Memory impairment in multiple sclerosis: Relevance of hippocampal activation and hippocampal connectivity

Background: Memory impairment is frequent in multiple sclerosis (MS), but it is unclear what functional brain changes underlie this cognitive deterioration. Objective: To investigate functional hippocampal activation and connectivity, in relation to memory performance in MS. Methods: Structural and functional magnetic resonance imaging data were acquired for 57 MS patients and 28 healthy controls (HCs), yielding hippocampal measures of volume, lesions, functional activation during a memory task and functional connectivity at rest. Memory function was based on two subtests of a larger neuropsychological test battery and related to hippocampal neuroimaging measures, using linear regression. Results: Hippocampal volume was lower in MS patients, as compared to HCs. In MS, hippocampal activation during the task was increased in cognitively preserved, but decreased in cognitively impaired, patients. Increased hippocampal connectivity was detected in MS patients, as compared to HCs, between the left hippocampus and the right posterior cingulate. Memory impairment in MS was explained (adjusted R2 = 0.27) by male gender, decreased hippocampal activation and increased hippocampal connectivity ( p = 0.001). Conclusions: Decreased activation of the hippocampus, increased connectivity and male gender were associated with worse memory performance in MS. These results indicate that increased activation and increased connectivity do not always coincide, and relate differently to cognitive dysfunction in MS.

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Hippocampal atrophy in relapsing-remitting and primary progressive MS: a comparative study

Multiple Sclerosis Journal ◽

10.1177/1352458510374893 ◽

2010 ◽

Vol 16 (9) ◽

pp. 1083-1090 ◽

Cited By ~ 35

Author(s):

VM Anderson ◽

LK Fisniku ◽

Z. Khaleeli ◽

MM Summers ◽

SA Penny ◽

...

Keyword(s):

Memory Performance ◽

Memory Function ◽

Hippocampal Volume ◽

Hippocampal Atrophy ◽

Primary Progressive ◽

Recall Memory ◽

Relapsing Remitting ◽

The Mean ◽

The Right ◽

With Memory

Background: In multiple sclerosis (MS), demyelination and neuroaxonal damage are seen in the hippocampus, and MRI has revealed hippocampal atrophy. Objectives: To investigate and compare hippocampal volume loss in patients with relapsing—remitting MS (RRMS) and primary progressive MS (PPMS) using manual volumetry, and explore its association with memory dysfunction. Methods: Hippocampi were manually delineated on volumetric MRI of 34 patients with RRMS, 23 patients with PPMS and 18 controls. Patients underwent neuropsychological tests of verbal and visuospatial recall memory. Linear regression was used to compare hippocampal volumes between subject groups, and to assess the association with memory function. Results: Hippocampal volumes were smaller in MS patients compared with controls, and were similar in patients with RRMS and PPMS. The mean decrease in hippocampal volume in MS patients was 317 mm3 (9.4%; 95% CI 86 to 549; p = 0.008) on the right and 284 mm3 (8.9%; 95% CI 61 to 508; p = 0.013) on the left. A borderline association of hippocampal volume with memory performance was observed only in patients with PPMS. Conclusion: Hippocampal atrophy occurs in patients with RRMS and PPMS. Factors additional to hippocampal atrophy may impact on memory performance.

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Default Network Connectivity Is Linked to Memory Status in Multiple Sclerosis

Journal of the International Neuropsychological Society ◽

10.1017/s1355617714000800 ◽

2014 ◽

Vol 20 (9) ◽

pp. 937-944 ◽

Cited By ~ 10

Author(s):

Victoria M. Leavitt ◽

Jessica Paxton ◽

James F. Sumowski

Keyword(s):

Multiple Sclerosis ◽

Memory Impairment ◽

Memory Performance ◽

Memory Function ◽

Network Connectivity ◽

Cognitive Status ◽

Default Network ◽

Resting State Functional Connectivity ◽

Cognitive Efficiency ◽

Straightforward Method

AbstractMemory impairment affects 50% of multiple sclerosis (MS) patients. Altered resting-state functional connectivity (FC) has been observed in the default network (DN) of MS patients. No study to date has examined the association of DN FC to its behavioral concomitant, memory. The approach of the present study represents a methodological shift allowing straightforward interpretation of FC alterations in MS, as it presupposes specificity of a network to its paired cognitive function. We examined FC from fMRI collected during rest in the DN of 43 MS patients with and without memory-impairment. Memory-intact patients showed increased DN FC relative to memory-impaired patients. There were no regions of higher FC in memory-impaired patients. DN FC was positively correlated with memory function, such that higher FC was associated with better memory performance. Results were unchanged after controlling for cognitive efficiency, supporting specificity of the DN to memory and not cognitive status more generally. These findings support DN FC as a marker of memory function in MS patients that can be targeted by future treatment interventions. Pairing a functional network with its behavioral concomitant represents a straightforward method for interpreting FC alterations in patients with MS. (JINS, 2014, 20, 1–8)

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The role of the thalamus and hippocampus in episodic memory performance in patients with multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458518760716 ◽

2018 ◽

Vol 25 (4) ◽

pp. 574-584 ◽

Cited By ~ 7

Author(s):

Katherine A Koenig ◽

Stephen M Rao ◽

Mark J Lowe ◽

Jian Lin ◽

Ken E Sakaie ◽

...

