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The Experience of Attention

Attention is a lot like love. Everyone knows what it is and when it's present, but the multiple components of attention defy easy definition.
Attention is the thread that holds together the fabric of our consciousness. For all we know about brain function, the greatest mystery is
consciousness itself. How are we aware of what we perceive? How do we know what we know? Attention encompasses the process that
allows us to focus on what is important and to filter out what is trivial. Much of this process occurs preconsciously, without effort or
awareness. Voluntary attention links the thoughts and emotions we consciously choose to focus on. Because it operates at such a basic
level, the process that regulates attention must be very connected to a fundamental sense of self. How we focus our thoughts and feelings is
a major expression of self. We ponder what is the "I" that directs our attention.

We know that neurotransmitters such as dopamine and norepinephrine are critical to the language of attention, providing the means of the
communication of information across synapses vital to alertness and focus, prerequisites to content. But where, and on what brain systems,
do these neurotransmitters operate?

While the nature of attention has been widely discussed, there is a need for an integrative analyses, which is offered here.[1-3]

Components of Attention

To understand attention, one must first deconstruct its components. A process as complex as attention is not one process but many
processes acting in concert. Attention must encompass at least these components:

Arousal and alertness -- the prerequisites to attention

External or receptive attention: sensory processing and interpretation -- as with reading

Internal or reflective attention which includes thinking about ideas, concepts, and organization of projects or tasks

Processing attention or selective attention. This includes:

A. Focus -- tuning in to an object or topic

B. Filtering -- signal:noise gradient -- enhancement or activation of relevant stimuli

C. Inhibition of sensation (sensory inhibition) -- selective sensory input

External or expressive attention -- encompasses what we choose to communicate or suppress, which also evokes components
of focusing, filtering, and inhibition.

Working memory -- accessing the retrieval and storage of working memory, ie, the flow of information, the content of active thought

The Process of Attention

Consider the process of landing an aircraft, which has been studied extensively in terms of altitude variables, flight safety issues,[4] and the
layout of instruments on the flight panel.[5] However, it is an interesting example in terms of attention because throughout the process of
flying, a pilot's attention is alternatively proactive and responsive. The pilot has to maintain an automatic scan between the instruments that
identify his current position in terms of pitch (climbing or descending), roll (turning), and horizontal/lateral (direction) axes. He must also track
the gradual descent of altitude. In addition, air traffic control may alter his flight path to accommodate other aircraft in the landing pattern
and in response to runway availability and wind direction on the ground. All of these accommodations are also made in a context of weather
conditions, in order, for example, to avoid thunderstorms and minimize turbulence. But the pilot must also monitor the plane's internal
conditions -- the power settings, manifold pressure, and fuel levels. In flight, the pilot must continuously shift attention to monitor the location
and functioning of the plane using the internal flight instruments, and modify it if directions from air traffic control, ambient weather, or other
nearby aircraft warrant it. Mastering an automatic scan between the instruments that identify the plane's direction, pitch (up for climb; down for
descent), tilt (wings level or rotated), and air speed is an essential component of flight training. Finally, as the runway comes into sight, the
pilot shifts his attention towards monitoring the craft visually, in relation to the touchdown markings on the runway.

As a pilot charts the course, he varies altitude, position and speed depending on location and direction from air traffic control. His principle
source of information, the object of his attention, shifts from visually monitoring the instruments to auditory interactions with air traffic control.

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His cognitive set shifts in response to the varying priorities of changes in altitude, fuel consumption, direction, weather, and wind conditions.
A sudden jolt or small shift in ongoing sounds may immediately demand a change of attention, either to weather conditions or engine
performance. The priority of his attention shifts from internal instruments to external environment, from the cockpit to the runway, from
auditory to visual, as he maintains and sustains a 3-dimensional picture of location and situation. Often a pilot has to override his strong tactile
(proprioceptive) sensation, such as when the instruments tell him that he is descending to the left and his body feels as if he is climbing to
the right. A major risk for an amateur pilot would be to become fixated or stuck on one instrument to the neglect of essential information from
other sources. When conditions change, attention must follow.

