Normalizing Memory Recall in Fibromyalgia With Rehearsal: A Distraction-Counteracting Effect

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1 Arthritis & Rheumatism (Arthritis Care & Research) Vol. 61, No. 6, June 15, 2009, pp DOI /art , American College of Rheumatology ORIGINAL ARTICLE Normalizing Memory Recall in Fibromyalgia With Rehearsal: A Distraction-Counteracting Effect FRANK LEAVITT AND ROBERT S. KATZ Objective. To examine the impact of distraction on the retention of rehearsed information in patients with fibromyalgia syndrome (FMS). Methods. Data refer to the neurocognitive examination of 134 patients (91 with FMS and 43 control subjects) presenting with memory loss. Four neurocognitive measures free of distraction, along with 2 measures with added distraction, were completed. Differences in the retention of rehearsed and unrehearsed information with a source of distraction present were calculated. Results. Patients with FMS showed normal cognitive functioning on verbal memory tests free of distraction. Adding a source of distraction caused unrefreshed information to be lost at a disproportionate rate in patients with FMS. Over 87% of patients with FMS scored in the impaired range on a task of unrehearsed verbal memory. Adding a source of distraction to well-rehearsed information produced a normal rate of recall in FMS. Conclusion. Rehearsal mechanisms are intact in patients with FMS and play beneficial roles in managing interference from a source of distraction. In the absence of rehearsal, a source of distraction added to unrefreshed information signals a remarkable level of cognitive deficit in FMS that goes undetected by conventionally relied-upon neurocognitive measures. We present a theory to promote understanding of the cognitive deficit of people with FMS based on reduced speed of lexical activation and poor recall after distraction. INTRODUCTION Cognitive distraction plays a critical role in short-term memory loss in people with fibromyalgia syndrome (FMS) (1). In recent research, exposure to a source of distraction stood out as the central cause of rapid forgetting in people with FMS. Adding a source of distraction to a standard memory task eradicated verbal information memory at a disproportionately high rate in people with FMS. In fact, people with FMS lost new verbal information at a rate that was 44% greater than an age-matched control group presenting with memory problems, and was almost 3 times greater than the normative sample (1). In the absence of distraction, short-term verbal memory is normal in people with FMS. Very little is known about why the costs of distraction are so high in people with FMS. People with FMS show a prominent disturbance in cognitive performance on the Auditory Consonant Trigram Frank Leavitt, PhD, Robert S. Katz, MD: Rush Medical College, Chicago, Illinois. Address correspondence to Frank Leavitt, PhD, 513 Illinois Road, Wilmette, IL frankleavitt@ sbcglobal.net. Submitted for publication December 25, 2008; accepted in revised form March 3, (ACT) test (1). Properties of the ACT permit an evaluation of severe forgetfulness in FMS that is rooted in the prevention of rehearsal of information by competition from a source of distraction (2). The ACT paradigm entails remembering a 3-item list (a trigram) of consonant letters after attending to a distracting, unrelated task. Between hearing the trigram and recall, subjects count backwards by threes (the distracter task) from a predetermined number for intervals of 9, 18, or 36 seconds. Diverting attention to an unrelated cognitive operation involving serial subtraction prevents rehearsal of the 3 consonant letters. When an unrelated cognitive operation (a distraction) disrupts the encoding of auditory information, the unrehearsed information is forgotten almost twice as fast by individuals with FMS (1). Why a source of distraction disproportionately hinders later recall of unrehearsed information in people with FMS is unclear. A natural question is whether interference created by a source of distraction impacts differently when the information to be remembered has been rehearsed. The objectives of this study were to replicate previous cognitive findings relating cognitive impairment to distraction while recalling unrehearsed information in people with FMS, and to determine whether distraction impairs the retention of rehearsed information in a similar fashion. 740

2 Effects of Distraction and Rehearsal on Memory in FMS 741 PATIENTS AND METHODS Patients. Archival data were drawn from the records of 91 women with FMS who consecutively presented for the evaluation of memory problems by neurocognitive examination on the basis of clinical referral. The women in the sample fulfilled the American College of Rheumatology criteria for the classification of fibromyalgia (3). The diagnosis was established by a rheumatologist and was based on widespread pain in combination with tenderness of 11 of 18 specific tender point sites (3). The control sample consisted of 43 women without FMS presenting with memory problems, who were examined during the same time period. The control sample was similar to the FMS group in terms of age and education (mean SD age was years and