Electrodes are able to measure electrical activity in superficial parts of the cortex, with a depth around 5mm, and a surface diameter of around 1-2cm. The electrical activity is measured in pyramidal cells of the cortex, and is related to post-synaptic potentials (PSPs). Action potentials in the axons do not contribute to the ongoing EEG activity as they are too short, go in too many directions relative to the surface of the cortex and are not synchronised. (Note Auditory Evoked Potentials can actually be synchronised in a large number of neurons and can be an exception.) Postsynaptic potentials are changes in the membrane potential of the postsynaptic terminal of a chemical synapse. Postsynaptic potentials are graded potentials, and should not be confused with action potentials although their function is to initiate or inhibit action potentials.
Action potentials are generated by special types of voltage-gated ion channels embedded in a cell’s membrane. These channels are shut when the membrane potential is near the resting potential of the cell, but they rapidly begin to open if the membrane potential increases to a precisely defined threshold value (-55mV). When the channels open (in response to depolarisation), they allow an inward flow of sodium ions, which changes the electrochemical gradient, which in turn produces a further rise in the membrane potential. The process proceeds until all of the available ion channels are open, resulting in a reversal in the membrane potential from -70mV to +30mV. As the sodium channels close, sodium ions can no longer enter the neuron, and then they are actively transported back out of the plasma membrane. Potassium channels are then activated, and there is an outward current of potassium ions, returning the electrochemical gradient to the resting state. A sodium-potassium transporter returns a neuron to its resting voltage following an action potential. The sodium-potassium transporters exchange 2 potassium ions for every 3 sodium ions expelled from a neuron. This allows a neuron to initiate future action potentials. After an action potential has occurred, there is a transient negative shift, called hyperpolarization or the refractory period, due to additional potassium currents. This mechanism prevents an action potential from travelling back the way it just came. When an action potential depolarises an axon’s terminal button, this opens voltage-gated calcium ion channels. Calcium entry into the terminal button causes vesicle movement toward the release zone. There the vesicle fuses with the presynaptic membrane and expels its contents.
EEG reflects voltages generated (mostly) by excitatory postsynaptic potentials from apical dendrites of massively synchronised neocortical pyramidal cells. These cells have dipoles (ie. a pair of equal and oppositely charged or magnetised poles separated by a distance) that can be identified by the electrodes placed over the scalp.
Excitatory Post Synaptic Potential: An excitatory postsynaptic potential (EPSP) is a postsynaptic potential that makes the post synaptic neuron more likely to fire an action potential. This temporary depolarisation of postsynaptic membrane potential, caused by the flow of positively charged ions into the postsynaptic cell, is a result of opening ligand-gated ion channels.
Inhibitory Post Synaptic Potential: These are the opposite of EPSP, and are a decrease in outgoing positive charges, that makes a postsynaptic neuron less likely to generate an action potential.
The axon hillock is the primary site where postsynaptic potentials (EPSPs and IPSPs) are summed to determine whether to initiate an action potential. The phenomenon of long-term potentiation, where synaptic efficiency increases due to activation, has been proposed as an explanation for why neurofeedback training effects persist.
Long-term potentiation is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons.
Long-term depression (LTD) is an activity-dependent reduction in the efficacy of neuronal synapses lasting hours or longer following a long patterned stimulus.
All neurofeedback uses EEG, which is a test used to evaluate the electrical activity in the brain. Brain cells communicate with each other through electrical impulses, and in an EEG electrodes are used to measure these impulses. The EEG used in neurofeedback is examined in slightly different ways to what is termed a ‘clinical EEG’, although they are both measured in the same ways. A Clinical EEG is conducted typically by Neurologists and involves visual examination of multichannel waveforms, in order to detect seizure disorders or encephalopathies. EEG is a good measure as it is low cost, noninvasive, has very high temporal resolution, and provides real-time data of brain fluctuations (thus has many advantages over many other scanning techniques including fMRI, SPECT and PET).
EEG used in neurofeedback include both the visual analysis of the raw EEG (as in clinical EEG) as well as quantitive EEG, or qEEG. QEEG uses Fourier or Wavelet analysis to estimate the frequency spectrum. This breaks down the raw EEG into different bandwidths so that each different type of brain wave or even single Hz can be analysed. These results are then compared to a reference database of people the same age, so that these results can be compared to a ‘typical brain’ free of pathology. The types of comparisons made can be absolute power, relative power, coherence, alpha peak frequency, asymmetry and other comparisons described under the ‘Understanding Brain Waves‘ section. Many studies have found a high level of test-retest reliability for qEEG, which is much strong than that of Clinical EEG.