The interwoven processes of attention can be subgrouped as: (1) the prerequisites for attention, which includes adequate arousal and
alertness and the organization of goal-directed purpose or interest; (2) the content of attention, which extends to sensory processing,
thoughts or ideas, and memory accessing; (3)the process of attention, which involves both receptive attention and expressive
attention. In both directions, attention primarily constitutes enhancing the signal:noise gradient by magnifying sensory information,
emotions, or thoughts that are relevant while concurrently inhibiting stimuli that distract or interfere; (4) brain structures involved in
attention, including the parts of the brain specifically involved in ADHD, like the striatum and the prefrontal cortex; (5) the modulation of
attention, which includes processes that amplify or reduce attention, such as mood.

This process of deconstructing attention always runs the risk of drawing artificial boundaries between the specific cognitive processes
essential to sensory or information processing and those components that specifically embody the mechanism of selection and continuity
that comprise attention.[5-8]

Prerequisites of Attention

Arousal and alertness are essential to maintaining vigilance, to scanning the environment both inside the cockpit and outside the aircraft.
Sensory processing of both visual and verbal information, as well as their correct interpretation, is essential in order for the pilot to
determine his position, altitude, pitch, and direction. The pilot continually shifts his attention by changing focus from flight to engine
instruments, from visual to auditory information. Even though he hears conversations with all aircraft on his frequency via air traffic control, he
is constantly filtering auditory signals in order to respond only to those with his call letters, 864JWN (Juliet, Whisky, November). One of the
tasks of a pilot is to be highly selective in the information he transmits to flight control, thus exemplifying selective expression. He must
inhibit his response to both extraneous instructions directed to other aircraft and unessential information that would clutter the airways and
consume valuable air traffic control time. Much of initial flight training addresses communication that is highly effective and teaching a
would-be pilot to provide only ended responses to direction and inhibit unnecessary chatter. All of these processes consume working
memory, which is capacity-limited by how much information one can hold in memory at one moment (such as the length of digit span forward
or backwards).

Effective attention requires sufficient alertness to mobilize filtering and sustain connection and interpretation of information. The ability to pay
attention depends on maintaining adequate arousal to support adequate alertness in order to process information effectively. It is hard to
sustain attention when we are fatigued or depressed. Attention involves emotion as well as cognition and reflects the sensorial strength of
the external stimulus and the salience or degree of interest a person has.

At many levels, attention is like a dance requiring the coordination of cortical and subcortical functioning.[9] Spatial attention, for example,
involves subcortical modulation of sensory experience.[10]

The neurobiological substrate of arousal encompasses several brain systems. The most critical structures for maintaining alertness
include the reticular activating system. This system, beginning in the brain stem, is primarily activated by norepinephrine (NE) arousing
from the locus coeruleus (LC) located in the area of the pons. The LC sends diffuse projections throughout the cortex and cerebellum,
extending to the limbic system and down the spinal cord. These projections regulate both tonic (baseline) level of arousal and phasic
(episodic) or event-activated arousal.[11-13] Tonic arousal helps us to stay awake while driving at night, even when we are tired. Phasic
arousal is activated when the traffic suddenly stops on the freeway, and when, facilitated by a sudden NE surge, are able to quickly slam on
the brakes and swerve.

Orientation. This NE surge, or burst of energy, enables us to orient to a situation, respond immediately, ie, to come "alive" and react quickly.
The diffuse localization of NE neurons facilitates this broad impact on behavior and thought essential for survival in the jungle, or in an
environment filled with surprise and danger. The spatial localization of events essential to orientation involves the parietal lobe.

Sensory Attention: Working Memory Arousal, Filtering, Inhibition

Sensory processing. The ability to selectively process incoming information requires both specific and more generalized
neurotransmission. The generalized components of sensation require noradrenergic activation of attention. Once we are engaged, the
process of focusing requires attachment and filtering: the subjective amplification of stimuli that are important and the inhibition or
downregulation of stimuli that are incidental. Attention is essential to processing language involved in the visual attention applied to reading; it

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is also essential in auditory attention when we are engaged in conversation or are listening to a symphony.

