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Understanding Cognitive Dysfunction in Multiple Sclerosis: Integrating a First-person Perspective With Neuropsychological Testing, Neuroimaging, and Cognitive Neuroscience Research

Courtney, Susan M. PhD*,†

Cognitive And Behavioral Neurology: December 2011 - Volume 24 - Issue 4 - p 227–230
doi: 10.1097/WNN.0b013e3182400847
First-Person Case History and Commentary
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This paper gives perspectives on a companion article, the case history of a professional writer who has multiple sclerosis. The patient’s first-person account of her illness is combined with clinical summaries about her care. The discussion of this case illustrates the value of combining such subjective and objective reports in evaluating a patient. Furthermore, considering these reports in the context of current research findings on the organization and function of cognitive neural systems can shed light on patients’ seemingly contradictory clinical findings. For this patient, a deficit in the ability to select the most important information to achieve her current goals reflected her neuropsychological test results and neuroradiologic findings, and helped to explain her difficulties with her job and her activities of daily living. Because the patient’s cognitive impairments have been her primary manifestations of multiple sclerosis, she illustrates the importance of physicians attending to and helping patients manage their cognitive deficits.

*Departments of Psychological & Brain Sciences

Neuroscience, Johns Hopkins University; F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD

This work was supported in part by NIH Grant R01 MH082957 to S.M.C. and by the National Multiple Sclerosis Society through a Daniel Haughton Senior Faculty Award (SF1752-A-1) made possible by a grant from the Brodsky Family Foundation.

The author declares no conflicts of interest.

Reprints: Susan M. Courtney, PhD, 204 Ames Hall, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218 (e-mail: courtney@jhu.edu).

Received October 31, 2011

Accepted October 31, 2011

There is often a disconnect between a patient’s self-report of cognitive abilities and the findings of formal cognitive testing. Introspection about one’s own cognitive abilities is notoriously unreliable. Further, depression or anxiety can cloud an individual’s judgment. However, some first-person accounts are more telling than neuropsychological testing. A self-report may be particularly valuable to a professional evaluating the person’s quality of life, employability, and independence in activities of daily living. Furthermore, when we systematically integrate information gained from a first-person account with neuropsychological and neuroradiologic data, the whole can be greater than the sum of the parts. The case study of the woman referred to as “N.L.,” presented in the companion article in this issue,1 demonstrates some of the insights that can be gained.

At the time of the writing of her case study, “N.L.” was in her 50s and living with multiple sclerosis (MS). Before her diagnosis, she had graduated cum laude from law school, worked as a health care attorney, and become a professional writer. She has published numerous legal briefs, law reviews, and several dozen books. Her neuropsychological evaluation, performed about 8 years after her diagnosis, revealed very good verbal skills and “no indication of any dysnomia, dysarthria, dyslexia, nor spelling dyspraxia.” Indeed, her written first-person account of her cognitive symptoms is, for the most part, lucid, detailed, and well organized. However, she states that it takes her much longer to write such types of documents than it used to—so long that she is no longer able to work as a full-time writer. She finds this difficulty “the most troubling of the cognitive problems I have experienced as a result of having MS.”

One fairly obvious explanation for the discrepancy between N.L.’s self-assessment and her test results is the difference in perspective between first-person accounts and formal testing. She cannot help but compare her current cognitive abilities to her previous abilities. Although a skilled neuropsychologist tries to take previous abilities into account in a formal cognitive assessment, such judgments must almost always be based only on indirect measures like educational achievement and profession. Test scores, however, are reported in terms of the percentile ranking relative to the patient’s peer group. It is rare for a tester to know what the patient’s premorbid ranking would have been.

As one of N.L.’s strongest skills, writing was the focus of her daily activities and livelihood. If we think of writing as a verbal process and thus expect the verbal subtests of the neuropsychological evaluation to reflect her current writing ability, we might conclude in light of her professional history that N.L.’s writing skills had fallen from exceptional to above average. N.L. would certainly consider this a significant loss. We should also suspect that the loss reflects disease progression. A physician should take such a finding into account when planning treatment, particularly for someone like N.L., who has few sensory and motor impairments. However, we would not necessarily label someone who retains above-average skills as having a clinical “impairment” or “disability.”

