OVERVIEW

Neuropsychological assessment is a formalized method of observing patients’ behaviors. It distinguishes itself from other methods of inquiry regarding behavior in its goals and its methodologies. The core method of observation is the administration of standardized tests. These tests assess a patient’s level of function within different cognitive domains, and in particular, they provide information regarding which aspects of behavior are impaired and which are spared. Based on data obtained from these tests, the evaluation provides clinically relevant information regarding etiologies underlying behavioral impairment, as well as information that can inform patient care and treatment. In this chapter, we present an overview of the practice of clinical neuropsychology, including its definition, goals, types of patients referred for assessments, domains of cognitive function assessed, and the types of measures used to assess cognitive function.

The science of neuropsychology is dedicated to the study of brain-behavior relationships. Our understanding of how behavior is organized in the brain has been informed by observations of patients with focal brain lesions,^1,² by studies of cognitive impairment associated with different underlying disease processes,^3,⁴ and, most recently, by neuroimaging techniques, including magnetic resonance imaging (MRI), functional MRI (fMRI), positron emission tomography (PET), and magnetoencephalography.^5,⁶ Data from these different sources inform our understanding of the neurological underpinnings of behavior and are used by clinical neuropsychologists in linking patients’ neuropsychological test performance with underlying brain dysfunction.

In assessing behavior, the clinical neuropsychologist focuses primarily on domains of cognitive function (including attention, executive function, language, visual perception, and memory). The nature of a patient’s cognitive impairment, as well as the pattern of impaired and spared behaviors, is helpful in distinguishing different underlying neurological conditions, in differentiating neurological from psychiatric conditions, and in discriminating normal from abnormal performance.⁷ Patients’ cognitive behaviors are specifically measured or quantified, allowing the neuropsychologist to determine whether a patient is performing “normally” within a particular cognitive domain and, if not, to determine the extent of impairment. The neuropsychologist uses the data obtained to address practical questions regarding patient care, including information regarding a patient’s prognosis and a patient’s ability to manage various aspects of his or her life (e.g., to live independently, to return to work, to comprehend and to follow medical instructions, and to comprehend legal documents), and to recommend possible treatments, interventions, or strategies from which a patient might benefit. Finally, as the information provided is quantified, repeat neuropsychological assessments are used to track the course of a patient’s disease.

Referrals for neuropsychological evaluation typically originate from a patient’s treating physician (most often a neurologist, neurosurgeon, psychiatrist, or internist), but patients or their family members can also initiate a referral. Referred patients may have known neurological disease or damage, or may display or complain of cognitive dysfunction caused by an unknown or unclear etiology. Patients assessed include those with acquired impairments and developmental impairments. Developmental impairments (e.g., learning disabilities, attention-deficit/hyperactivity disorder [ADHD], pervasive developmental disorder [PDD]) arise when the brain fails to develop normally, with the cause often unknown. For children with developmental impairments, the neuropsychological evaluation can play an important role in determining the diagnosis. For adults with developmental impairments, a neuropsychological assessment more commonly focuses on the impact of the impairment on the adult’s ability to function within different settings (e.g., higher education or work settings), and whether accommodations might help address the areas of difficulty. Acquired impairments (e.g., stroke, head injury, or dementing illnesses) result from neurological disease or damage that often occurs after a period of normal development. The manifestation of acquired impairments in childhood often differs from that in adulthood, with localized cerebral pathologies more common in adults and generalized insults to the central nervous system (CNS) more common in childhood.⁸ Study findings differ regarding whether the recovery profiles of children are better than those of adults, due to greater brain plasticity,^9,¹⁰ or whether the developing brains of children are more vulnerable to the effects of neurological insults than are the mature brains of adults.¹¹