The extent to which we must apply effortful attention depends in part on the characteristics of the stimulus -- whether the stimulus or
object of our attention is interesting, colorful, and intrinsically engages our curiosity. The cognitive effort for discrimination partially depends
on how distinct the relevant stimuli are from background noise. It is much easier to process information that is moving, changing, and
multisensory, such as watching TV or a movie. The attentional burden greatly increases if the stimulus is static, black on white, and does not
come to life until we pay attention to it. No wonder many more people would rather see the movie than read the book! In an age of
multisensory stimulation and omnipresent entertainment, shifting attention internally towards quiet contemplation or values formation or
personal goals and strategies, or even internal problem solving, becomes more difficult.[6]

Inhibition. Our ability to selectively ignore repetitive or nonessential stimuli begins at the sensory, subcortical, and preconscious levels. Our
capacity to listen carefully and selectively, to focus on a quiet but informative conversation in a noisy room, for example, requires
noradrenergically mediated auditory discrimination.

Our internal emotional state colors the way we process information.[14] When we are depressed, our sensory sensitivity may be dampened
and we may more often notice the objects that fit our mood. Similarly, anxiety can also blunt attention by preempting our focus by our internal
anxiety, leading to distraction.[15]

Interest. Our ability to pay attention also depends on personal characteristics, such as our degree of alertness, our subjective interest in the
subject, and the importance or motivation it has for us at the moment. We often pay attention to stimuli that are not intrinsically engaging, but
which reflect our sense of purpose, priority, and importance. For example, we pay attention to taxes, even if we do not find the process or
stimuli intrinsically interesting. A premed student may focus intensely on learning organic chemistry even if he or she is bored by the subject.

The Processes of Attention

This process of sensory-emotional filtering occurs at several levels: peripherally at the sensory level, and centrally at the more
interpretive level. Objects in the visual sensory environment automatically potentiate neuronal activation as implicit processing, identifiable on
functional magnetic resonance imaging (fMRI).[14] The processes of focusing, interpreting, inhibiting, linking, connecting, and then storing
information are all connected by the thread of attention and involve many cognitive and affective structures in the brain. For sensory stimuli,
processing usually begins with the eyes and ears. The identification of form and shape involves the associative cortices; the localization of
stimuli occurs in the parietal lobes; and the interpretation of their significance and relevance involves the frontal cortex. The independent
auditory and visual stimuli from a single source is integrated in the dorsal temporal areas for auditory input and in the ventral temporal regions
for visual stimulation. These messages are linked in the association cortices that have projections to the limbic areas for affective relevance
and to the prefrontal cortex for cognitive assimilation. Stimulus sequencing in movement involves the cerebellum and the caudate lobes.[2,
16-19]

Inhibitory aspects of attention. At a sensory level, the ability to inhibit distractions when we are paying attention to something else is
partially cortically mediated at the frontal cortex, layers 3-4, by alpha-2a-receptors. At a behavioral level, cortical inhibition enables control of
impulsive action. The ability to not speak or act impulsively is a significant component of maturation, and requires learning, often from
negative experiences. While much of our learning occurs at a cortical level, considerable behavioral inhibition involves the inferior prefrontal
cortex (PFC). Medications such as guanfacine and clonidine act on these presynaptic receptors to downregulate a response to distractions.
[7,20-22]
Damage to the frontal lobes has been associated with impaired executive function, abnormal social cognition, and even impulsive
homicide.[23-25]

Reflective attention. We not only pay attention to the outside world, we focus considerable awareness on internal thoughts, feelings, and
memories. Memory itself may have an affective filter: When we are happy and optimistic, we may recall and anticipate more positive
experiences; when we feel depressed or anxious we may notice and recall more disheartening experiences.[2,26-28]

Executive function and attention. The ability to make effective decisions requires integrative and sustained attention. The ability to search
memory, to link current sensation to immediate context and connect this experience to past memories, is the quintessential attentional
task.[3] Planning and working memory are essential components of executive function.[1,2] The capacity to do what we intend requires
sustain attention, even in an environment of distractions and through phases of weakening interest or mounting fatigue.[29]

The cognitive aspects of executive function are primarily located in the anterior frontal cortex, whereas spatial organization occurs more
dorsally; verbal memory and organization are localized more internally. Anticipatory, or expectant waiting, aspects of executive function are
managed in the cingulate gyrus. The ability to interpret visual experience -- an important component in executive learning -- is processed in
the posterior visual cortex. Visual orientation is localized in the dorsal visual areas; visual features are analyzed more inferiorly. As evident
on fMRI, executive function is highly vulnerable to damage from traumatic brain injury.[30] Even unilateral frontal lobectomy can disturb the
ability to apply strategy and intention to behavior.[31]

Language. The greatest evolutionary progress that differentiates humans from other primates is sophistication of language and reasoning.

