Effect of methylphenidate on oculomotor function in individuals with multiple sclerosis: a pilot randomized placebo-controlled trial.

Introduction: Individuals with multiple sclerosis (MS) frequently experience visual and oculomotor symptoms that may impact and confound neuropsychological assessments of information processing speed (IPS). In this study, we examined the effect of the psychostimulant methylphenidate on oculomotor function and the association between change in oculomotor speed and change in information processing speed. Methods: We used a repeated measures crossover design in which a sample of 11 participants with MS were randomly assigned to one of two treatment arms: one that received methylphenidate for 4 weeks and another that received a placebo for 4 weeks. After a 7-day washout period, the treatments were crossed over. The King Devick test, the Symbol Digit Modalities Test, and the Paced Auditory Serial Addition Test were administered at baseline and after each of the two study arms. Results: We found a significant improvement in oculomotor speed in the methylphenidate condition as compared to placebo. This improvement was significantly correlated with improvement on a visuomotor assessment of IPS (Symbol Digit Modalities Test), but no such association was found for an auditory-verbal assessment of IPS (Paced Auditory Serial Addition Test). Discussion: These findings suggest that individuals with MS experience improved oculomotor speed while taking methylphenidate, which may, in turn, improve performance on assessments of IPS with visuomotor demands.

Behavioral Interventions to Improve Sleep Outcomes in Individuals With Multiple Sclerosis: A Systematic Review.

BACKGROUND: Sleep disturbances are common in individuals with multiple sclerosis. The objective of this systematic review was to determine effective behavioral interventions to improve their sleep. METHODS: Literature searches were performed in December 2021 in Ovid MEDLINE, Elsevier Embase, and Web of Science, along with hand searching for grey literature and cited references. Four reviewers independently reviewed titles and abstracts (2 reviewers for each article; n = 830) and the full-text articles (n = 81). Consensus for inclusion was achieved by a fifth reviewer. Thirty-seven articles were eligible for inclusion. Four reviewers extracted relevant data from each study (2 reviewers for each article) using a standard data extraction table. Consensus was achieved for completeness and accuracy of the data extraction table by a fifth reviewer. The same 4 reviewers conducted a quality appraisal of each article to assess the risk of bias and quality of the articles, and consensus was achieved by a fifth reviewer as needed. Descriptive data were used for types of interventions, sleep outcomes, results, and key components across interventions. RESULTS: Overall, the cognitive behavioral therapy for insomnia, cognitive behavioral therapy/psychotherapy, and education/self-management support interventions reported positive improvements in sleep outcomes. Quality appraisal scores ranged from low to high, indicating potential for bias. CONCLUSIONS: Variability in the intervention type, intervention dose, outcomes used, training/expertise of interventionist, specific sample, and study quality made it difficult to compare and synthesize results. Further research is necessary to demonstrate the efficacy of most of the interventions.

Associations between smartphone keystroke dynamics and cognition in MS.

Objective: Examine the associations between smartphone keystroke dynamics and cognitive functioning among persons with multiple sclerosis (MS). Methods: Sixteen persons with MS with no self-reported upper extremity or typing difficulties and 10 healthy controls (HCs) completed six weeks of remote monitoring of their keystroke dynamics (i.e., how they typed on their smartphone keyboards). They also completed a comprehensive neuropsychological assessment and symptom ratings about fatigue, depression, and anxiety at baseline. Results: A total of 1,335,787 keystrokes were collected, which were part of 30,968 typing sessions. The MS group typed slower (P < .001) and more variably (P = .032) than the HC group. Faster typing speed was associated with better performance on measures of processing speed (P = .016), attention (P = .022), and executive functioning (cognitive flexibility: P = .029; behavioral inhibition: P = .002; verbal fluency: P = .039), as well as less severe impact from fatigue (P < .001) and less severe anxiety symptoms (P = .007). Those with better cognitive functioning and less severe symptoms showed a stronger correlation between the use of backspace and autocorrection events (P < .001). Conclusion: Typing speed may be sensitive to cognitive functions subserved by the frontal-subcortical brain circuits. Individuals with better cognitive functioning and less severe symptoms may be better at monitoring their typing errors. Keystroke dynamics have the potential to be used as an unobtrusive remote monitoring method for real-life cognitive functioning among persons with MS, which may improve the detection of relapses, evaluate treatment efficacy, and track disability progression.