Keyword(s):

Multiple Sclerosis ◽

Episodic Memory ◽

Recall Performance ◽

Memory Performance ◽

Memory Function ◽

Memory Task ◽

Memory Loss ◽

Lesion Load ◽

Visual Spatial ◽

Volumetric Measures

Background: Episodic memory loss is one of the most common cognitive symptoms in patients with multiple sclerosis (MS), but the pathophysiology of this symptom remains unclear. Both the hippocampus and thalamus have been implicated in episodic memory and show regional atrophy in patients with MS. Objective: In this work, we used functional magnetic resonance imaging (fMRI) during a verbal episodic memory task, lesion load, and volumetric measures of the hippocampus and thalamus to assess the relative contributions to verbal and visual–spatial episodic memory. Methods: Functional activation, lesion load, and volumetric measures from 32 patients with MS and 16 healthy controls were used in a predictive analysis of episodic memory function. Results: After adjusting for disease duration, immediate recall performance on a visual–spatial episodic memory task was significantly predicted by hippocampal volume ( p < 0.003). Delayed recall on the same task was significantly predicted by volume of the left thalamus ( p < 0.003). For both memory measures, functional activation of the thalamus during encoding was more predictive than that of volume measures ( p < 0.002). Conclusion: Our results suggest that functional activation may be useful as a predictive measure of episodic memory loss in patients with MS.

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Effects of amnesia on processing in the hippocampus and default mode network during a naturalistic memory task: a case study

10.31234/osf.io/e9n8c ◽

2018 ◽

Author(s):

Christiane Oedekoven ◽

James L. Keidel ◽

Stuart Anderson ◽

Angus Nisbet ◽

Chris Bird

Keyword(s):

Functional Connectivity ◽

Episodic Memory ◽

Memory Performance ◽

Memory Task ◽

Structural Mri ◽

Brain Regions ◽

Left Hippocampus ◽

Cortical Regions ◽

The Right ◽

Encoding And Retrieval

Despite their severely impaired episodic memory, individuals with amnesia are able to comprehend ongoing events. Online representations of a current event are thought to be supported by a network of regions centred on the posterior midline cortex (PMC). By contrast, episodic memory is widely believed to be supported by interactions between the hippocampus and these cortical regions. In this MRI study, we investigated the encoding and retrieval of lifelike events (video clips) in a patient with severe amnesia likely resulting from a stroke to the right thalamus, and a group of 20 age-matched controls. Structural MRI revealed grey matter reductions in left hippocampus and left thalamus in comparison to controls. We first characterised the regions activated in the controls while they watched and retrieved the videos. There were no differences in activation between the patient and controls in any of the regions. We then identified a widespread network of brain regions, including the hippocampus, that were functionally connected with the PMC in controls. However, in the patient there was a specific reduction in functional connectivity between the PMC and a region of left hippocampus when both watching and attempting to retrieve the videos. A follow up analysis revealed that in controls the functional connectivity between these regions when watching the videos was correlated with memory performance. Taken together, these findings support the view that the interactions between the PMC and the hippocampus enable the encoding and retrieval of multimodal representations of the contents of an event.

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Hippocampal volume and subjective memory impairment in depressed patients

European Psychiatry ◽

10.1016/j.eurpsy.2004.05.003 ◽

2004 ◽

Vol 19 (7) ◽

pp. 438-440 ◽

Cited By ~ 20

Author(s):

Armin von Gunten ◽

Maria A. Ron

Keyword(s):

Memory Impairment ◽

Hippocampal Volume ◽

Subjective Memory ◽

Subjective Memory Impairment ◽

Depressed Patients ◽

The Right ◽

The Relationship

AbstractThe relationship between severity of subjective memory impairment and volume of the hippocampus/amygdala complex was investigated in non-demented depressed patients and it was found to correlate with decreasing volume in the right hippocampus.

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A single dose of cocaine enhances prospective memory performance

Journal of Psychopharmacology ◽

10.1177/0269881118783299 ◽

2018 ◽

Vol 32 (8) ◽

pp. 883-892

Author(s):

Nadia RPW Hutten ◽

Kim PC Kuypers ◽

Janelle HP van Wel ◽

Eef L Theunissen ◽

Stefan W Toennes ◽

...

