COMMENTARY

The Neurobiology of ADHD

Robert D. Hunt, MD

Disclosures

September 25, 2006

In This Article

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.[2,16,17,18,19]

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.[7,20,21,22] Damage to the frontal lobes has been associated with impaired executive function, abnormal social cognition, and even impulsive homicide.[23,24,25]

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.[2,26,27,28]

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. 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.

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.

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