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Though these are clearly distinct processes, they are highly interconnected. Cortical and subcortical structures are involved in
language [32,33] and reading.[34] Social cognition, our understanding of social process, includes integration of sensory visual and auditory
processes,[35] with an understanding of intention linked to motivation and empathy processed in the frontal lobes.[23,24] Written language can
be affected by selective epilepsy as identified by neuropsychological and neuroimaging techniques.[36]

Brain structures in attention. Where does attention begin in the brain? The answer depends on where the object of attention originates --
in the external environment or within the mind or the body. We frequently pay greatest attention to our own thoughts and emotions, which
arise internally without an immediate external referent. These promptings may begin in the frontal lobes or in affective regions of the temporal
lobes or limbic system. Memories may have their origins in the temporal lobes; feelings may spring from limbic centers.

Much of the generation of attention begins subcortically, in the basal ganglia, which receive projections related to internal states and also
process steady-state repetitive stimuli, including speech.[37] The basal ganglia also contribute to motivation and, when excessively aroused,
to anxiety.[38] In many ways, the basal ganglia, acting in concert with the anterior cingulate, function as the executive assistant to the
frontal lobes. These structures process considerable automatic information whose relevance and disposition do not require conscious
thought or effort, thereby reserving the prefrontal cortex for more complex and significant tasks. Patients with bilateral damage to the
anterior caudate lobe have difficulty with anticipatory and sequential aspects of attention. Within the frontal lobes, those aspects of
working memory (or conscious thought) that involve spatial localization are analyzed more anterior-dorsally, whereas word processing occurs
more inferiorly in the dominant lateral cortex.[3] The frontal lobes, in association with the basal ganglia and anterior cingulate, are involved in
shifting set or anticipation of what is next.[19] Within the visual cortex, discrimination of form and feature occur more inferiorly, whereas visual
orientation is localized more dorsally. Damage to the right orbitofrontal region and excessive activity within the anterior cingulate gyrus have
been associated with symptoms of OCD.[39]

As shown in single photon emission computed tomography (SPECT) brain imaging scans, when a person marshals enough attention for a
task requiring sustained vigilance, there is an increase in blood flow in the frontal lobes area.[40] However, patients with attention-deficit
disorder (ADD) show a relative decrease in blood flow in the inferior orbital prefrontal cortex when they attempt to perform complex
attentional tasks. But when they are treated with psychostimulant medications, such as amphetamines, the sufficient blood flow needed to
provide the essential oxygen and glucose necessary to enhance catecholamines and facilitate inhibition does occur.

Interest. The ability to maintain interest and to attach and sustain attention is predominately dopaminergically mediated through actions in
the nucleus accumbens, the center of pleasure or reinforcement. Dopamine in the mesolimbic system is critical to the attachment of
attention: to fixing, filtering, and sustaining interest, pleasure, and attention.

Interpretation. The ability to interpret the meaning and significance of an event depends on activation of anterior frontal cortical function.[41]
Our ability to read social cues and develop interpersonal strategies also involves the frontal lobes.[28,31] Much of what we pay attention to is
internally initiated, such as reflection or problem-solving about something not in our immediate sensory environment. This includes the ability
to interpret meaning in its conceptual context, essential to the recognition of sarcasm and humor. The process of interpretation and
reasoning is more noradrenergically mediated, and has links to memory as well as to visual and auditory sensory systems. Medications
such as atomoxetine facilitate this higher cortical processing.

Memory is involved in many aspects of consciousness. Short-term working memory includes the active processing of current awareness
in relation to prior experience stored in long-term memory. Most aspects of short-term working memory engage the anterior cingulate gyrus,
whose regions of activity link to the frontal lobe as shown in the Figure.

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Figure. Linked to the frontal lobe, the anterior cingulate gyrus is engaged in the process of short-term working memory.

Long-term memory is stored in the temporal lobes. Speech and language involve many of these structures, with expressive language
being located more anteriorly and receptive language more posteriorly, predominantly on the left side. The temporal lobe and Broca's area
have active roles in language, with the dominate lobe (usually left side) being more engaged in word-finding; the nondominant side
contributes more to prosody, the rhythmic and affective aspects of speech.