Given that the goal of a neuropsychological evaluation is to determine whether behavioral function has been altered (and if so, to what extent), a critical issue that arises when characterizing the cognitive status of a patient with an acquired impairment is the determination of his or her premorbid level of function. Because “baseline” neuropsychological data are rarely available, the neuropsychologist relies on indirect methods to estimate a patient’s premorbid level of intellectual function. These include consideration of historical and observational data (such as level of education and occupational history, previous relevant medical history, and examination of a patient’s performance on specific cognitive tests). Specifically, certain classes of learned information (e.g., knowledge of word meanings, factual information, and word recognition) are highly correlated with premorbid intelligence and are generally resistant to the effects of neurological disease.^7,¹² The neuropsychologist also considers the patient’s pattern of performance across an array of cognitive measures. For nonimpaired individuals, performance is generally consistent across cognitive domains, whereas for impaired individuals, wider scatter across tests is more common, with higher scores typically reflective of premorbid function and lower scores generally indicating impairment.⁷

While an estimation of the premorbid level of function is necessary for the interpretation of normally distributed behaviors (Figure 8-1), for behaviors that are more even across individuals (i.e., “species-wide” behaviors), such methods are unnecessary (with any behavioral dysfunction indicative of impairment) (Figure 8-2).⁷

Figure 8-1 A normative curve, which displays the distribution of scores around the mean. The figure shows the relationships between different normative scores, with each having a different mean and standard deviation.

Figure 8-2 Responses to the Trail Making Test. Part A (Sample) and copy of an elephant provided by a patient with a right parieto-occipital stroke. The patient’s left-sided neglect does not require reference to normative data, because the ability to attend to both sides of spaces is a species-wide behavior.

(From Reitan RM, Wolfson D: The Halstead-Reitan Neuropsychological Test Battery, Tucson, AZ, 1985, Neuropsychology Press.)

Within the class of normally distributed behaviors, individuals display a range of abilities. For these behaviors, the neuropsychologist compares a patient’s performance (i.e., raw score) to that of a normative sample. Tests that are most reliable are those for which there is a large normative sample against which a patient’s performance can be compared, and for which the normative sample is stratified according to age, level of education, and sometimes gender. In interpreting a patient’s test performance, the neuropsychologist converts a patient’s raw scores to “standard scores,” expressed according to the normative mean and standard deviation (SD) (see Figure 8-1). Scores vary in the types of standard scores expressed (e.g., Standard Scores, T-scores, Scaled Scores, or Z-scores). Scores that fall within the mean of the normative sample are considered to fall within the “average” range, and those that fall significantly above or below the mean are considered areas of strength or weakness, respectively. Scores that fall 2 SD or more below the mean are generally considered “impaired” (see Figure 8-1). In interpreting test scores, the neuropsychologist considers how the patient’s performance compares not only to the mean but also to the patient’s own profile of scores. A patient who scores well above the mean on most tests but below the mean on selective measures may be considered to exhibit “impaired” performance (relative to the patient’s premorbid level of function), even though the level of performance may not fall strictly in the “impaired” range on any measure. Neuropsychological tests are also characterized by standardized administration, with test questions presented to all patients in the same way, and with patients’ responses to stimuli scored in a standardized manner. Given that the neuropsychologist relies on normative data to interpret patients’ performances, this interpretation is meaningful only if standardized test administration and scoring procedures are adhered to.

While patients’ performances (i.e., “scores”) on a set of neuropsychological tests are the core set of data obtained from a neuropsychological evaluation, their behavior on tests can only be understood within the context of their developmental and medical history, as well as their current cognitive complaints. In addition, test data also need to be interpreted within the context of clinical (i.e., qualitative) observations regarding the patient’s mood, motivation to perform, attention-to-task, and comprehension of task instructions. These observations are of particular importance when assessing the validity of test performance (especially when assessing questions of possible malingering). Moreover, in interpreting test behavior, a neuropsychologist relies not only on the specific score that a patient obtains on a test, but also on the patient’s response style (e.g., whether it is very slow, impulsive, concrete, or perseverative in nature). This careful analysis of patient behavior can provide the most meaningful information regarding a patient’s level of competence, as well as how different performance variables affect a patient’s ability to express that competence.