Clinical applications of qEEG are being used now in medication management, development of neurofeedback protocols, and guiding transcranial magnetic stimulation therapy. QEEG in pharmacology is a very promising area. Most antidepressants and stimulants are prescribed in a complete random way, not based individually on the patient. Through doing a qEEG and examining the patient’s specific profile, more precise medication can be prescribed. Many ‘predictive models’ are being researching looking at which patients will respond best to which medications. For example, one study looked at patients with mood disorders versus patients with attention disorders. They found that irrespective of what their diagnosis was, individuals with slow wave tends to respond better to stimulants, individuals with excessive frontal alpha responded best to antidepressants, and issues with EEG coherence responded best to anticonvulsants or anticyclics. This suggests that qEEG can be better at predicting medication needs that the actual clinical diagnosis (Suffin & Emory, 1995).
QEEG also has exciting prospects for helping guide neurofeedback protocols. When neurofeedback was initially developed, protocols were set purely based on symptoms and arousal levels. Whilst neurofeedback protocols still need to take this into consideration, the use of qEEG can help identify focal areas of interest for training as well as connectivity between brain regions and hemispheres.
Functional magnetic resonance imaging (fMRI), is a technique for measuring brain activity. It works by detecting the changes in blood oxygenation and flow that occur in response to neural activity – when a brain area is more active it consumes more oxygen and to meet this increased demand blood flow increases to the active area. fMRI can be used to produce activation maps showing which parts of the brain are involved in a particular mental process.
Computed tomography (CT) scanning builds up a picture of the brain based on the differential absorption of X-rays. During a CT scan the subject lies on a table that slides in and out of a hollow, cylindrical apparatus. An x-ray source rides on a ring around the inside of the tube, with its beam aimed at the subjects head. After passing through the head, the beam is sampled by one of the many detectors that line the machine’s circumference. Images made using x-rays depend on the absorption of the beam by the tissue it passes through. Bone and hard tissue absorb x-rays well, air and water absorb very little and soft tissue is somewhere in between. Thus, CT scans reveal the gross features of the brain but do not resolve its structure well.
Positron Emission Tomography (PET) uses trace amounts of short-lived radioactive material to map functional processes in the brain. When the material undergoes radioactive decay a positron is emitted, which can be picked up be the detector. Areas of high radioactivity are associated with brain activity.
Electroencephalography (EEG) is the measurement of the electrical activity of the brain by recording from electrodes placed on the scalp. The resulting traces are known as an electroencephalogram (EEG) and represent an electrical signal from a large number of neutrons. EEGs are frequently used in experimentation because the process is non-invasive to the research subject. The EEG is capable of detecting changes in electrical activity in the brain on a millisecond-level. It is one of the few techniques available that has such high temporal resolution.
Magnetoencephalography (MEG) is an imaging technique used to measure the magnetic fields produced by electrical activity in the brain via extremely sensitive devices known as SQUIDs. These measurements are commonly used in both research and clinical settings. There are many uses for the MEG, including assisting surgeons in localising a pathology, assisting researchers in determining the function of various parts of the brain, neurofeedback, and others.
Near infrared spectroscopy (NIRS) is an optical technique for measuring blood oxygenation in the brain. It works by shining light in the near infrared part of the spectrum (700-900nm) through the skull and detecting how much the reemerging light is attenuated. How much the light is attenuated depends on blood oxygenation and thus NIRS can provide an indirect measure of brain activity.
Montage refers to the way the EEG is collected with respect to the placement of the electrodes. It is a method of collecting and representing the EEG amplifier channels. The EEG voltage signal represents a difference between the voltages at two electrodes, and the display of the EEG can be set up in several ways as explained below.
Sequential & Bipolar Montage: Each channel represents the difference between two adjacent electrodes. Eg Fp1-F3 represents the difference in voltage between the Fp1 electrode and the F3 electrode. Both sequential and common reference montages permit excellent detection of electrode artifact (i.e., a potential difference contaminating the EEG due to an extracerebral source).