Brain Structure and Function

No designation of which brain areas perform which cognitive or affective function can be accurate or complete. Most complex tasks involve
multiple functional circuits that link many structures. The cerebellum is predominantly engaged in the coordination of movement and
timing, and serves as a linking and integrative system for many cortically initiated activities. This integration of timing is not limited to
movement; it can extend to the cognitive and affective domain. However, selective damage to the cerebellum can produce cognitive and
affective symptoms.[42]

The thalamus, a large, deep structure located in the middle of the brain, regulates many components of overall arousal and provides a
reciprocal relay between multiple subcortical structures and the cortex. Given its central location, the thalamus has tremendous impact on a
wide spectrum of functions, including language, mood, and depression.[43,44]

The basal ganglia, caudate, and putamen, critical to motivation and the regulation of affective intensity, provide a relay for regulation of
movement. Bilateral damage to the caudate nucleus can produce symptoms of dyscontrol and impulsiveness that mimic those of a frontal
lobe syndrome[38] and affect the cognitive and motor aspects of speech.[37,45] The basal ganglia act in concert with the frontal lobes in
interpreting perceptual experience[6] and are associated with ritualistic social behavior in animals and in man.[5]

The temporal lobes (TL) on the dominant side contribute to language through word finding and sequencing. The nondominant TL lobes are
involved with syntactic aspects of language -- rhythm and expression. The TLs are essential to visual recognition memory[46] and effective
response to visual and olfactory stimuli.[28] At the tip of the TLs, bilaterally, are the amygdala, the early warning system of the brain that
responds to change and assesses danger vs opportunity in the environment. In EEG studies, the amygdala is activated when a subject is
shown threatening faces but not benign images.[47]

The anterior cingulate participates in many aspects of executive function and working memory, and retains information in a state of
expectant alertness, such as when you are looking for a particular street sign in an unfamiliar city. It also plays an important role in sustaining
vs changing expectations and shifting set, the working instructions of what to do or anticipate next.

The prefrontal cortex integrates and manages the purposeful functioning of most other brain structures, receiving input and providing
reciprocal regulatory control of many brain areas. While other brain regions perform the primary processing of stimuli and information, the
frontal lobes interpret and provide meaning to this experience. This is the main site of voluntary, or conscious, thought and planning. The
prefrontal cortex is the chief executive center of the brain through which conscious perception of our environment occurs, and where
decisions are made, not only about how to react but how to affect the world and our lives. The frontal lobes are proactive, not just reactive.
They are receptive and contemplative, not just responsive or active. This is where we have our primary experience of self. The broad agenda

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of the prefrontal cortex is to facilitate living a purposeful life. Relevant integration is required to connect long-term goals with the specific
actions required at the moment, and to issue the commands that turn these plans into purposeful behaviors.

Although we describe these cognitive processes sequentially, they occur virtually simultaneously. As new stimuli arise, either of sensory or
internal origin, process of selection, interpretation, memory, and purposeful reasoning are activated. Given the limits of sequential language,
we describe these activities as occurring in specific brain areas, but in reality they occur through neural networks involving simultaneous
activation of multiple pathways and through neurotransmitters functioning in concert.

Neurochemistry and the language of attention. Three neurochemical dopamine pathways convey messages for functioning that are
attentionally linked. Path 1, the energy pathway, connects the substantia nigra to the motor cortex via the basal ganglia and enhances
physical energy. Path 2, the desire pathway, connects the caudate lobe to the premotor cortex via the orbital prefrontal cortex. Path 3, the
pleasure pathway, connects the ventral tegmental nucleus (the origin of dopamine [DA] cell bodies) to the olfactory bulb and frontal lobes
via the basal ganglia so that mental energy, drive, and a sense of pleasure are transmitted. DA facilitates desire, pleasure, and interest which
contribute to sustained and selective attention. NE contributes to attention through the regulation of alertness and arousal and to cognition
and executive function, which extend attention into thought.