In the following sections, we describe the domains that are typically assessed within a neuropsychological evaluation. It should be noted that these descriptions are by no means exhaustive, but instead are presented as an overview of the types of questions and methodologies that are employed in a neuropsychological evaluation in addressing questions regarding diagnosis and patient care.

DIMENSIONS OF BEHAVIOR ASSESSED

Intellectual Function

To interpret behavior within specific cognitive domains, a neuropsychological evaluation nearly always includes a measure of intellectual function. Intelligence can be estimated by tests that tend to correlate highly with overall intellectual function (i.e., tests of single word reading, such as the National Adult Reading Test ¹³ or the Wechsler Test of Adult Reading^12,¹⁴), or by administration of specific batteries designed to assess intelligence (including the Wechsler Intelligence Scales¹⁵ and Stanford-Binet Intelligence Test¹⁶). An intelligence quotient (IQ) is a derived score based on a patient’s performance on a number of different subtests. The Wechsler intelligence subtests are roughly divided into verbal and visual (performance-based) abilities, with the difference between these scales sometimes taken as a rough estimate of left (verbal) and right (visual) hemisphere functions. In addition to yielding a measure of general intellectual function, a patient’s performance on the different subtests can also provide important information or “clues” for the neuropsychologist as to where a patient’s area of difficulty might lie, and help guide the assessment itself. However, in and of itself, IQ alone is not diagnostically informative for neurologically impaired individuals, because it is sometimes insensitive to the selective cognitive impairments that can result from focal lesions (i.e., anterograde memory impairments). Nonetheless, IQ can play an important role in understanding the nature and extent of an individual’s deficits, and can be critical in understanding whether deficits are more global in nature.

Attention

The domain of “attention” is highly complex. It includes the ability to orient to a stimulus, to filter out extraneous information, and to sustain focus on a particular stimulus or activity. Its functions cannot be localized to a single anatomical brain region. Instead, attention is subserved by combinations, or “networks,” of brain structures. At the most basic level, specific midbrain structures (such as the reticular activating system) play a fundamental role in alertness and arousal. Subcortical structures (such as certain thalamic nuclei) play a role in selective attention, in that they serve as a gatekeeper for both sensory input and motor output. Limbic system structures (including the amygdala) also play an important role in designating the motivational significance of a stimulus. Finally, a number of cortical regions are involved in various aspects of attention, including spatial selective attention (the inferior parietal cortex ¹⁷), behavioral initiation and inhibition (orbital frontal region), sustained attention (anterior cingulate), task-shifting (dorsal lateral region), and visual search (frontal eye fields).^18,¹⁹

In light of the many brain structures involved in attentional processing, it is not surprising that impairments in attention are among the most common sequelae of brain damage. Some of the more common disorders in which attentional disturbances can be significant include ADHD, traumatic brain injury (TBI), stroke, dementing conditions (e.g., Alzheimer’s disease or frontotemporal dementia), and hydrocephalus. In addition to various neurological disorders, diminished attentional capacity is a common secondary feature of most psychiatric conditions, including affective and psychotic disorders.

The assessment of an individual’s attentional capacity is accomplished not only through the administration of standardized attentional tests, but also via clinical observation. In observing a patient’s behavior within both the clinical interview and the evaluation itself (i.e., test administration), the clinician obtains information regarding the patient’s level of attention (e.g., whether the patient is attending to examination questions or distracted by noises outside of the examination room).

Table 8-1 provides a summary of common measures used to assess various aspects of attention within a neuropsychological evaluation. Attentional capacity, which is also referred to as attention span, short-term memory span, or short-term memory capacity, denotes the amount of information that the individual’s attentional system can process at one time. This function is typically measured by span tests, where the patient is presented with increasingly larger amounts of information and is asked to repeat back what was heard or seen. Two of the most frequently used measures are Digit Span,¹⁵ where the patient repeats increasingly longer sequences of digits, and the visual analogue of this task, Spatial Span,¹⁵ where the patient repeats increasingly longer tapping sequences on randomly arrayed blocks. Working memory, the ability to manipulate information in short-term storage, is also typically assessed. For example, the patient may be asked to reverse digits or tapping sequences of increasing length, to rearrange randomly presented sequences into a specific order, or to mentally compute solutions to orally presented arithmetic problems. Information regarding a patient’s working memory capacity can potentially shed light on an individual’s deficits in other cognitive realms, such as the ability to successfully comprehend or encode complex information (e.g., an orally conveyed story, or a written passage).