years, respectively, and the mean SD education was years and years, respectively). Among the controls, 5 reported a history of seizures/epilepsy, 4 reported a history of head trauma or transient ischemic attack, and 3 reported hypothyroidism, substance abuse, or obstructive sleep apnea. The inclusion criteria were that all participants should be age years, be female, and be fluent in English. The exclusion criteria were a history of drug or alcohol abuse, psychiatric treatment in the past 3 years, auditory impairment that might interfere with cognitive testing, or a lack of fluency in English. Patients with FMS reported a median length of memory problems of 20 months (range 1 month to 18 years); 41% percent reported memory problems 1 year in duration. By comparison, controls reported a median length of memory problems of 18 months (range 1 month to 22 years); 36% reported memory problems for 1 year in duration. Differences were not statistically significant (P 0.05). Measures. The Logical Memory and Paired Associates subtests of the Wechsler Memory Scale, Third Edition assess memory performance free of stimulus competition at encoding (4). The Logical Memory subtest entails remembering 2 story paragraphs, with recall tested immediately and then after a 30-minute delay. Each paragraph contains 25 segments, and the score is the number of segments recalled. The Paired Associates subtest assesses formation of associations between 8 word pairs, some unrelated (e.g., truck/arrow), over 4 learning trials with cued recall tested after each trial (4). The scores are the sum of word pairs recalled over the 4 trials in addition to a 30-minute delayed cued recall trial. The ACT entails remembering 3-item lists (trigrams) of consonant letters after performing a distracting task that interferes with the input and encoding of new information (the trigram) (2). Immediately after hearing the trigram, subjects count backwards by threes (the distracter task) from a number for intervals of 9, 18, or 36 seconds, followed by free recall of the trigram. Five trials at each distracter interval are administered, along with a no-distraction condition (0 seconds). The maximum score for each interval is 15. The Rey Auditory Verbal Learning Test (RAVLT) (5) is a word list learning task consisting of 5 verbal presentations of a 15-word list of nouns (list 1) with free recall following each presentation. Thus, in this part, subjects rehearse the list information 5 times. Next, a distracter list of 15 nouns (list 2) is read, followed by free recall. On the postdistraction trial, the subject is asked to recall the first list (list 1). Four scores are reported: a summary learning measure (the total words recalled on the first 5 presentations), a predistraction measure (the number of words recalled on trial 5), a postdistraction measure (the number of words recalled from list 1 after distraction), and an interference measure (the difference between scores on the predistraction and postdistraction trials). The vocabulary subtest of the Wechsler Adult Intelligence Scale, Revised served as an estimate of general intelligence (4). Participants provided definitions of words presented in the order of increasing difficulty. The Beck Depression Inventory II, a 21-item, 4-point self-report scale, was used to measure symptoms of depression (6). Statistical analysis. Differences in memory performance between the 2 groups were analyzed. Mean SD was used to define the demographic and clinical features of the 2 groups. To assess group differences on the neurocognitive measures, we used a multivariate analysis of covariance with the 5 neurocognitive measures as the dependent variables; the clinical groups as the betweensubject variable; and age, education, vocabulary knowledge, and depression as covariates. With a significant overall multivariate effect, univariate effects were examined to assess differences between the groups on individual cognitive tests. Categorical variables were compared with Pearson s chi-square test. For RAVLT continuous variables, comparisons were made using the Student s 2-tailed t-test. P values less than 0.05 were considered statistically significant. RESULTS The cognitive performance of the 2 groups along with the age-appropriate normative values are shown in Table 1. Test scores are expressed in scale scores rather than raw scores to enable direct comparison of the level of performance across different tests. The mean SD standardized normative mean score for each test is On cognitive measures free of distraction, patients with FMS performed essentially at the normative mean. By contrast, they performed significantly below the established normative value on the measure with a source of distraction (ACT score 2.5 SDs below the normative mean). Patients with FMS recalled information on distractionfree measures better than controls on both Logical Memory paragraphs and the Paired Associates. On both measures, patients with FMS recalled more information immediately after exposure, as well as following a 30-minute delay. By contrast, on a measure involving unrehearsed information and a source of distraction, the patients with FMS recalled significantly less information on the ACT than the controls recalled.