Referential Montage: A referential montage consists of referential derivations (pairs of electrodes including an active electrode placed in input terminal 1 and reference electrode placed in input terminal 2 of an EEG amplifier). Each channel in this montage represents the difference between a specific electrode and a designated reference electrode. There is no standard position for this reference. Midline positions can be used if you don’t want to amplify the signal in one hemisphere versus the other. A popular type of referential montage is Linked-Ears, which is the average of the electrodes attached to both ears. This is often used as it is the montage used in the popularly used in normative databases such as Neuroguide.
Average Reference Montage: An average reference montage detects the voltage difference between a single electrode placed in input 1 and the average of the remaining 10-20 electrodes placed in input 2. With this montage all the outputs of the amplifiers are summed and averaged, and this average signal is then used as the common reference for each channel.
Laplacian Montage & Weighted Average Reference Montage: A Laplacian montage detects voltage differences between a single electrode and an average of the remaining electrodes weighted in proportion to their distance from the electrode placed in input 1. This utilises the weighted average of electrodes surrounding the electrode of interest for reference. As some electrodes are not surrounded by others, this type of montage will be limited by the edge effects on electrodes on the outside of the 10-20 system. The surrounding electrodes are linearly weighted according to their distance from the main electrode. This is good at localising EEG amplitudes coming from a specific area, as it reduces noise and waveforms from unrelated areas. A Laplacian montage achieves excellent detection of localised neural current sources because it functions as a spatial high pass filter. It can be helpful in medical applications for locating tumours, lesions and epileptiform activity.
Common Electrode Reference Montage: A montage in which the reference electrode is common to multiple derivations is termed a common reference montage. A common reference montage achieves good analysis of asymmetry provided that there is symmetrical placement of the reference electrode(s). Both sequential and common reference montages permit excellent detection of electrode artifact (i.e., a potential difference contaminating the EEG due to an extracerebral source).
Kappa: The kappa rhythm consists of bursts of alpha or theta waves over the temporal region of the scalp when subjects are mentally active.
Lambda: High frequency waves 100-200Hz. Lambda waves are sharply contoured occipital transients evoked by saccadic eye movements scanning a well-illuminated picture or complex design.
Mu: The mu rhythm ranges from 7-11 Hz and is detected over the central or centro-parietal regions of the scalp when a patient is awake. This rhythm is composed of arch-shaped waves that can be blocked or weakened by contralateral movement or the intention to move. Unlike alpha, it is not suppressed by attending to sensory information.
Sleep Spindles: Sleep spindles are synchronous, rhythmic 12-14 Hz waves that usually first appear during stage 2 sleep and reduce our responsiveness to environmental stimuli like noise.
Burst: A burst refers to the abrupt appearance and disappearance of a group of waves that can be discriminated from background activity.
Complex: A complex is a sequence of two or more waves with a characteristic form or recurring with a fairly consistent form that can be distinguished from background activity. Example: a K complex detected during sleep.
Poly Phasic Wave: Polyphasic potentials consist of 250 to 500 ms, medium to high-voltage waves occurring singly or repeating at 2 to 4 Hz. The main body of these waves is usually electropositive. It is often preceded and followed by an alpha wave whose negative-going deflection is greater than usual. Low-amplitude alpha waves may be superimposed upon this 250 to 500 ms potential. These features together create the polyphasic morphology of the phenomenon. Occasionally the accentuated alpha component, together with the after-coming slow wave, can resemble superficially a spike–wave complex, which it is not. Polyphasic potentials may be asymmetrical; if so, they are usually of higher voltage on the right. However, the asymmetry should not persistently exceed 50%.
Spike: Spikes are very fast waves and are called spikes because of their shape on the EEG. Each lasts less than 80 milliseconds (less than 1/12th of a second) and may be followed by slow delta waves. Spikes clearly stand out from other brain activity on the EEG.
Hyper-coupling: An increase in the neuromodulator serotonin produces the hypercoupling that generates global resonances. This leads to sleep spindles and theta and delta activity.
Hypo-coupling: An increase in acetylcholine, dopamine, and norepinephrine produces hypocoupled states which facilitate small regional and local resonance loops. This results in the higher EEG frequencies.
Resonance loops: When the firing of one region results in another region firing, that then loops.