Consider, however, that writing is a complex cognitive process that involves elements that are not exclusively verbal. Particularly the kind of writing that N.L. has done requires planning, logical reasoning, organization, and selective attention. These skills may serve both verbal and nonverbal processing. They are also difficult to assess in neuropsychological testing because patients may have found ways to compensate for some of their deficits. We should evaluate N.L.’s writing problems in the context of the other significant cognitive impairments—and preserved functions—revealed by her neuropsychological testing, the MS-related damage shown by her magnetic resonance imaging (MRI) scans, and the other daily life challenges that she describes in her account. We should also consider all her data in the context of the latest research on the neural basis of these cognitive functions. In this way, a clearer and a more coherent picture emerges.

MS can cause deficits in specific cognitive functions that are localized to brain areas affected by individual lesions. One person might have trouble with getting lost while driving in unfamiliar neighborhoods, whereas another could have trouble remembering what particular words mean or how they are spelled. The result can be a constellation of unrelated individual cognitive impairments, similar to the common experience in those with MS of a constellation of unrelated sensory and motor impairments, such as weakness in the right leg and blindness in the left eye. More frequently, however, the cognitive impairments seen in those with MS are the result of disruptions in processes such as attention and working memory,2–4 which are known to depend on rapid, precise, reciprocal interactions among multiple brain regions and networks.5,6 These processes seem to be somewhat hierarchically organized,7 with more complex or abstract abilities depending on the integration of multiple simpler components. This dependency among cognitive processes complicates attempts to ascertain precisely where the system has broken down.

In N.L.’s case, consideration of the domain-specific and hierarchical organization of the neural systems involved in working memory and attention can help to explain her experience. The real-world examples that she reports about difficulties with short-term memory seem to be almost exclusively verbal. For example, when researching downloaded scholarly articles, she cannot remember simultaneously the author name, title, and publication date for the few seconds that it takes to type them into a database. To recall a specific fact from long-term memory, she reports using visual imagery to supplement her verbal memory. For example, to remember the title of the last book she read for pleasure, N.L. visualizes that book on the dresser in the bedroom where she usually kept it. However, her neuropsychological testing produced verbal subtest scores that were substantially higher than her nonverbal subtest scores. She scored below average on only 2 subtests of auditory/verbal attention and concentration, whereas most verbal subtests were in the above-average or even superior range. On the other hand, some of her nonverbal tests indicated moderate to severe impairment (scores range from the 2nd to 66th percentile). At first glance, then, the first-person account and the testing results seem to contradict each other regarding whether her verbal or visual processes are more impaired.

Part of the explanation may lie in the neuropathology of MS and the fine structure of the functional organization of both the verbal and visual neural systems. There is evidence for functional specialization within each of these systems. For example, there seem to be separate cortical regions specialized for the active representation and processing of different types of verbal information, such as phonological, semantic, and syntactic.8 There are also separate regions with preferential tuning for different types of visual stimulus categories, such as faces, spatially structured environments, and written words.9,10 Unlike stroke, which usually destroys a single large swath of cortex, MS damage is patchy and incomplete. It may affect the processing of certain kinds of verbal or visual information, but not others. Furthermore, as the lesions, particularly in early stages of the disease, involve inflammation and demyelination of white matter connections, and do not necessarily destroy an area or its connections, deficits may be evident only on certain types of tasks, such as those that require rapid processing of the affected information.11

In contrast, the hierarchical, interdependent organization of these highly specialized domain-specific regions means that some symptoms that seem at first to be completely unrelated may, in fact, stem from impairment of a single cognitive subprocess. Take, for example, the description in N.L.’s first-person account of the particular types of challenges that she has encountered with writing, and her error of waiting in line at the market fish counter to order turkey burgers. These seem like completely unrelated tasks, but the problem in completing both successfully may stem from a common deficit in selecting the information that is most important for achieving her current goals in the current context. In describing her difficulties with writing, she states, “I think that if I could write now, the quality of both the ideas and their expression would be about the same. It is the processes of writing itself that is [sic] at issue.” She also describes similar problems when she tries to communicate the same ideas by speaking instead of writing, so it does not seem to be a problem with writing per se. The process of writing requires N.L. to keep in working memory the overall communication goal of the project and to select the relevant (currently most important) information for the context of each paragraph and sentence. Similarly, in order to choose to stand in the line at the meat counter rather than the fish counter, she must recognize that the meat counter is more relevant (more related) to reaching her current goal (to buy turkey burgers), and act on that realization. In other words, this process requires her to maintain an active pattern of neural activity that holds information about her goal in short-term memory, and to enable that information to bias her attention and actions to the option that is most likely to lead to achieving that goal.