The efficacy of speed of processing training for improving processing speed in individuals with multiple sclerosis: a randomized clinical trial.

OBJECTIVE: The current study examines the efficacy of speed of processing training (SOPT) to improve processing speed (PS) in individuals with multiple sclerosis (MS). Outcomes included changes in the useful field of view (UFOV) and neuropsychological evaluation (NPE). METHODS: This double-blind, placebo-controlled randomized clinical trial included 84 participants with clinically definite MS and impaired PS, 43 in the treatment group and 41 in the placebo control group. Participants completed a baseline NPE and a repeat NPE post-treatment. The treatment group was randomized to booster sessions or no contact. Long-term follow-up assessments were completed 6 months after treatment. RESULTS: A significant effect of SOPT was observed on both the UFOV (large effect) and pattern comparison with a similar pattern of results noted on letter comparison, albeit at a trend level. The treatment effect was maintained 6 months later. The impact of booster sessions was not significant. Correlations between degree of improvement on the UFOV and the number of levels completed within each training task were significant for both speed and divided attention indicating that completion of more levels of training correlated with greater benefit. CONCLUSION: SOPT is effective for treating PS deficits in MS with benefit documented on both the UFOV and a neuropsychological measure of PS. Less benefit was observed as the outcome measures became more distinct in cognitive demands from the treatment. Long-term maintenance was observed. The number of training levels completed within the 10-sessions exerted a significant impact on treatment benefit, with more levels completed resulting in greater benefit.

The adapted symbol digit modalities test: Examining the impact of response modality.

BACKGROUND: Information processing speed is often impaired in neurological disorders, as well as with healthy aging. Thus, being able to accurately assess information processing speed is of high importance. One of the most commonly used tests to examine information processing speed is the Symbol Digit Modalities Test (SDMT), which has been shown to have good psychometric properties. OBJECTIVES: The current study aims to examine differences between two response modalities, written and oral, on the performance of an adapted version of the Symbol Digit Modalities Test. METHODS: Ninety-nine individuals completed two alternate forms of the adapted version of the SDMT (aSDMT). Participants were instructed to complete the five lines of the task as quickly and accurately as possible. On one form participants were instructed to provide their response in writing and on the other one, orally. Form and response modality (oral vs. written) were counterbalanced to control for practice effects. RESULTS: On average, there was a significant difference between response modalities, such that participants needed more time to respond when the response modality was written. For both response modalities, time to complete each line of stimuli decreased as the task progressed. While changes in response time on the first four lines of stimuli on the oral version were not found, there was a substantial improvement in response time on the fifth line. In contrast, on the written version a gradual learning effect was observed, in which response time was the slowest on the first two lines, an intermediate response time was noted on line 3, and the fastest response time was achieved on lines four and five. CONCLUSION: The current study demonstrates that response modality, oral versus written, can significantly impact performance efficiency (the length of time it takes to complete a task), but not accuracy (total correct responses), on a new adaptation of the SDMT, the aSDMT.

Smell as a clinical-marker for functional limitations in multiple sclerosis: A pilot study.

BACKGROUND: Olfactory dysfunction is a common symptom of multiple sclerosis (MS). The questions of whether and to what degree olfactory dysfunction can serve as a clinical marker of MS disability (i.e. cognitive impairments and functional limitations) are not yet answered. The current study aimed to explore associations between olfactory function (i.e. smell identification) with cognitive capacities, functional performance and quality of life (QOL) in persons with MS. METHODS: Olfactory function was measured by the University of Pennsylvania Smell Identification Test (UPSIT). Functional ability was assessed by the Actual RealityTM (AR) task. QOL was assessed by the Multiple Sclerosis Quality of Life-54 (MSQOL-54). Cognition was assessed by the Brief International Cognitive Assessment for MS (BICAMS) in 23 MS patients and 15 matched healthy controls. RESULTS: MS patients had lower UPSIT scores than healthy controls. Worse UPSIT scores were associated with reduced performances on the BICAMS and AR task as well as lower MSQOL-54 scores. Specifically, UPSIT scores were related to MSQOL-54 scores independent of BICAMS composite scores, while the relationship between UPSIT score and AR performance was mediated by BICAMS composite score. CONCLUSION: This study confirms previous studies which concluded that olfactory function is impaired in MS. Furthermore, olfactory dysfunction is related to limitations in activity performance and QOL. Taken together with previous studies, olfactory function may be considered as a clinical marker related to MS disability. Longitudinal studies are needed to confirm these results.