Table 8-1 Assessment of Attention

Component Assessed	Measure	Example of Specific Test
Attentional capacity/short-term memory span	Digit span forward	WAIS-III¹⁵; WMS-3⁹⁶; or RBANS Digit Span⁹⁴
	Spatial span forward	WMS-3 Spatial Span; Corsi Block Test⁹⁷
Working memory	Digit span backward	WAIS-III; WMS-3
	Spatial span backward	WMS-3 Spatial Span; Corsi Block Test
	Letter-number sequencing	WAIS-III or WMS-3 Letter-Number Sequencing
Complex visual search and scanning	Symbol substitution	WAIS-III Digit Symbol Coding; Symbol Digit Modalities Test (SDMT)⁹⁸
	Visuomotor tracking	Trail Making Test—part A²⁷
Sensory selective attention	Cancellation	Visual Search and Attention Test⁹⁹; Letter and symbol cancellation tasks¹⁰⁰
	Visuomotor tracking	Trail Making Test—part A
	Line bisection
	Drawing and copying
	Reading
Sustained attention and task vigilance	Cancellation	(See above)
	Vigilance	Conners’ Continuous Performance Test (CPT)¹⁰¹
	Sustained and selective serial addition	Paced Auditory Serial Addition Test (PASAT)¹⁰²
Selective/divided attention	Sustained and selective serial addition	Paced Auditory Serial Addition Test (PASAT)
	Selective auditory tracking	Brief Test of Attention (BTA)²⁰
	Selective attention and response inhibition	Stroop Color and Word Test³⁴; D-KEFS Color-Word Interference Test³⁰

The assessment of attention also includes measures of a patient’s ability to orient to stimuli around the patient. Patients with lateralized lesions (such as those involving the parietal or temporal lobe) may display a hemi-inattention phenomenon whereby perceptual information that is presented on the side of the body contralateral to the lesion is ignored. A parietal lobe lesion may result in a unilateral visual or tactile inattention phenomenon, whereas a temporal lobe lesion (or lesion to the central auditory pathways) may cause unilateral auditory inattention.^17,¹⁸ For example, visual hemi-inattention, also referred to as unilateral visual neglect, typically results from lesions to the right posterior cortex (although it has also been reported following frontal lesions)⁷ and involves reduced awareness of visual information in the left side of space. The presence of visual inattention can be striking acutely following neurological insult (see Figure 8-2). Over time, the severity of neglect diminishes, and patients are left with a more subtle deficit in the registration of information in the left side of space when the stimuli are complex or when there is competing information on the right. Within a neuropsychological assessment, the most commonly used tests of visual inattention are cancellation tasks, where the patient is asked to detect targets in an array of visually similar stimuli. Other tests of visual neglect include line bisection tasks, drawing and copying tests (e.g., a clock face with numbers or a daisy), and reading tests (particularly useful when the elicitation of a motor [non-speech or other than speech] response is not possible, e.g., due to hemiparesis).

Vigilance, or the patient’s ability to sustain attention over time, is also assessed. Deficits in this aspect of attention are often observed in individuals with ADHD. The most commonly used testing paradigms involve the presentation of stimuli over time, with the patient instructed to respond when a prespecified stimulus (“target”) is presented. These tasks are also sensitive to impulsivity, with the neuropsychologist also assessing the patient’s ability to inhibit responding to nontarget stimuli.