3 742 Leavitt and Katz Table 1. Mean summary data and percentage of impaired scores in patients with fibromyalgia and age-matched controls presenting with memory problems* Mean summary data Impaired scores, no. (%) Memory test Standardized normative mean FMS group Control group FMS group Control group No distraction (WMS-III) Logical memory (9.9) 13 (30.2) Logical memory, delayed (7.7) 10 (23.2) Paired associates (12.1) 11 (25.6) Paired associates, delayed (8.1) 13 (30.2) With distraction (ACT test) (87.9) 20 (46.5) * Values are the mean SD unless otherwise indicated. FMS fibromyalgia syndrome; WMS-III Wechsler Memory Scale, Third Edition; ACT Auditory Consonant Trigram. P Adjusted for age, education, vocabulary, and depression. P P P The proportion of scores falling in the impaired range for each group on each neurocognitive test is shown in the right panel of Table 1. Impairment was defined as scores 1.67 SDs below the age-appropriate normative mean (below the fifth percentile). These data show that the cognitive performance of patients with FMS was disproportionately impaired by distraction. Collectively, 87.9% of patients with FMS scored in the impaired range on the ACT. This proportion was significantly higher than the proportion found in the control sample. By contrast, the great majority of patients with FMS were functioning at normal levels on the 4 measures that were free of distraction. Impairment on these measures ranged from a low of 7.7% on Logical Memory delayed recall to a high of 12.1% on Paired Associates. Differences in the groups recall of the RAVLT 15-item word list are presented in Table 2. On average, total recall across 5 presentations was 5 words greater in the FMS group. Recall at the fifth presentation trial (predistraction trial) was also significantly higher in the FMS group. The difference between trial V and trial VI represents the effects of having been distracted by the introduction of a second word list (list 2). Both groups recalled fewer words after the presentation of a distracter word list, but the mean postdistraction loss was equivalent in the 2 groups. The postdistraction information loss was small, 2 words. No significant differences from reference norms (mean SD score ) were noted for the postdistraction trial, indicating that a source of distraction did not greatly interfere with the recall of information rehearsed over 5 trials. DISCUSSION Rehearsal mechanisms are intact in patients with FMS, and play a beneficial role in managing a source of distraction. The retention of repeated information interrupted by a source of distraction is normal in patients with FMS, indicating that distraction does not disrupt memory for well-rehearsed information in patients with FMS. Patients with FMS forget well-rehearsed information at a rate that is very similar to a healthy population following a distraction. Data of this nature imply that rehearsal counteracts interference from a source of distraction. One way to support memory in patients with FMS may be added rehearsal. Our results confirm previous findings and provide compelling evidence that deficits in the management of distraction are an important feature of cognitive dysfunction in FMS (1). As measured by the ACT, which provides a distraction task that prevents rehearsal between auditory presentation of information and recall (7), short-term memory for verbal information that is unrefreshed by rehearsal is significantly impaired in patients with FMS. In the aggregate, psychometric-based evidence of cognitive abnormality was found in 87.9% of patients with FMS. As a group, people with FMS performed 2 SDs below the normative score for their age on the ACT, highlighting their incapacity to retain unrefreshed information when their attention is split between relevant and distracting information. Adding a source of distraction to neurocognitive testing is critical to the objective demonstration of significant memory problems in people with FMS. Table 2. Group differences on recall and distraction trials of the Rey Auditory Verbal Learning Test Group Total words recalled, trials I V Predistraction, trial V Postdistraction, trial VI Difference, trial VI trial V* Fibromyalgia syndrome, mean SD Control, mean SD * Normative mean SD difference P P 0.05.