Visual and motor confounds on the symbol digit modalities test.

BACKGROUND: Slowed information processing speed is the most prevalent cognitive symptom in persons with multiple sclerosis (MS). The most commonly used instrument to measure information processing speed in MS is the Symbol Digit Modalities Test (SDMT). However, visual, oculomotor, and oralmotor deficits are frequently observed in persons with MS, and performance on the SDMT relies on these visual and motor functions, in addition to cognition. METHODS: The current study examined the relationship between the SDMT and the King-Devick Test (KDT). The KDT encompasses similar oculomotor and oralmotor demands as the SDMT but requires a smaller attentional load. One hundred and thirty participants with MS completed the oral version of the SDMT and the KDT. Ordinary nonparametric bootstrapped regression models were performed with 1000 bootstrapped samples. Bootstrapped confidence intervals (CIs) were bias-corrected. RESULTS: KDT performance explained 31% (bootstrapped CI: 18 - 43%) of the variance of SDMT performance (moderate correlation), much more than demographic and disease-related variables (0.7% and 10%, respectively). CONCLUSIONS: Visual, oralmotor, and oculomotor functions contributed significantly to SDMT performance. Therefore, these sensory and motor functions must be taken into account when interpreting SDMT scores.

Comparing learning performance on the open trial selective reminding test with the California verbal learning test II in traumatic brain injury.

Introduction: Learning and memory deficits are prevalent following moderate to severe traumatic brain injury (TBI), affecting between 54% and 84% of impacted individuals.Objective: The current study examined learning performance on two tests of verbal memory: the OT-SRT and the CVLT-II.Methods: Sixty-eight participants with TBI performed the OT-SRT and the CVLT-II on two different days. Additionally, all participants completed cognitive tests assessing processing speed, working memory and executive functions. By definition, all participants with TBI were identified as having impaired learning on the OT-SRT, however only 38 were also identified as impaired on the CVLT-II. The sample was thus divided into two groups, those who failed both tests (Fail-2) and those who failed only the OT-SRT (Fail-1).Results: The Failed-1 group showed significantly better performance in processing speed, working memory and executive functions compared to the Fail-2 group. On the CVLT-II, the Fail-1 group performed significantly better on the number of words recalled on trials 1 and 5 compared to the Fail-2 group. Both groups performed similarly the OT-SRT.Discussion: The CVLT-II and the OT-SRT are not equivalent tests and should not be used interchangeably.

Comparing the Open Trial - Selective Reminding Test results with the California Learning Verbal Test II in multiple sclerosis.

We compared the California Learning Verbal Test II (CVLT II) and the Open Trial-Selective Reminding Test (OT-SRT) in assessing learning in persons with Multiple Sclerosis. One-hundred and twelve participants with multiple sclerosis performed the OT-SRT and the CVLT II on two different days. All participants completed additional cognitive tests assessing information processing speed (IPS), working memory (WM), and executive functions (EF). By definition, all participants were identified as having impaired learning on the OT-SRT (i.e., z score <-1.0); however, only 38 participants (33.9%) were identified as having impaired learning on the CVLT II (i.e., a z score <-1 total correct responses trials 1-5). The sample was thus divided into two groups, those who failed both tests (Fail-2) and those who failed only one (Fail-1). The Fail-2 group showed poorer performance on EF, WM and IPS in comparison with the Fail-1 group. On the CVLT II, the Fail-1 group showed a significantly greater improvement between trials 1 and 5, as compared with the Fail-2 group. However, the two groups performed similarly on the OT-SRT. Correlation analysis showed that EF is positively correlated with CVLT II learning slope but not with OT-SRT learning slope. The CVLT II and the OT-SRT are not equivalent tests: while the CVLT II appears to be sensitive to overall cognitive dysfunction, the OT-SRT is more sensitive to focal learning and memory impairments.

A Pilot Study Examining Speed of Processing Training (SPT) to Improve Processing Speed in Persons With Multiple Sclerosis.