Finally, measures that assess the patient’s ability to divide attention between competing stimuli are frequently given. In these tasks, the patient is typically presented with more than one type of stimulus (e.g., numbers and letters) and is asked to keep track of one of the stimuli. For example, the Brief Test of Attention (BTA) is a test in which the patient listens to strings of randomly ordered numbers and letters and is asked to track only how many numbers he or she hears.²⁰

Frontal/Executive Functions

“Complex” cognitive functions, which include executive functions, “social intelligence” (i.e., personality, comportment, and empathy), and motivation,²¹ are primarily mediated by the frontal lobes of the brain. Executive functions encompass a group of higher order cognitive functions (including the ability to plan and initiate behavior, to both maintain and suddenly shift from a behavioral set, to organize information, to self-monitor one’s responses, and to reason abstractly). Social intelligence is a term that has been used by various clinicians to describe such phenomena as the ability to modulate one’s emotions, to inhibit various impulses (e.g., aggressive, sexual), and to feel empathy for others. Finally, motivation can be described as the emotional and behavioral “drive” to initiate, persist with, and complete a specific goal.

Disruptions to one or more of the aforementioned complex cognitive functions are among the most frequently encountered deficits in the typical neuropsychological practice. This is not surprising when one considers that the frontal lobes are not only the largest region of the brain, making up more than one-third of the human cerebral cortex, but are also the most susceptible to the effects of aging and are among the most vulnerable to many causes of brain damage.⁷ The frontal lobes also have extensive connections to other regions of the brain. For example, a series of parallel, anatomically segregated neuronal circuits connect specific regions of the frontal cortex with subcortical brain structures (including the striatum, globus pallidus, substantia nigra, and thalamus).^22,²³ Three of these circuits mediate complex cognitive functions: a dorsolateral prefrontal circuit mediates executive functions, a lateral orbitofrontal circuit mediates social intelligence, and an anterior cingulate circuit mediates motivation. Thus, neurological disorders (such as Parkinson’s disease and Huntington’s disease) that affect subcortical structures can cause cognitive and behavioral impairments in much the same way as direct lesions to the frontal lobe. Included among the additional neurological disorders/types of neurological insults that commonly result in frontal/executive dysfunction are ADHD, TBI, stroke, and certain dementing illnesses (e.g., frontotemporal dementia or Lewy body disease).

The assessment measures that are used to evaluate dorsolateral, prefrontal, or “executive” functions are somewhat different from those used to assess other cognitive domains, due to the nature of this complex group of skills. Executive functions involve how a patient goes about doing a task (e.g., the ability to plan, to initiate behavior on a task, to organize an approach) and the extent to which the patient can be flexible in response to changing task parameters. Therefore, many of the measures that assess executive function present stimuli that are complex, unstructured, or open-ended in format (requiring the patient to determine how to organize, shift between, or categorize the stimuli).

A critical aspect of executive function is the ability to initiate and sustain behavior on a task. Fluency tests, where the patient is asked to generate rapid responses to a particular cue, are among the most commonly administered measures that assess this specific function. For example, within the verbal domain, patients are given a 1-minute period to generate as many words as they can that begin with a particular letter. Patients can experience difficulty with this task for different reasons. These include impaired ability to “get started” (i.e., task initiation), difficulty persevering for the full minute, difficulty generating different responses (evidenced as perseverative tendencies, with patients getting “stuck” on a particular response), or because of “loss of set” (i.e., losing track of the cue provided by the examiner). Letter fluency tasks are most sensitive to disruptions in executive function and are often observed in patients with frontal lesions ²⁴ or with subcortical dementing processes (such as Parkinson’s disease).²⁵ In many cases, the patient does better when provided with structure, such as a semantic cue (e.g., the patient is asked to list as many animals as possible). Note that tests of verbal fluency administered by the neuropsychologist differ from those given as part of physicians’ mental status screens in that, within a neuropsychological evaluation, the patient’s performance is compared against age- and education-based normative data. The significance of this normative data becomes apparent when one considers that the mean number of words provided for the letter fluency task (F-A-S test) is 38.5 for a 20-year-old versus 25.3 for a 75-year-old.²⁶ Nonverbal analogues to measures of verbal fluency include measures of design fluency (e.g., where the patient is asked to draw as many different designs as possible within an allotted time).

