in the brainstem (autonomic arousal) and the basal ganglia and periaqueductal gray (defensive behavior). The amygdala plays a crucial role in learning about the consequences of our actions and in creating declarative memories for events with emotional significance.

Caption: 3-D MRI rendering of a brain with fMRI activation of the amygdala highlighted in red.

The hippocampus is seahorse-shaped limbic structure. The hippocampus is required to form declarative memories and plays an important role in emotion, navigation, and dampening the endocrine stress response. The hippocampus contributes to 4-7 Hz theta activity.

The septum is a limbic structure that contains several nuclei involved in emotion and addiction, and control of aggressive behavior. The septohippocampal system contributes to 4-7 Hz theta activity (Wilson, 2003).

Now that you have completed this module, think about how you might explain the EEG to a client. Which new information about EEG anatomy and physiology did you encounter in this module? If you are a neurotherapist, which placement sites do you use most often? What are the functions of these sites?

Andreassi, J. L. (2000). Psychophysiology: Human behavior and physiological response. Hillsdale, NJ: Lawrence Erlbaum and Associates, Inc.

Babiloni, C., Babiloni, F., Carducci, F., Cincotti, F., Del Percio, C., Hallett, M., Moretti, D. V., Romani, G. L., & Rossini, P. M. High resolution EEG of sensorimotor brain functions: Mapping ERPs or mu ERD? In R. C. Reisin, M. R. Nuwer, M. Hallett, & C. Medina (Eds.). Advances in Clinical Neurophysiology (Supplements to Clinical Neurophysiology Vol. 54). Elsevier Science B. V.

Bear, M. F., Connors, B. W., & Paradiso, M. A. (2007). Neuroscience: Exploring the brain (3rd ed.) . Baltimore: Lippincott Williams & Wilkins.

Bromfield, E. B. (2002). Epileptiform discharges. eMedicine.

Carlson, N. R. (2007). Physiology of behavior (9th ed.). Boston: Allyn and Bacon.

Creuzfeldt, O. D. (1995). Cortex cerebri. Oxford: Oxford University Press.

DeLong, M. R. (1990). Primate models of movement disorders of basal ganglia origin. Trends Neurosci, 13(7), 281-285.

Demos, J. N. (2005). Getting started with neurofeedback. New York: W. W. Norton & Company.

Evans, J. R., & Abarbanel, A. (1999). Introduction to quantitative EEG and neurofeedback. San Diego: Academic Press.

Farwell, L. A., & Donchin, E. (1991). The truth will out: Interrogative polygraphy (“lie detection”) with event-related brain potentials. Psychophysiology, 28, 531–547.

Fox, S. I. (2006). Human physiology (9th ed.). New York: McGraw-Hill.

Garrett, B. (2003). Brain and behavior. New York: Thompson/Wadsworth.

Landisman, C. E., & Connors, B. W. (2005). Long-term modulation of electrical synapses in the mammalian thalamus. Science, 310(5755), 1809-1813.

Meshorer et al. (2002). Alternative splicing and neuritic mRNA translocation under long-term neuronal hypersensitivity. Science, 295, 508-512.

Rosenfeld, J. P., Cantwell, G., Nasman, V. T., Wojdac, V., Ivanov, S., & Mazzeri, L. (1988). A modified, event-related potential-based guilty knowledge test. International Journal of Neuroscience, 24, 157-161.

Hugdahl, K. (1995). Psychophysiology: The mind-body perspective. Cambridge, MA: Harvard University Press.

Julien, R. M. (2005). A primer of drug action (10th ed.). New York: Worth Publishers.

Munro, C. A., et al. (2006). Sex differences in striatal dopamine release in healthy adults. Biological Psychiatry, 59(10), 966-974.

Radley, J. J., Arias, C. M., & Sawchenko, P. E. (2006). Regional differentiation of the medial prefrontal cortex in regulating adaptive responses to acute emotional stress. The Journal of Neuroscience, 26(50), 12967-12976.

Schacter, D.  L. (1977). EEG theta waves and psychological phenomena: A review and analysis. Biological Psychology, 5, 47-82.

M. S. Schwartz, & F. Andrasik (Eds.). (2003). Biofeedback: A practitioner's guide (3rd ed.). New York: The Guilford Press.

Steriade, M. (2005). Cellular substrates of brain rhythms. In E. Niedermeyer and F. Lopes da Silva (Eds.). Electroencephalography: Basic principles, clinical applications, and related fields (5th ed.). Philadelphia: Lippincott Williams & Wilkins.

Sterman, M .B. (2000). EEG markers for attention deficit disorder: Pharmacological and neurofeedback applications. Child Study Journal, 30(1), 1-24.

Stern, R. M., Ray, W. J., & Quigley, K. S. (2001). Psychophysiological recording (2nd ed.). New York: Oxford University Press.

Thompson, M., & Thompson, L. (2003). The biofeedback book: An introduction to basic concepts in applied psychophysiology. Wheat Ridge, CO: Association for Applied Psychophysiology and Biofeedback.

Warren, A. M., & McIlvane, W. J. (1998). Stimulus equivalence and the N400 effect. Poster presented at the 1998 Annual Meeting of the Cognitive Neuroscience Society in San Francisco, CA.

Winn, P. (2001). (Ed.), Dictionary of biological psychology. New York: Routledge.

Wilson, J. (2003). Biological foundations of human behavior. Belmont, CA: Wadsworth/Thompson Learning.

Yang, Y., Ge, W., Chen, Y., Zhang, Z., Shen, W., Wu, C., Poo, M., & Duan, S. (2003). Contribution of astrocytes to hippocampal long-term potentiation through release of D-serine. Proceedings of the National Academy of Sciences of the United States of America, 100(25), 15194-15199.