Global resonances: Silberstein (1995) proposed that global resonances are produced by resonance loops between widely separated areas (e.g., frontal-parietal and frontal-occipital regions) and produce EEG activity in the delta-theta range. This resonance can operate spontaneously or can be driven by thalamic pacemakers.
Regional Resonances: Silberstein (1995) proposed that regional resonances are produced by resonance loops between macrocolumns that are several centimeters apart and produce EEG activity in the alpha-beta range. The closer the macrocolumns, the faster the frequencies they generate. This resonance can operate spontaneously or can be driven by thalamic pacemakers.
Local Resonance: Silberstein (1995) proposed that local resonances are produced by resonance loops between adjacent macrocolumns and produce EEG activity in the gamma range (35-45 Hz). The closer the macrocolumns, the faster the frequencies they generate. This resonance can operate spontaneously or can be driven by thalamic pacemakers.
Synchrony indicates that two waveforms are coherent (consistent relationship between their peaks and valleys) and in phase (peak and valleys happening at the same time in both waveforms.)
Nyquist principle: Based on the Nyquist theorem, if you want to perform analog-to-digital conversion on a 25-Hz signal, the sampling rate should be at least 50 Hz. The Nyquist rate is twice the fastest frequency in the signal of interest.
Sampling Rate: In analog-to-digital conversion, the number of digital points per second used to represent a analog signal is referred to as the sampling rate. When a clinician wants to visually inspect a signal that has undergone analog-to-digital conversion, the sampling rate should be at least 6 times the highest frequency of interest or else waveform morphology may be distorted.
Common mode signal: A common mode signal appears at two respective input terminals of a differential amplifier. Example: 50/60Hz artifact is a common mode signal in EEG recording.
Common mode rejection: Common mode rejection is the ratio of the amplification of differential and common mode signals. Common mode rejection = differential amplification/common mode amplification. Example: 25,000/1 = 25,000:1. Common mode rejection is the ability of a differential amplifier to subtract signals common to active and reference electrodes. The difference in signal voltage between these electrodes (which is mainly the biological signal of interest) should be multiplied millions of times more than signals that are common to both electrodes (which are mainly artefact). Fisch and Spehlmann (1999) recommend common mode rejection ratios of at least 10,000 ohms.
Asymmetry: Asymmetry refers to the unequal amplitude and/or form and frequency of EEG activity over corresponding areas on opposites sides of the head.
Reference electrode: A reference electrode is typically connected to input terminal 2 of an EEG amplifier and used to measure the potential variations of an active electrode.
Asynchrony: Asynchrony refers to the non-simultaneous occurrence of EEG activity in regions on the same or opposite side of the head.
Derivation: A derivation refers to both the process of recording from a pair of electrodes in an EEG channel and the resulting EEG record. A derivation is the combination of electrodes used in a single amplifier channel.
Differential amplifier: A differential amplifier subtracts identical input signals. This allows the amplifier to achieve excellent signal-to-noise ratios. A differential amplifier helps reduce 60-Hz artifact by subtracting identical input signals.
Differential signal: A differential signal is the difference between two unlike signals applied to the respective two input terminals of a differential amplifier.
Digital filtering: Filtering adjustments can be performed retrospectively during EEG review when using digital filtering. inite impulse response (FIR), infinite impulse response (IIR), and frequency domain filtering using the fast Fourier transform (FFT) are three approaches to digital filtering.
Low pass filter: A low pass filter reduces the amplitude of higher frequencies while allowing lower frequencies to pass through the amplifier.
High pass filter: A high pass filter reduces the amplitude of lower frequencies while allowing higher frequencies to pass through the amplifier.
Morphology: Morphology refers to the form or shape of an EEG wave.
EEG rhythm: An EEG rhythm consists of waves of approximately constant period. Example: an alpha rhythm.
Epoch: An epoch is a period of time of arbitrary duration in an EEG record. Example: a 10-second epoch.
Notch filter: A notch filter reduces the amplitude of a narrow range of frequencies centered around 50 Hz (in Europe) or 60 Hz (North America).
Evoked potentials: An evoked potential is a wave or complex that is elicited by and time-locked to a stimulus like a light or tone. Evoked potentials index sensory processing speed.
Gain: Gain is the ratio of the output signal voltage to the input signal voltage of an EEG channel.
Aliasing: When an analog-to-digital converter samples an analog signal at a rate less than twice its frequency, the signal will be misrepresented as slower frequency waveforms. This problem is called aliasing.
