Neocortical Atrophy, Third Ventricular Width, and Cognitive Dysfunction in Multiple Sclerosis

Benedict, Ralph H. B.; Bruce, Jared M.; Dwyer, Michael G.; Abdelrahman, Nadir; Hussein, Sarah; Weinstock‐Guttman, Bianca; Garg, Neeta; Munschauer, Frederick E.; Zivadinov, Robert

doi:10.1001/archneur.63.9.1301

Cited by 282 publications

(274 citation statements)

References 32 publications

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“…The association between a widespread thinner cortex and an increased number of skipped beats is in line with previous studies emphasizing the relationship between volume/thickness of the neocortex and mental processing efficiency in MS (Amato et al, 2007;Benedict et al, 2006). We propose that the number of skipped beats reflect speed and attention (and arguably experienced task difficulty), both in MS patients and healthy controls.…”

Section: Discussionsupporting

confidence: 91%

“…Similar to many other studies on cognition in MS (e.g. Benedict et al, 2006), we expect a wider third ventricle to be associated with poorer behavioral performance. Cortical thickness evaluation was performed by means of Freesurfer image analysis suite, which is documented and freely available online (http://surfer.nmr.mgh.harvard.edu).…”

Section: Mri Data Acquisition Post-processing and Hypothesessupporting

confidence: 87%

“…Demyelinated T2 lesions in the white matter -the pathological hallmark of MSare only modestly correlated with cognitive impairment (Lazeron et al, 2005;Rao, Leo, Haughton, St Aubin-Faubert, & Bernardin, 1989). Higher correlations are observed between cognitive performance and third ventricle width, which is traditionally considered the best single MRI predictor for MS-related cognitive impairment (Benedict et al, 2004(Benedict et al, , 2006. More recent research highlights cortical pathology as one of the major substrates of cognitive decline in MS (for a review see Messina & Patti, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…voxel-based lesion symptom mapping (VLSM). Central brain atrophy was examined by measuring the width of the third ventricle, implemented according to the procedure defined by Benedict and colleagues (Benedict et al, 2006). Similar to many other studies on cognition in MS (e.g.…”

Section: Mri Data Acquisition Post-processing and Hypothesesmentioning

confidence: 99%

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Random number generation deficits in patients with multiple sclerosis: Characteristics and neural correlates

Geisseler

Pflugshaupt

Buchmann

et al. 2016

Cortex

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Human subjects typically deviate systematically from randomness when attempting to produce a sequence of random numbers. Despite an increasing number of behavioral and functional neuroimaging studies on random number generation (RNG), its structural correlates have never been investigated. We set out to fill this gap in 44 patients with multiple sclerosis (MS), a disease whose impact on RNG has never been studied. The RNG task required the paced (1 Hz) generation of the numbers from 1 to 6 in a sequence as random as possible. The same task was administered in 39 matched healthy controls. To assess neuroanatomical correlates such as cortical thickness, lesion load and third ventricle width, all subjects underwent high-resolution structural MRI. Compared to controls, MS patients exhibited an enhanced tendency to arrange consecutive numbers in an ascending order ("forward counting"). Furthermore, patients showed a higher susceptibility to rule breaks (producing out-of-category digits like 7) and to skip beats of the metronome. Clinico-anatomical correlation analyses revealed two main findings: First, increased counting in MS patients was associated with higher cortical lesion load. Second, increased number of skipped beats was related to widespread cortical thinning. In conclusion, our test results illustrate a loss of behavioral complexity in the course of MS, while the imaging results suggest an association between this loss and cortical pathology. AbstractHuman subjects typically deviate systematically from randomness when attempting to produce a sequence of random numbers. Despite an increasing number of behavioral and functional neuroimaging studies on random number generation (RNG), its structural correlates have never been investigated. We set out to fill this gap in 44 patients with multiple sclerosis (MS), a disease whose impact on RNG has never been studied. The RNG task required the paced (1 Hz) generation of the numbers from 1 to 6 in a sequence as random as possible. The same task was administered in 39 matched healthy controls. To assess neuroanatomical correlates such as cortical thickness, lesion load and third ventricle width, all subjects underwent high-resolution structural MRI. Compared to controls, MS patients exhibited an enhanced tendency to arrange consecutive numbers in an ascending order ("forward counting"). Furthermore, patients showed a higher susceptibility to rule breaks (producing out-of-category digits like 7) and to skip beats of the metronome. Clinicoanatomical correlation analyses revealed two main findings: First, increased counting in MS patients was associated with higher cortical lesion load. Second, increased number of skipped beats was related to widespread cortical thinning. In conclusion, our test results illustrate a loss of behavioral complexity in the course of multiple sclerosis, while the imaging results suggest an association between this loss and cortical pathology. KeywordsRandom number generation; mental dice task; multiple sclerosis, neural correlates

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Section: Discussionsupporting

confidence: 91%

Section: Mri Data Acquisition Post-processing and Hypothesessupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Mri Data Acquisition Post-processing and Hypothesesmentioning

confidence: 99%

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Random number generation deficits in patients with multiple sclerosis: Characteristics and neural correlates