Keyword(s):

Prospective Memory ◽

Drug Users ◽

Memory Performance ◽

Memory Task ◽

Acute Effect ◽

Drug Induced ◽

Attention Task ◽

The Right ◽

Induced Changes ◽

Prospective Memory Performance

Background: Prospective memory is the ability to recall intended actions or events at the right time or in the right context. While cannabis is known to impair prospective memory, the acute effect of cocaine is unknown. In addition, it is not clear whether changes in prospective memory represent specific alterations in memory processing or result from more general effects on cognition that spread across multiple domains such as arousal and attention. Aims: The main objective of the study was, therefore, to determine whether drug-induced changes in prospective memory are memory specific or associated with more general drug-induced changes in attention and arousal. Methods: A placebo-controlled, three-way, cross-over study including 15 regular poly-drug users was set up to test the influence of oral cocaine (300 mg) and vaporised cannabis (300+150 ‘booster’ µg/kg bodyweight) on an event-based prospective memory task. Attentional performance was assessed using a divided attention task and subjective arousal was assessed with the Profile of Mood States questionnaire. Results: Results showed that cocaine enhanced prospective memory, attention and arousal. Mean performance of prospective memory and attention, as well as levels of arousal were lowest during treatment with cannabis as compared with placebo and cocaine as evinced by a significantly increased trend across treatment conditions. Prospective memory performance was only weakly positively associated to measures of attention and arousal. Conclusion: Together, these results indicate that cocaine enhancement of prospective memory performance cannot be fully explained by parallel changes in arousal and attention levels, and is likely to represent a direct change in the neural network underlying prospective memory.

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Hippocampal volume is more related to patient-reported memory than objective memory performance in early multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458520922830 ◽

2020 ◽

pp. 135245852092283

Author(s):

Lisa Glukhovsky ◽

Rachel Brandstadter ◽

Victoria M Leavitt ◽

Stephen Krieger ◽

Korhan Buyukturkoglu ◽

...

Keyword(s):

Multiple Sclerosis ◽

Memory Performance ◽

Hippocampal Volume ◽

Magnetic Resonance Images ◽

Longitudinal Assessment ◽

Subjective Memory ◽

Cross Sectional ◽

Memory Decline ◽

Patient Reported ◽

Partial Correlations

Background: When persons with multiple sclerosis (MS) report memory decline but objective memory performance is normal, there is a bias toward believing objective test results. Objective: Investigate whether subjective memory decline or objective memory performance is more related to hippocampal and hippocampal subfield volumes in early MS. Methods: Persons with early MS ( n = 185; ⩽5.0 years diagnosed) completed a subjective memory questionnaire; an objective memory composite was derived from four memory tests. Total hippocampal and subfield volumes were derived from high-resolution 3.0 T magnetic resonance images (MRIs). Partial correlations assessed links between hippocampal volumes and both subjective and objective memory, controlling for age, sex, mood, and pre-morbid intelligence quotient (IQ). Results: Lower total hippocampal and CA1 volumes were related to worse subjective memory but not objective memory (controlling for multiple comparisons). Correlations between subjective memory and both CA1 and subiculum were significantly stronger than were correlations between objective memory and these subfields. Patients in the worst tertile of subjective memory complaints (but not objective memory) had lower hippocampal volumes than 35 demographically similar healthy controls. Conclusion: Patient-report is inherently a longitudinal assessment of within-person memory change in everyday life, which may be more sensitive to subtle disease-related changes than cross-sectional objective tests. Findings align with the aging literature.

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The presubiculum links incipient amyloid and tau pathology to memory function in older persons

Neurology ◽

10.1212/wnl.0000000000009362 ◽

2020 ◽

Vol 94 (18) ◽

pp. e1916-e1928

Author(s):

Heidi I.L. Jacobs ◽

Jean C. Augustinack ◽

Aaron P. Schultz ◽

Bernard J. Hanseeuw ◽

Joseph Locascio ◽

...

Keyword(s):