Resolution: Resolution is the specification that indexes an electroencephalograph’s ability to detect the smallest change in EEG activity. Smaller resolution specifications are better.
Sensitivity: The sensitivity specification measures an electroencephalograph’s ability to detect the smallest signal voltage. Lower sensitivity specifications are better.
Impedance: Opposition to the movement of an AC signal through a circuit is called impedance. We measure impedance to determine the quality of skin-electrode contact.
Comodulation: Comodulation is correlation between the amplitudes of specific frequencies recorded at different sites over time and specific conditions.
Rectifier: A rectifier converts a filtered AC signal into a positive DC signal for integration (calculation of a signal voltage).
Octave: An octave is an interval between two frequencies that represents a 2:1 ratio.
Optical isolator: An optical isolator protects a patient from shock hazard by converting an electrical signal to a beam of light that is projected across a gap and reconverted into an electrical signal.
Bandwidth: The bandwidth is the absolute difference between the high-pass and low-pass frequencies measured in hertz.
Phase: Phase refers to a point on a waveform’s 360 degree cycle at an instant in time. When the peaks and valleys of two waveforms coincide, they are in phase. When they do not coincide, they are out of phase. The degree to which the two waveforms are out of phase is expressed by phase angle which is measured in degrees.
Signal-to-noise ratio: The signal-to-noise ratio is the proportion of signal to artifact amplitudes measured in dB. This value depends on the bandpass selected and should be measured at 60 Hz (since this is frequency of 60-Hz artifact). Example: signal-to-noise ratios should exceed 60 dB (1000:1) to minimize contamination by artifact. This specification should be as high as possible.
Volume conduction: Volume conduction occurs when an EMG signal travels to an EEG electrode and contaminates these recordings. Volume conduction is signal movement across the body through the fluid surrounding cells (interstitial fluid).
Preamplifier: A preamplifier is the first amplification stage in an instrument that requires several stages to increase a low-level signal to voltage levels required for processing.
N100: N100 is a large, negative-going ERP measured by EEG. It peaks in adults between 80 and 120 milliseconds after the onset of a stimulus, and is found mostly over the fronto-central region of the scalp. It is elicited by any unpredictable stimulus in the absence of task demands. It is often referred to with the following P200 evoked potential as the “N100-P200” or “N1-P2” complex. While most research focuses on auditory stimuli, the N100 also occurs for visual and other stimuli.
P300: The P300 wave is an ERP that occurs in the process of decision making. The P300 is thought to reflect processes involved in stimulus evaluation or categorisation. It is usually elicited when low-probability targets are mixed with high-probability non-targets. When recorded by EEG it surfaces as a positive deflection in voltage with a latency (delay between stimulus and response) of roughly 250 to 500 ms. The signal is typically measured most strongly by parietal lobe electrodes. The presence, magnitude, topography and timing of this signal are often used as a measure of cognitive functioning related to the decision making processes.
Contingent Negative Variation (CNV): The contingent negative variation (CNV) is a long-latency electroencephalography (EEG) surface negative potential with cognitive and motor components, observed during response anticipation. CNV is an index of cortical arousal during orienting and attention.
- Brain regions & EEG: When the thalamus reverberates with the cortex, alpha and low beta rhythms are produced. Reverberation between sub-thalamic nuclei and the cortex produces theta rhythms. Cortical-to-cortical reverberations produce faster beta waves. Lateral nuclei of the thalamus inhibit the other thalamic nuclei which project to cortical regions.Inhibition is key in brain self-regulation and meaningful information processing. For example, in order to see SMR in the cortex the laminar thalamic nuclei (using GABA) need to relax their inhibition. Thus, NF is involved in allowing certain inhibitory influences in the thalamus to relax.
- Thalamic Nucleus Reticularis: Allows thalamic pacemakers to adjust their firing frequencies by releasing GABA on relay and inhibitory interneurons. It is part of the ventral thalamus that forms a capsule around the thalamus laterally. Cells have intrinsic pacemaker properties and stimulate thalamocortical cells that produce rhythmic excitation in the cortex. The thalamic reticular nucleus receives input from the cerebral cortex and dorsal thalamic nuclei. Primary thalamic reticular nucleus efferent fibers project to dorsal thalamic nuclei, but never to the cerebral cortex. This is the only thalamic nucleus that does not project to the cerebral cortex, instead it modulates the information from other nuclei in the thalamus. Its function is modulatory on signals going through thalamus (and the reticular nucleus). The thalamic reticular nucleus receives massive projections from the external segment of the Globus Pallidus, thought to play a part in disinhibition of thalamic cells, which is essential for initiation of movement.
