-
[show abstract]
[hide abstract]
ABSTRACT: Head movement during functional magnetic resonance imaging (fMRI) degrades data quality. The effects of small movements can be ameliorated during data postprocessing, but data associated with severe movement is frequently discarded. In discarding these data, it is often assumed that head-movement is a source of random error, and that data can be discarded from subjects with severe movement without biasing the sample. We tested this assumption by examining whether head movement was related to task difficulty and cognitive status among persons with multiple sclerosis (MS). Thirty-four persons with MS were scanned while performing a working memory task with three levels of difficulty (the N-back task). Maximum movement (angle, shift) was estimated for each difficulty level. Cognitive status was assessed by combining performance on a working memory and processing speed task. An interaction was found between task difficulty and cognitive status (high vs. low cognitive ability): there was a linear increase in movement as task difficulty increased that was larger among subjects with lower cognitive ability. Analyses of the signal-to-noise ratio (SNR) confirmed that increases in movement degraded data quality. Similar, though far smaller, effects were found in a cohort of healthy control (HC) subjects. Therefore, discarding data with severe movement artifact may bias MS samples such that only those with less-severe cognitive impairment are included in the analyses. However, even if such data are not discarded outright, subjects who move more (MS and HC) will contribute less to the group-level results because of degraded SNR. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
Human Brain Mapping 07/2012; · 5.88 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Background: Patients with multiple sclerosis (MS) suffer memory impairment but the link between MS-related neuroanatomical changes (brain atrophy) and memory is relatively weak.Objective: The purpose of this study was to use functional magnetic resonance imaging (fMRI) to investigate task-induced default network (DN) deactivation as a neurophysiologic biomarker of memory functioning in MS.Methods: Twenty-eight MS patients underwent high-resolution MRIs to measure brain atrophy (third ventricle width, cerebral gray matter, cerebral white matter, parenchymal fraction, and thalamic, caudate, hippocampal, and amygdala volumes), and fMRI blood oxygen level dependent (BOLD) signal to measure DN deactivation during sustained attention relative to rest. Neuropsychological assessment of episodic memory was performed on a separate day. We used hierarchical regression to predict memory, with age, education, and depression in step one, brain atrophy within step two, DN activity within step three, and the interaction between brain atrophy and DN activity in step four.Results: Brain atrophy predicted worse memory but DN activity independently predicted memory over-and-above measurements of brain atrophy (R(2)=0.108), with greater DN activity (lesser deactivation) linked to better memory. A significant brain atrophy by DN activity interaction indicated a stronger relationship between memory and DN activity among patients with more advanced disease, at which point higher DN activity protects patients from disease/atrophy-related memory impairment. To establish specificity, we showed no relationship between DN activity and non-memory cognition, and no relationship between non-DN brain activity and memory.Conclusion: Maintenance of DN activity during sustained attention was supported as a sensitive and specific neurophysiologic biomarker of episodic memory functioning in MS, even when controlling for neuroanatomical changes (brain atrophy).
Multiple Sclerosis 06/2012; · 4.26 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Patients with multiple sclerosis (MS) have more clinical exacerbations and T2 lesion activity during warmer weather. The current study is the first to investigate whether outdoor temperature is related to cognitive status across patients with MS (cross-sectional analysis), and whether cognitive status fluctuates with changes in outdoor temperature within patients with MS (longitudinal analysis).
For the cross-sectional analysis, 40 patients with MS and 40 healthy control (HC) subjects were recruited throughout the calendar year. Cognitive status (processing speed, memory) and outdoor temperature were recorded for the day of testing. We calculated partial correlations between cognitive status and temperature for patients with MS and HCs, controlling for demographic and disease variables. For the longitudinal analysis, cognitive status and outdoor temperature were recorded at baseline and 6-month follow-up in a separate sample of 45 patients with MS. We calculated the partial correlation between temperature and cognitive status at follow-up, controlling for baseline temperature and cognitive status (i.e., whether temperature changes are related to cognitive changes within patients with MS).
Cross-sectionally, warmer temperature was related to worse cognitive status in patients with MS (r(p) = -0.45, p = 0.006), not in HCs (r(p) = 0.00, p = 0.984). Longitudinally, increased outdoor temperature from baseline to follow-up was related to a decline in cognitive status within patients with MS (r(p) = -0.39, p = 0.010).
Cognitive status in patients with MS is worse on warmer days, consistent with a previously established link between heat and lesion activity. Our findings have implications for clinical trial planning, treatment, and lifestyle decisions. We discuss cognitive status as a potential marker of quiescent exacerbations.