Memory Performance ◽

Memory Function ◽

Hippocampal Volume ◽

Cognitive Testing ◽

Pet Scan ◽

Aging Brain ◽

Amyloid Pet ◽

Older Individuals ◽

Amyloid Burden ◽

Tau Pathology

ObjectiveTo identify the hippocampal subregions linking initial amyloid and tau pathology to memory performance in clinically normal older individuals, reflecting preclinical Alzheimer disease (AD).MethodsA total of 127 individuals from the Harvard Aging Brain Study (mean age 76.22 ± 6.42 years, 68 women [53.5%]) with a Clinical Dementia Rating score of 0, a flortaucipir tau-PET scan, a Pittsburgh compound B amyloid-PET scan, a structural MRI scan, and cognitive testing were included. From these images, we calculated neocortical, hippocampal, and entorhinal amyloid pathology; entorhinal and hippocampal tau pathology; and the volumes of 6 hippocampal subregions and total hippocampal volume. Memory was assessed with the selective reminding test. Mediation and moderation analyses modeled associations between regional markers and memory. Analyses included covariates for age, sex, and education.ResultsNeocortical amyloid, entorhinal tau, and presubiculum volume univariately associated with memory performance. The relationship between neocortical amyloid and memory was mediated by entorhinal tau and presubiculum volume, which was modified by hippocampal amyloid burden. With other biomarkers held constant, presubiculum volume was the only marker predicting memory performance in the total sample and in individuals with elevated hippocampal amyloid burden.ConclusionsThe presubiculum captures unique AD-related biological variation that is not reflected in total hippocampal volume. Presubiculum volume may be a promising marker of imminent memory problems and can contribute to understanding the interaction between incipient AD-related pathologies and memory performance. The modulation by hippocampal amyloid suggests that amyloid is a necessary, but not sufficient, process to drive neurodegeneration in memory-related regions.

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Are depressive symptomatology and self-focused attention associated with subjective memory impairment in older adults?

International Psychogeriatrics ◽

10.1017/s104161021300241x ◽

2014 ◽

Vol 26 (4) ◽

pp. 573-580 ◽

Cited By ~ 33

Author(s):

Juhee Chin ◽

Kyung Ja Oh ◽

Sang Won Seo ◽

Duk L. Na

Keyword(s):

Test Performance ◽

Memory Impairment ◽

Depressive Symptomatology ◽

Memory Performance ◽

Neuropsychological Test ◽

Focused Attention ◽

Subjective Memory Complaints ◽

Subjective Memory ◽

Subjective Memory Impairment ◽

Memory Complaints

ABSTRACTBackground:Subjective memory impairment (SMI) refers to conditions in which people complain of memory problems despite intact cognition. The primary purpose of the present study was to examine the roles of self-focused attention and depressive symptomatology in subjective memory complaints.Methods:One hundred and eight patients who visited a memory disorder clinic with complaints of memory decline, but who were found on subsequent neuropsychological assessment to have normal cognitive function, were recruited to participate in the study. The severity of subjective memory complaints was measured with the modified Multifactorial Memory Questionnaire. In addition, neuropsychological functions, self-focused attention, and depressive symptomatology were also assessed.Results:The results showed that the severity of SMI was not significantly correlated with any of the neuropsychological test scores except for the complex figure copy. The severity of SMI, however, was significantly correlated with self-focused attention and depressive symptomatology. Hierarchical regression analysis revealed that self-focused attention and depressive symptomatology significantly contributed to the severity of subjective memory complaints over and above the neuropsychological test performance. The interaction effects between self-focused attention/depressive symptomatology and objective memory performance on the severity of SMI were not significant.Conclusions:In conclusion, self-focused attention and depressive symptomatology appear to play important roles in the severity of SMI, even though it is not clear how these factors interact with objective memory performance. Clinical implications as well as limitations of the present study were discussed.

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Structural ‘connectomic’ alterations in the limbic system of multiple sclerosis patients with major depression

Multiple Sclerosis Journal ◽

10.1177/1352458514558474 ◽

2014 ◽

Vol 21 (8) ◽

pp. 1003-1012 ◽

Cited By ~ 27

Author(s):

Salvatore Nigro ◽

Luca Passamonti ◽

Roberta Riccelli ◽

Nicola Toschi ◽

Federico Rocca ◽

...

Keyword(s):

Multiple Sclerosis ◽

Major Depression ◽

Diffusion Tensor ◽

Negative Impact ◽

Brain Connectivity ◽

Strong Support ◽

Imaging Data ◽

Connectivity Patterns ◽

The Right ◽

Multiple Sclerosis Patients

Background: Major depression (MD) is a common psychiatric disorder in multiple sclerosis (MS). Despite the negative impact of MD on the quality of life of MS patients, little is known about its underlying brain mechanisms. Objective: We studied the whole-brain connectivity patterns that were associated with MD in MS. Alterations were mainly expected within limbic circuits. Methods: Diffusion tensor imaging data were collected in 20 MS patients with MD, 22 non-depressed MS patients and 16 healthy controls. We used deterministic tractography and graph analysis to study the white-matter connectivity patterns that characterized MS patients with MD. Results: We found that MD in MS was associated with increased local path length in the right hippocampus and right amygdala. Further analyses revealed that these effects were driven by an increased shortest distance between both the right hippocampus and right amygdala and a series of regions including the dorsolateral and ventrolateral prefrontal cortex, orbitofrontal cortex, sensory-motor cortices and supplementary motor area. Conclusion: Our data provide strong support for neurobiological accounts positing that MD in MS is mediated by abnormal ‘communications’ within limbic circuits. We also found evidence that MD in MS may be linked with connectivity alterations at the limbic-motor interface, a group of regions that translates emotions into survival-oriented behaviors.

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