4 Effects of Distraction and Rehearsal on Memory in FMS 743 Table 3. Differences in the time course of information transmission from presentation of sensory information of a 3-second duration to short-term memory in the neural networks of the participant groups, and their impact on the strength of the memory trace sent into long-term memory Group Time consumed in lexical storehouse Time available for processing information in short-term memory Output from short-term memory Fibromyalgia syndrome 620 msec* 2 minutes, 380 msec Weak memory trace Control 417 msec 2 minutes, 583 msec Strong memory trace * 203 msec represents the extra consumption of time in the lexical storehouse (620 msec 417 msec 203 msec) in fibromyalgia. Abnormalities in memory among patients with FMS may be missed because measures traditionally relied upon for neurocognitive examination fail to include a source of distraction (8). On 4 such measures of verbal memory, patients with FMS demonstrated auditory memory skills equal to those of the average, healthy adult. On distractionfree measures, patients with FMS resembled the controls on both immediate and delayed recall of both narrative and unstructured verbal information. The fact that patients with FMS can lay down new memories at an age-appropriate rate in conditions free of distraction suggests that some parts of memory work well when dealing with one source of information at a time. Results in the normal range on measures conventionally relied upon to assess auditory memory functions imply that primary encoding and retrieval mechanisms are intact. We envisage the culprit of poor recall in people with FMS as a weak memory trace brought on by reduced processing time, and maintained by distraction that prevents rehearsal of relevant information. In support of this hypothesis, we turn to a timing deficit uncovered among people with FMS, specifically slow naming speed (9). Naming comes so naturally that we forget that naming speed is determined by the time course of lexical activation, which is why naming speed has become a common tool in estimating lexical speed (10,11). Faster naming speed is associated with faster lexical activation, and generally reflects the amount of time consumed in probing the lexical system for matching mental representations (12), which is a crucial stage in transforming letter strings into a recognizable word form. Knowledge stored in the lexical system derives from a buildup of mental traces linked to previous exposure to stimuli (13). The more time needed to find the best-matching lexical trace for word identification, the less time available for processing information at the next stage (14). People with FMS typically take more time to name words, implying reduced speed of lexical activation. In fact, the average deficiency in word-naming speed in people with FMS is 203 msec (Table 3) (9). The extra consumption of time delays the flow of information from the lexical stage to the next stage. It is as though a 203-msec time delay is put on information entering the short-term memory bank of individuals with FMS, thus shortening the time available to lay down a memory trace by 203 msec. The implication is that 3 seconds of incoming information processes as a second stimulus (Table 3). Without this built-in delay of 203 msec, processing takes place over seconds in short-term memory. The longer that information is processed in short-term memory, the stronger the memory trace will be (15). The presumption is that built-in delays operate to shorten processing time, causing individuals with FMS to lay down weaker memory traces (15). Adding a source of distraction following a 3-second presentation of the stimulus adds to the difficulty by preventing rehearsal of the primary information, sending weaker memory traces into long-term memory without any chance of solidifying memory traces by rehearsal (16). Presumably, distraction is more disruptive to individuals with fibromyalgia because their memory traces have not built sufficient velcro to stick in memory on their own (17). Adding rehearsal practice seemingly makes up for losses in processing time and creates a durable memory trace that is available for later recall and less affected by distraction. Presumably, another way to support recall in people with FMS is to alter lexical processing to work more quickly. Our theory is also capable of describing the phenomenon known as fibrofog (18). Sensory information enters and leaves the lexical storehouse millions of times a day. Recurrent time lags, further disrupted by outside distractions, may distort the synchrony of communication in neural transmission of information, thus forming the basis for the blurring of mental clarity commonly referred to as fibrofog. There were several limitations to this study. First, 3 subjects in the control sample did not meet full exclusionary criteria. However, data analysis without these 3 control subjects did not change the statistical results in any significant way. Second, cognitive test performance was not subjected to effort testing; however, suboptimal effort is unlikely to account for inferior test performance on the ACT. Deficits among patients with FMS are selective and occur in the context of normal test performance on the majority of the cognitive measures administered. Finally, variables such as sleep disruption, fatigue, and pain can affect cognitive performance but were not measured in this study. Future research should be directed toward the contribution of these factors in explaining differences between FMS and control groups. AUTHOR CONTRIBUTIONS All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors ap-

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