Neurology 03/2012; 78(13):964-8. · 8.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Consistent with the cognitive reserve hypothesis, lifetime intellectual enrichment protects MS patients from cognitive impairment. As studies have focused predominately on patients with relapsing-remitting courses, it is unknown whether lifetime enrichment is protective against cognitive impairment in patients with secondary-progressive MS (SPMS), a more advanced disease course.
Examine whether greater lifetime intellectual enrichment moderates/reduces the deleterious effect of SPMS on memory and cognitive efficiency.
Twenty-five SPMS patients and 25 healthy controls (HC) completed neuropsychological tasks, yielding two composite scores: memory and cognitive efficiency. An estimate of lifetime enrichment was created from educational attainment and vocabulary knowledge. Regression analyses predicted memory and cognitive efficiency, with age, sex, intellectual enrichment and group (SPMS, HC) controlled in step one, and the interaction between intellectual enrichment and group evaluated within step two.
Interactions emerged between intellectual enrichment and group when predicting memory (R (2)Δ=0.081, p = 0.041) and cognitive efficiency (R (2)Δ=0.064, p = 0.024), such that SPMS patients exhibited deficits relative to HCs at lower levels of enrichment, but these SPMS-related cognitive deficits were absent at higher levels of enrichment.
Intellectual enrichment protects SPMS patients from cognitive impairment, thereby extending the cognitive reserve hypothesis to this more advanced MS disease course.
Multiple Sclerosis 03/2012; 18(10):1454-8. · 4.26 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Generally, so-called control processes are thought to be necessary when we must perform one out of several competing actions. Some examples include performance of a less well-practiced action instead of a well-practiced one (prepotency); learning a new action (novelty); and rapidly switching from one action to another (task-switching). While it certainly is difficult to perform the desired action in these circumstances, it is less clear that a separate set of processes (e.g., control processes) are necessary to explain the observed behavior. Another way to approach the study of control processes is to investigate physiological dependent measures (e.g., electrophysiological or neuroimaging measures). Although these offer another avenue of inquiry into control processes, they have yet to furnish unambiguous evidence that control processes exist. While this might suggest that there are no control processes, it is also possible that our methods are insufficiently sensitive to measure control processes. We have investigated this latter possibility using tasks that are neuroanatomically distinct, though within the same modality (vision). This approach did not yield evidence for a separable set of control processes. However, recent works using a task-switching paradigm in which subjects switch between a visual and an auditory task suggest that switching both task and modality may be importantly different than switching task within a given modality. This may represent a way forward in the study of control processes.
Psychological Research 06/2011; 75(6):535-43. · 2.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Memory impairment is prevalent in multiple sclerosis (MS), but no drugs are approved to treat these memory problems.
The objective of the study was to examine the effect of l-amphetamine versus placebo on auditory/verbal memory and visual/spatial memory in MS patients with and without baseline memory impairment.
We conducted a re-analysis of a previously published clinical trial in which MS patients were randomly assigned to treatment (30 mg l-amphetamine, N = 99) or placebo (N = 37) in a four-week, double-blind, parallel-group, dose titration trial. Auditory/verbal memory (CVLT-II: Long Delay Free Recall) and visual/spatial memory (BVMT-R: Delayed Recall) were assessed at baseline and follow-up across subgroups of patients with intact baseline memory (mean = 50th percentile) or impaired baseline memory (mean = 2nd percentile). Primary analyses: 2 (l-amphetamine, placebo) × 2 (baseline, follow-up), × 2 (baseline memory intact, baseline memory impaired) ANOVAs performed separately for auditory/verbal and visual/spatial memory.
For both auditory/verbal and visual/spatial memory, we observed significant 2 × 2 × 2 interactions whereby l-amphetamine improved memory more than placebo, and this effect was specific to patients with baseline memory impairment.
Among memory-impaired patients, memory improved about 48.5% for those on l-amphetamine, but only 1.0% on placebo. Treatment with l-amphetamine produced large memory gains among memory-impaired MS patients.