Geisseler

Pflugshaupt

Buchmann

et al. 2016

Cortex

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“…Similar to dysarthria, cognitive deficits are a common and prominent feature of MS. Research suggests that approximately 50% of MS patients are impaired on NP testing (Amato et al, 2006;Arnett, 2003;Benedict et al, 2006;Brass et al, 2006;Brassington & Marsh, 1998;Jonsson et al, 2006;Rao et al, 1991). As noted earlier, many of the tasks that are most sensitive to cognitive dysfunction in MS require the patient to make a rapid oral motor response.…”

Section: Introductionmentioning

confidence: 98%

Oralmotor slowing in multiple sclerosis: Relationship to neuropsychological tasks requiring an oral response

Arnett

Smith

Barwick

et al. 2008

J Inter Neuropsych Soc

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Although most neuropsychological batteries used with multiple sclerosis (MS) patients now exclude tests that require significant motor writing or manual manipulation speed, many of the most sensitive commonly used cognitive tests nonetheless require some type of rapid oral motor response. The aim of this study is to examine the extent to which primary oral motor articulation speed problems of individuals with MS contribute to performance and group differences on neuropsychological tasks requiring a rapid spoken response. Fifty MS patients and 50 healthy controls were administered the PASAT, COWAT, Animal Naming, and SDMT tests, in addition to a measure of rudimentary oral motor speed known as the maximum repetition rate of syllables and multisyllabic combinations (MRR) task. Regression analyses revealed that the amount of variance accounted for by the group (MS-Control) variable was reduced the following amounts for the tasks when the MRR was entered before the group variable: SDMT, 10% to 6%; PASAT, 4% to 2%; COWAT, 5% to 2%; Animal Naming, 11% to 7%. Our data suggest that rudimentary oral motor speed is slowed in MS patients and makes an important contribution to group differences in performance on commonly used neuropsychological tasks requiring a rapid spoken response. (JINS, 2008, 14, 454-462.)

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Association of Neocortical Volume Changes With Cognitive Deterioration in Relapsing-Remitting Multiple Sclerosis

Amato¹,

Portaccio²,

Goretti³

et al. 2007

Arch Neurol

207

151

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Background : We previously reported selective decreases of neocortical volumes in patients with early relapsing-remitting (RR) multiple sclerosis (MS) with mild cognitive impairment, with a good correlation between cortical volumes and cognitive measures.Objective: To assess the relevance of gray matter changes over time to changes in cognition in RRMS.Design: A longitudinal survey after 2.5 years. Each patient underwent a magnetic resonance imaging (MRI) protocol identical to that performed at baseline; cognitive performance was reassessed with the Rao Brief Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis. Setting: Two university MS clinics.Patients: Of 41 patients with RRMS who participated in the original cross-sectional study, 28 were available for the follow-up evaluation (18 women; mean±SD age, 37.1±8.9 years; mean±SD MS duration, 7.3±2.9 years; mean±SD Expanded Disability Status Scale score, 1.8±1.5). Main Outcome Measures:We measured the percentage of brain volume changes, normalized cortical volume (NCV) changes, and normalized deep gray matter volume changes on conventional T1-weighted MRIs and changes in lesion load on T2-weighted MRIs. The number of tests failed on the Rao Brief Repeatable Battery were used to classify the patients as cognitively deteriorating or stable or improving.Results: We identified 12 of 28 cognitively deteriorating and 16 of 28 stable or improving patients. These subgroups did not differ in the mean±SD percentage of brain volume changes (−2.1%±1.2% vs −1.3%±1.3%; P=.11), normalized deep gray matter volume changes (−2.1±2.8 mL vs −0.6±3.1 mL; P=.60), and changes in lesion load on T2-weighted MRIs (1.9±2.6 mL vs 1.6±2.3 mL; P=.73). However, NCV changes were significantly higher in deteriorating than in stable or improving patients (−43.0±18.9 mL vs −17.8 ± 26.6 mL; P = .007). In deteriorating patients, NCV changes were correlated with performance in a verbal fluency test (r=0.73; PϽ.001). In a regression model, only NCV changes were significantly associated with deteriorating cognitive performance (odds ratio, 0.8; 95% confidence interval, 0.7-0.9). Conclusion:Progressive neocortical gray matter loss is relevant to MS-associated cognitive impairment and may represent a sensitive marker of deteriorating cognitive performance in RRMS.

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Neocortical Atrophy, Third Ventricular Width, and Cognitive Dysfunction in Multiple Sclerosis

Cited by 282 publications

References 32 publications

Random number generation deficits in patients with multiple sclerosis: Characteristics and neural correlates

Random number generation deficits in patients with multiple sclerosis: Characteristics and neural correlates

Oralmotor slowing in multiple sclerosis: Relationship to neuropsychological tasks requiring an oral response

Association of Neocortical Volume Changes With Cognitive Deterioration in Relapsing-Remitting Multiple Sclerosis

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