This interpretation of N.L.’s difficulties in writing and other activities of daily living—as stemming from a deficit in her ability to select the information that is most important for her current context and goals—is also consistent with the damage revealed in her MRI scans. Her scans reveal numerous MS lesions in the anterior prefrontal and parietal white matter. She also seems to have moderate atrophy of the parietal cortex. In addition, there are extensive lesions in and atrophy of the corpus callosum.

These brain areas and their connections are precisely those that are needed to select and use the most important information to achieve one’s goals. Particularly important are interactions of the anterior prefrontal cortex and parts of the parietal cortex with ventral temporal cortex or other regions in which patterns of neural activity represent particular pieces of information that are relevant to the current task.12 The anterior lateral prefrontal cortex is considered by some to sit at the top of a prefrontal hierarchical system.13 It has been implicated in processing and maintaining abstract, integrated, and/or relational information and in subgoal processing.14–17 This part of prefrontal cortex may maintain a pattern of neural activity that carries information about what the current task or goal is, and its relationship to other tasks, rules, or goals. Other parts of dorsolateral prefrontal cortex seem to be involved in switching tasks, shifting attention, or updating information in working memory when the situation changes and something else becomes more important.18–20 Lesions in the corpus callosum would affect the ability of both the prefrontal and parietal cortices to access, integrate, and switch among the many types of information, all of which might be important to the task but stored in distant brain regions in different hemispheres.

A deficit in the ability to select currently important information would also be consistent with some aspects of N.L.’s neuropsychological test results, which showed a disproportionately large impairment with complex verbal lists, abstract reasoning, and cognitive flexibility. Complex verbal lists and abstract reasoning require organization (such as “chunking”21,22) of large amounts of information, by selecting and using specific aspects of that information. For example, when writing a book, one must organize the many themes into chapters and many specific facts and arguments of a chapter into paragraphs. Cognitive flexibility requires the ability both to maintain and to switch attention from one mental representation to another when the criteria for what is important change because of a change in feedback, goals, or context, for example, when starting to write a new paragraph. Again, these processes require interactions between the anterior prefrontal cortex and the parietal cortex, and among these regions and many, many others along long-range white matter tracts. Of course, lesions near the anterior prefrontal or parietal cortices would disrupt this communication, but so would lesions anywhere along the length of these tracts. The multifocal nature of MS makes it likely that these complex circuits will be disrupted in at least 1 location, reducing the effectiveness of the entire system. Thus, N.L. is not alone. Many people with MS face similar challenges with impairments in these sorts of higher cognitive functions that depend on rapid, precise interactions among multiple brain areas along extensive white matter networks.

Unfortunately, many physicians do not test for or even inquire about the cognitive difficulties that their patients with MS may be experiencing. These physicians may assume that they can judge their patient’s disease progression from sensorimotor symptoms and MRI scans alone. Many physicians also assume that while they might have drugs or exercises to offer for relief of sensorimotor symptoms, there is little that can be done for cognitive symptoms. Why spend time and money on something that will not change the course of treatment?

On the contrary, N.L.’s first-person account of her experiences dramatically illustrates that cognitive impairment in MS can progress independently of physical symptoms and can have a significant impact on employability and activities of daily living. Her account also illustrates how support from physicians, family, and other sources is essential to living successfully with MS-related cognitive changes. N.L. found jobs whose schedule and work environment were adaptable to her abilities. For people like N.L. who have relapsing-remitting MS, both cognitive and physical abilities can change dramatically from 1 day to the next. Thus, employers, family members, and the person living with MS may need to be educated to develop flexible expectations.

People may also need to learn new ways to approach a task. Many of us have always needed to use outlines and lists to write a coherent document, even before any impact of age or disease. N.L. discovered on her own that while she may not have needed these tools before MS took its toll, they became useful as her disease progressed. If the person with MS, her physician, and her rehabilitation therapist understand precisely which of her cognitive abilities are strong and which are weak, they will be better able to identify the accommodations and adaptations that might be helpful and develop a targeted cognitive rehabilitation program. This understanding will come from integrating all available information, including first-person accounts, neuropsychological testing, neuroimaging data, and the latest research on the functional organization of cognitive neural systems.

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ACKNOWLEDGMENTS

The author would like to thank Drs Peter Calabresi, Douglas Kerr, Justin McArthur, Benjamin Greenberg, Daniel Harrison, and all the other neurologists at the Johns Hopkins Multiple Sclerosis Center for their tutelage and research collaboration.

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Keywords:

multiple sclerosis; prefrontal; parietal; attention; working memory

© 2011 Lippincott Williams & Wilkins, Inc.