Multiple Sclerosis 05/2011; 17(9):1141-5. · 4.26 Impact Factor
-
Neurology 03/2011; 76(9):847; author reply 847-8. · 8.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Subjective reports of memory functioning are often included as part of neuropsychological evaluations. However, information from subjective measures often conflicts with formal testing results. The current study explored the relationships among self-reported memory functioning and objective learning and memory measures. Sixty-four multiple sclerosis (MS) patients completed a self-report memory questionnaire (Memory Functioning Questionnaire, MFQ) and objective measures of learning and memory (California Verbal Learning Test-II, CVLT-II; Open-Trial Selective Reminding Test, OT-SRT; and Prose Memory, PM). Significant positive correlations were found between self-reported memory functioning and recall following initial exposure to material: OT-SRT Trial 1 (r = .42; p = .001); CVLT-II Trial 1 (r = .39; p = .002): PM Immediate Recall (r = .28; p = .028). Subjective memory was unrelated to recall performance on subsequent learning trials, aggregate learning scores, or delayed free recall. Results suggest that self-reported memory functioning in MS patients may be specifically related to single-trial learning. (JINS, 2011, 17, 1-5).
Journal of the International Neuropsychological Society 03/2011; · 2.76 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Memory impairment is common following traumatic brain injury (TBI), but interventions to improve memory in persons with TBI have been ineffective. Retrieval practice is a robust memory strategy among healthy undergraduates, whereby practice retrieving information shortly after it is presented leads to better delayed recall than simple restudy. In a verbal paired associate paradigm, we investigated the effect of retrieval practice relative to massed and spaced restudy on delayed recall in 14 persons with chronic memory impairment following a TBI and 14 age-matched healthy controls. A significant learning condition (massed restudy, spaced restudy, retrieval practice) by group (TBI, healthy) interaction emerged, whereby only healthy controls benefited from spaced restudy (i.e., distributed learning) over massed restudy, but both groups greatly benefited from retrieval practice over massed and spaced restudy. That is, retrieval practice greatly improves memory in persons with TBI, even when other mnemonic strategies (e.g., distributed learning) are less effective.
Journal of the International Neuropsychological Society 10/2010; 16(6):1147-50. · 2.76 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Learning and memory impairments are prevalent among persons with multiple sclerosis (MS); however, such deficits are only weakly associated with MS disease severity (brain atrophy). The cognitive reserve hypothesis states that greater lifetime intellectual enrichment lessens the negative impact of brain disease on cognition, thereby helping to explain the incomplete relationship between brain disease and cognitive status in neurologic populations. The literature on cognitive reserve has focused mainly on Alzheimer disease. The current research examines whether greater intellectual enrichment lessens the negative effect of brain atrophy on learning and memory in patients with MS.
Forty-four persons with MS completed neuropsychological measures of verbal learning and memory, and a vocabulary-based estimate of lifetime intellectual enrichment. Brain atrophy was estimated with third ventricle width measured from 3-T magnetization-prepared rapid gradient echo MRIs. Hierarchical regression was used to predict learning and memory with brain atrophy, intellectual enrichment, and the interaction between brain atrophy and intellectual enrichment.
Brain atrophy predicted worse learning and memory, and intellectual enrichment predicted better learning; however, these effects were moderated by interactions between brain atrophy and intellectual enrichment. Specifically, higher intellectual enrichment lessened the negative impact of brain atrophy on both learning and memory.
These findings help to explain the incomplete relationship between multiple sclerosis disease severity and cognition, as the effect of disease on cognition is attenuated among patients with higher intellectual enrichment. As such, intellectual enrichment is supported as a protective factor against disease-related cognitive impairment in persons with multiple sclerosis.
Neurology 06/2010; 74(24):1942-5. · 8.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The testing effect is a robust cognitive phenomenon by which memory retrieval on a test improves subsequent recall more than restudying. Also known as retrieval practice, the testing effect has been studied almost exclusively in healthy undergraduates. The current study investigated whether retrieval practice during testing leads to better delayed recall than restudy among persons with multiple sclerosis (MS), a neurologic disease associated with memory dysfunction. In a within-subjects design, 32 persons with MS and 16 demographically matched healthy controls (HC) studied 48 verbal paired associates (VPA) divided across 3 learning conditions: massed restudy (MR), spaced restudy (SR), and spaced testing (ST). Delayed VPA cued recall was measured after 45 min. There was a large main effect of learning condition (etap2 = .54, p < .001) such that both MS and HC participants produced better delayed recall for VPAs learned through ST relative to MR and SR; and SR relative to MR. This same pattern was observed for MS participants with objective memory impairment (n = 16), thereby providing the first evidence that retrieval practice improves memory more than restudy among persons with neurologically based memory impairment.