Cognitive flexibility refers to the ability to shift to an entirely separate task or to alternate between different stimuli. One of the most commonly used and widely recognized measures of cognitive flexibility is Part B of the Trail-Making Test ²⁷ (Figure 8-3). This task involves the rapid alternate sequencing of numbers and letters that are randomly arrayed on a page. Cognitive flexibility is also assessed on set-shifting fluency tasks (e.g., asking the patient to alternately provide items from two different categories), as well as on problem-solving measures (such as the Wisconsin Card Sorting Test),²⁸ where the patient needs to be responsive to changing corrective feedback in determining card-sorting strategies. A large number of perseverative errors in the face of persistent negative feedback is highly indicative of frontal system impairment.

Figure 8-3 Trail Making Test, Part B.²⁷ This test provides a measure of set shifting, with the patient asked to rapidly connect numbers and letters in alternating fashion. Performance on Part B is compared to Part A, which includes only numbers that the patient is asked to rapidly connect in sequence.

(From Reitan RM, Wolfson D: The Halstead-Reitan Neuropsychological Test Battery, Tucson, AZ, 1985, Neuropsychology Press.)

Planning and organization also are crucial aspects of executive functions (Table 8-2). Tower tasks (e.g., Tower of London Test,²⁹ DKEFS Tower Test³⁰) assess spatial planning and rule-learning skills. Organizational strategies can be inferred by observing the patient’s approach, particularly to tasks in which the stimulus presented is complex or unstructured in its format. For example, information regarding the patient’s organizational ability is gleaned through examining the degree to which the patient clusters randomly ordered words according to their semantic category membership on list-learning tasks (such as the California Verbal Learning Test–II).³¹ A patient’s approach to copying a complex figure (e.g., the Rey Osterrieth Complex Figure Test,³² Figure 8-4) also provides information regarding organizational ability. The neuropsychologist examines the extent to which the patient appreciates and uses the figure’s structural elements (e.g., large outer rectangle, intersecting diagonals) in copying the design, or instead, relies on a fragmented or seemingly haphazard approach (Figure 8-5, Example A).

Table 8-2 Assessment of Frontal/Executive Functions

Component Assessed	Measure	Example of Specific Test
Initiation and maintenance of a complex task set; generation of multiple response alternatives	Verbal fluency	Controlled Oral Word Association Test (COWAT)²⁶; D-KEFS Verbal Fluency Test
	Design fluency	Ruff Figural Fluency Test¹⁰³; Five-point Test¹⁰⁴; D-KEFS Design Fluency Test
Cognitive flexibility	Visuoconceptual tracking	Trail Making Test—part B; D-KEFS Trail Making Test
	Card sorting	Wisconsin Card Sorting Test²⁸ (See above)
	Verbal fluency
Organization/planning	Spatial organization and planning	Rey-Osterrieth Complex Figure Test³²; Tower of London Test²⁹; D-KEFS Tower Test
	Use of semantic clustering strategies on verbal learning tasks	California Verbal Learning Test (CVLT-II)³¹
Concept formation and reasoning	Proverb interpretation	D-KEFS Proverb Test
	Verbal conceptualization	WAIS-III Similarities; Mattis DRS Conceptualization⁸¹
	Nonverbal concept formation	The Category Test¹⁰⁵
	Matrix reasoning	WAIS-III Matrix Reasoning; Raven’s Progressive Matrices³³
	Card sorting	Wisconsin Card Sorting Test (WCST); D-KEFS Sorting Test
Behavioral inhibition	Selective attention and response inhibition	Stroop Color and Word Test; D-KEFS Color-Word Interference Test
	Go/no-go
	Behavioral ratings (self-report and/or family-report)	Frontal Systems Behavior Scale (FrSBe)³⁵
Apathy	Behavioral ratings (self-report and/or family-report)	Frontal Systems Behavior Scale (FrSBe)