Disruption of attention. Attention is modified and influenced by noncognitive factors that reflect other personality or psychiatric
considerations that can alter the depth and breath of attention. For example, attention may be scattered by ADD, decreased by fatigue, or
accelerated and disorganized during mania. Obsessive-compulsive disorder (OCD) can lead to the overfocusing of attention and lack of
cognitive flexibility. During depressive episodes, the rate of information processing and the depth of attention is diminished. Anxiety can
interrupt sustained attention and decrease the allocation of attention to problem-solving. Effective attention requires an optimal balance of
alertness, mood, and cognitive flexibility.

Attention is not only mediated by catecholamine neurotransmitters[48] but by hormones arising from the hypothalamic-pituitary-adrenal axis.
Hormones as well as neurotransmitters affect alertness and have a direct effect on DA, as is evident by changes in levels of the plasma
metabolite HVA.[49] Hormonal activity occurs over a longer time frame, affecting the general neurobiological environment or substrate,
whereas neurotransmitter activity is virtually instantaneous and commands momentary, specific events.

Organization and executive function. Attention is also required for the reorganization of information necessary for decision-making,
priority setting, and optimal execution of decisions and strategies. The information studied the night before a test needs to be reorganized
during the exam or for application to a new situation. The pilot who has practiced instrument landings "under the hood" in fair weather must be
able to apply these skills if he flies through a blinding snow storm.

Many neurochemical processes and neurobiological systems are involved in reorganizing information from memory and in applying this
known information to novel problem-solving. For example, during the diagnostic process, physicians must reorganize information they
learned during their first 2 years of medical school to guide them to an understanding of the underlying etiology or cause of a patient's
problem. In the first years of medical school, a student primarily learns about organ function and what symptoms can occur when something
goes wrong. During the clinical years, this information needs to be reorganized, beginning with the symptoms which must be inferred to
determine which organs are involved in he particular symptoms. Information stored in long-term memory must be accessed and reorganized
using a different -- actually reversed -- system. Because similar symptoms can be caused by very different underlying medical problems
(consider fever or headache), the organizational and hierarchal structure must be reconstructed, not simply reversed. The relationship
between afferent input and cortical organization has been studied with magnetic stimulation.[35] The ability to reorganize and resynthesize
information is a frontal cortical process that depends heavily on noradrenergic functioning in the frontal cortex.[26] The capacity to attach
attention, filter information, and sustain focus is highly dopaminergic.[50] Serotonin interacts with and modulates the response of striatal D2
dopamine receptors and cross-modulates the sensitivity of NE receptors.[51] Collectively, these and other neurotransmitters facilitate the
sustained link of sensation to memory and the capacity for working memory and analytic thinking.

Differentiating medications for attention. Several medications have distinct and relatively discrete effects on the spectrum of attentional
processes.[52] Modafinil (Provigil) primarily increases wakefulness, a component of this arousal process, which appears to be mediated
by activation of the histamine receptors. Amphetamines also increase alertness and active attachment of attention, which are prerequisites
to problem-solving and reasoning. Their major sites of action are the D2 receptors located in the striatum, which has projections to the
mesocortical DA regions. While the primary effect of methylphenidate is to increase DA concentration within the synapse by blocking
presynaptic reuptake, amphetamines have the secondary effect of increasing NE production and release.[13] Amphetamines increase
alertness and enhance signal:noise differentiation, which is essential to sensory filtering and cognitive-behavioral organization. In contrast,
atomoxetine (Strattera) predominately acts to block frontal-cortical NE reuptake with limited secondary effects on frontal DA. The
predominant NE effect is on executive functioning, ie, postattentional information processing. There is some preliminary evidence, in part
derived from our studies (R. Hunt, unpublished data) that atomoxetine may play a beneficial role in the treatment of some forms of dyslexia,
but that it has little direct effect on the process of attaching attention in ADD patients. The memory components of this process may be
enhanced by medications traditionally considered to be Alzheimer's medications, including memantine HCl (Namenda).

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Authors and Disclosures

Robert D. Hunt, MD, Center for Attention and Brain Function, Nashville, Tennessee

Disclosure: Robert D. Hunt, MD, has disclosed that he has received grants for clinical research from Lilly, and has served as an advisor or
consultant to Shire, Cephalon, Novartis, and Astra-Zeneca.

Medscape Psychiatry & Mental Health. 2006;11(2) © 2006 Medscape

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