Neuropsychology 03/2010; 24(2):267-72. · 3.82 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The cognitive reserve hypothesis helps to explain the incomplete relationship between brain disease and cognitive status in people with neurologic diseases, including Alzheimer's; disease and multiple sclerosis. Lifetime intellectual enrichment (estimated with education or vocabulary knowledge) lessens the negative impact of brain disease on cognition, such that people with greater enrichment are able to withstand more severe neuropathology before suffering cognitive impairment or dementia. The current research is the first to investigate directly the relationship between intellectual enrichment and an index of cerebral activity (the blood oxygen level dependent signal) in a neurologic sample. Multiple sclerosis patients completed a vocabulary-based estimate of lifetime intellectual enrichment. Disease severity was estimated with brain atrophy. Cognitive status was measured with the Symbol Digit Modalities Test. Cerebral activity (functional magnetic resonance imaging blood oxygen level dependent signal) and behavioural performance (accuracy, reaction time) were recorded during the visual N-Back working memory task (three levels of demand: 0-, 1-, 2-Back). All patients produced perfect/nearly perfect accuracy during lower demands (0- and 1-Back), and reaction time was unrelated to intellectual enrichment; however, voxelwise partial correlations controlling for brain atrophy revealed strong positive correlations between intellectual enrichment and cerebral activity within the brain's; default network (e.g. anterior and posterior cingulate corticies), indicating that patients with greater enrichment were able to maintain resting state activity during cognitive processing better. In turn, intellectual enrichment was negatively associated with prefrontal recruitment, suggesting that patients with lesser enrichment required more cerebral resources to perform the same cognitive task as patients with greater enrichment. This same pattern of enrichment-related cerebral activity was observed when cognitive demands increased (2-Back), and intellectual enrichment was negatively associated with reaction time. Principle components analysis revealed a single cognitive reserve network across tasks (greater default network, lesser prefrontal recruitment). Expression of this network almost fully mediated the positive relationship between intellectual enrichment and cognitive status (Symbol Digit Modalities Test). Also, expression of this network was positively associated with brain atrophy when controlling for cognitive status, indicating that patients with greater expression of this network can withstand more severe brain disease before exhibiting cognition similar to patients with lesser network expression. Of note, similar functional magnetic resonance imaging research with healthy adults has not found an association between intelligence and cerebral efficiency. The unique relationship between intellectual enrichment and cerebral efficiency in neurologic patients is consistent with the cognitive reserve hypothesis, which does not posit that enrichment leads to gains in neurocognitive functioning per se; rather, enrichment protects against neurocognitive decline secondarily to disease.
Brain 12/2009; 133(Pt 2):362-74. · 9.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: According to the cognitive reserve hypothesis, neuropsychological expression of brain disease is attenuated among persons with higher education or premorbid intelligence. The current research examined cognitive reserve in multiple sclerosis (MS) by investigating whether the negative effect of brain atrophy on information processing (IP) efficiency is moderated by premorbid intelligence. Thirty-eight persons with clinically definite MS completed a vocabulary-based estimate of premorbid intelligence (Wechsler Vocabulary) and a composite measure of IP efficiency (Symbol Digit Modalities Test and Paced Auditory Serial Addition Task). Brain atrophy was estimated from measurements of third ventricle width using high-resolution anatomical brain magnetic resonance imaging (magnetization-prepared rapid gradient echo). In a hierarchical regression analysis controlling for age and depressive symptomatology, brain atrophy predicted worse IP efficiency (R2 = .23, p = .003) and cognitive reserve predicted better IP efficiency (R2 = .13, p = .013), but these effects were moderated by an Atrophy x Cognitive Reserve interaction (R2 = .15, p = .004). The negative effect of brain atrophy on IP efficiency was attenuated at higher levels of reserve, such that MS subjects with higher reserve were better able to withstand MS neuropathology without suffering cognitive impairment. Results help explain the incomplete and inconsistent relationship between brain atrophy and IP efficiency in previous research.
Journal of the International Neuropsychological Society 08/2009; 15(4):606-12. · 2.76 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Multiple Sclerosis (MS) is a disease of the central nervous system affecting millions of people worldwide. In addition to the disabling physical symptoms of MS, roughly 65% of individuals with MS also experience significant cognitive dysfunction, especially in the domains of learning/memory, processing speed (PS) and working memory (WM). The purpose of this review is to examine major topics in research on cognitive dysfunction, as well as review recent functional magnetic resonance imaging (fMRI) studies focusing on cognitive dysfunction in MS. Additionally, directions for future research are discussed.
Frontiers in Bioscience 02/2009; 14:1730-44. · 3.52 Impact Factor