- Reticular formation: A set of interconnected nuclei that are located throughout the brainstem. The reticular formation is not anatomically well defined because it includes neurons located in diverse parts of the brain (over 100 small neural networks). The neurons of the reticular formation all play a crucial role in maintaining behavioral arousal and consciousness. The functions of the reticular formation are modulatory and premotor. It is divided into three columns: raphe nuclei (median), gigantocellular reticular nuclei (medial zone), and parvocellular reticular nuclei (lateral zone). The raphe nuclei are the place of synthesis of the neurotransmitter serotonin, which plays an important role in mood regulation. The gigantocellular nuclei are involved in motor coordination. The parvocellular nuclei regulate exhalation. The RF plays a role in sleep and consciousness through projections to the thalamus and cerebral cortex that allow it to exert some control over which sensory signals reach the cerebrum and come to our conscious attention. It plays a central role in states of consciousness like alertness and sleep. Injury to the reticular formation can result in irreversible coma.
- The Reticular Activating System: Is a set of connected nuclei that is responsible for regulating wakefulness and sleep-wake transitions. As its name implies, its most influential component is the reticular formation. The main function of the RAS is to modify thalamic and cortical function such that EEG desynchronization occurs. During vigilance, input from the reticular activating system helps generate the beta rhythm. There are distinct differences in the brain’s electrical activity during periods of wakefulness and sleep: Low voltage fast EEG are associated with wakefulness and REM sleep (which are electrophysiologically identical); high voltage slow waves are found during non-REM sleep.Stimulation of the RAS produces EEG desynchronization by suppressing slow cortical waves (0.3–1 Hz), delta waves (1–4 Hz), and spindle wave oscillations (11–14 Hz) and by promoting gamma band (20 – 40 Hz) oscillations. The physiological change from a state of deep sleep to wakefulness is reversible and mediated by the RAS. During sleep, neurons in the RAS will have a much lower firing rate; conversely, they will have a higher activity level during the waking state. Therefore, low frequency inputs (during sleep) from the RAS to the POA neurons result in an excitatory influence and higher activity levels (awake) will have inhibitory influence. In order that the brain may sleep, there must be a reduction in ascending afferent activity reaching the cortex by suppression of the RAS. The reticular activating system also helps mediate transitions from relaxed wakefulness to periods of high attention. There is increased regional blood flow (presumably indicating an increased measure of neuronal activity) in the midbrain reticular formation (MRF) and thalamic intralaminar nuclei during tasks requiring increased alertness and attention.
- GABA: GABA is the main inhibitory neurotransmitter in the CNS.
- Serotonin: The neurons of the raphe nuclei are the principal source of serotonin release in the brain. There are nine raphe nuclei which contain the majority of serotonin-containing neurons all of which are located along the midline of the brainstem, and centered on the reticular formation. Axons from the neurons of the raphe nuclei form a neurotransmitter system reaching almost every part of the central nervous system. Axons of neurons in the lower raphe nuclei terminate in the cerebellum and spinal cord, while the axons of the higher nuclei spread out in the entire brain.
- Dopamine: The brain includes several distinct dopamine pathways, one of which plays a major role in reward-motivated behaviour. Most types of reward increase the level of dopamine in the brain, and many addictive drugs increase dopamine neuronal activity. Other brain dopamine pathways are involved in motor control and in controlling the release of various hormones. These pathways and cell groups form a dopamine system which is neuromodulatory.
- Acetylcholine: Acetylcholine functions as a neuromodulator—a chemical that alters the way other brain structures process information rather than a chemical used to transmit information from point to point. The brain contains a number of cholinergic areas, each with distinct functions. They play an important role in arousal, attention, and motivation.
- Norepinephrine: Norepinephrine is produced in closely packed brain cell neurons or nuclei that are small yet exert powerful effects on other brain areas. The most important of these nuclei is the locus coeruleus, located in the pons. The general function of norepinephrine is to mobilise the brain and body for action.