Background: Individuals with Multiple Sclerosis (MS) have significant impairments in processing speed (PS) and such impairments may underlie other cognitive deficits common in MS and limit performance of everyday life activities. Objective: To examine the efficacy of a computerized PS intervention, Speed of Processing Training (SPT), in persons with MS on PS, memory and everyday activities. Methods: Twenty-one individuals with clinically definite MS and an objectively assessed impairment in PS were included in a controlled randomized clinical trial, randomly assigned to a treatment group or a control group. Participants were assessed prior to and within 1 week of completing the treatment. Outcome measures included traditional neuropsychological tests measuring PS and memory, and an assessment of PS in daily life activities. Results: The treatment group showed a significant improvement on neuropsychological tests of PS and new learning and memory. A significant improvement was additionally noted in the treatment group on measures of PS in everyday life. These changes were not observed in the control group. Conclusions: Results provide preliminary data in support of SPT in treating PS deficits in persons with MS. Additional research is needed with larger samples and more comprehensive outcome measures.

Role of Demographic and Clinical Factors in Cognitive Functioning of Persons with Relapsing-Remitting and Progressive Multiple Sclerosis.

BACKGROUND: Age and time post-diagnosis can significantly impact cognitive and motor functions in multiple sclerosis (MS); however, studies often fail to account for these factors when assessing differences between disease courses. OBJECTIVES: Examine differences between relapsing-remitting and progressive MS in cognition, motor function, and everyday activities, controlling for age, education, and time post-diagnosis. METHODS: Twenty-one persons with relapsing-remitting MS (RRMS group), 21 with progressive MS (PMS group), and 21 healthy participants (HCs), matched on age, education, and time post-diagnosis, completed tests of cognitive abilities, motor functions, and everyday functional activities. RESULTS: The two groups with MS did not differ on cognitive performance. Poorer performance in processing speed was noted in both MS groups in comparison with the HC group. Motor function was worse for the PMS group compared with the HC and RRMS groups. The RRMS group showed poorer upper limb functioning compared to the HC group. The PMS group had more difficulty with everyday activities as compared with both the RRMS and HC group. CONCLUSIONS: When comparing differences in functioning between MS disease courses, attention should be paid to the demographic characteristics of the samples. (JINS, 2018, 24, 139-146).

Information processing speed in multiple sclerosis: Past, present, and future.

BACKGROUND: Information processing speed (IPS) is a prevalent cognitive impairment in multiple sclerosis (MS). OBJECTIVES: This review aims to summarize the methods applied to assess IPS in MS and its theoretical conceptualization. A PubMed search was performed to select articles published between 1 January 2004 and 31 December 2013, resulting in 157 articles included. RESULTS: The majority (54%) of studies assessed IPS with heterogeneous samples (several disease courses). Studies often report controlling for presence of other neurological disorders (60.5%), age (58.6%), education (51.6%), alcohol history (47.8%), or use of steroids (39.5%). Potential confounding variables, such as recent relapses (50.3%), history of developmental disorders (19.1%), and visual problems (29.9%), were often neglected. Assessments used to study IPS were heterogeneous (ranging from simple to complex tasks) among the studies under review, with 62 different tasks used. Only 9.6% of articles defined the construct of IPS and 22.3% discussed IPS in relation to a theoretical model. FUTURE DIRECTIONS: The challenges for the upcoming decade include clarification of the definition of IPS as well as its theoretical conceptualization and a consensus on assessment. Based on the results obtained, we propose a new theoretical model, the tri-factor model of IPS.

Neuro-Ophthalmic Syndromes and Processing Speed in Multiple Sclerosis.

The impact of prior neuro-ophthalmic syndromes on the performance on vision-based neuropsychological tasks in patients with multiple sclerosis (MS) is unknown. Two groups of MS participants, one with (Msos+) and the other without (Msos-), a history of neuro-ophthalmic syndromes, underwent neuropsychological assessment and were compared with healthy age- and education-matched controls (HC). Participants with Msos+ performed significantly worse on the symbol digit modalities test than the Msos- (P < 0.03) and the HC groups (P < 0.01) and coding (P < 0.01). A clinical history of neuro-ophthalmic syndromes is associated with reduced performance on visual processing speed tasks.

Texture Analysis of Recurrence Plots Based on Wavelets and PSO for Laryngeal Pathologies Detection.

This paper deals with the discrimination between healthy and pathological speech signals using recurrence plots and wavelet transform with texture features. Approximation and detail coefficients are obtained from the recurrence plots using Haar wavelet transform, considering one decomposition level. The considered laryngeal pathologies are: paralysis, Reinke's edema and nodules. Accuracy rates above 86% were obtained by means of the employed method.