Figure - available from: Frontiers in Neurology
This content is subject to copyright.
Statistical parametric map overlaid on an MRI template (neurological orientation, axial view), showing brain regions positively correlated with BNT.
Source publication
Objective: Cognitive impairment is an important feature in multiple sclerosis (MS) and has been associated to several Magnetic Resonance Imaging (MRI) markers, but especially brain atrophy. However, the relationship between specific neuropsychological tests examining several cognitive functions and brain volumes has been little explored. Furthermor...
Similar publications
Manually-administered massage can potently increase endogenous oxytocin concentrations and neural activity in social cognition and reward regions and intranasal oxytocin can increase the pleasantness of social touch. In the present study, we investigated whether intranasal oxytocin modulates behavioral and neural responses to foot massage applied m...
Topographical disorientation refers to the selective inability to orient oneself in familiar surroundings. However, to date its neural correlates remain poorly understood. Here we use quantitative lesion analysis and a lesion network mapping approach in order to investigate seven patients with topographical disorientation. Our findings link not onl...
The adaptive calibration model suggests exposure to highly stressful or highly supportive early environments sensitizes the brain to later environmental input. We examined whether family and peer experiences predict neural sensitivity to social cues in 85 adolescent girls who completed a social feedback task during a functional brain scan and an in...
Previous studies have demonstrated the efficacy of metacognitive training (MCT) in schizophrenia. However, the underlying mechanisms related to therapeutic effect of MCT remain unknown. The present study explored the treatment effects of MCT on brain regional neural activity using regional homogeneity (ReHo) and whether these regions’ activities co...
Background: Mild cognitive impairment (MCI) represents a transitional state between normal aging and dementia disorders, especially Alzheimer's disease (AD). The disruption of the default mode network (DMN) is often considered to be a potential biomarker for the progression from MCI to AD. The purpose of this study was to assess MRI-specific change...
Citations
... Cognitive deficits are especially focused on attention and processing speed impairment, followed by executive function and episodic memory. MS is a recognized autoimmune disorder, and cognitive deficits have been linked to cortical and subcortical structural and functional brain damage 16,17 . ...
Post-COVID condition (PCC) and multiple sclerosis (MS) share some clinical and demographic features, including cognitive symptoms and fatigue. Some pathophysiological mechanisms well-known in MS, such as autoimmunity, neuroinflammation and myelin damage, have also been implicated in PCC. In this study, we aimed to compare the cognitive phenotypes of two large cohorts of patients with PCC and MS, and to evaluate the relationship between fatigue and cognitive performance. Cross-sectional study including 218 patients with PCC and 218 with MS matched by age, sex, and years of education. Patients were evaluated with a comprehensive neuropsychological protocol and were categorized according to the International Classification of Cognitive Disorders system. Fatigue and depression were also assessed. Cognitive profiles of PCC and MS largely overlapped, with a greater impairment in episodic memory in MS, but with small effect sizes. The most salient deficits in both disorders were in attention and processing speed. The severity of fatigue was greater in patients with PCC. Still, the correlations between fatigue severity and neuropsychological tests were more prominent in the case of MS. There were no differences in the severity of depression among groups. Our study found similar cognitive profiles in PCC and MS. Fatigue was more severe in PCC, but was more associated with cognitive performance in MS. Further comparative studies addressing the mechanisms related to cognitive dysfunction and fatigue may be of interest to advance the knowledge of these disorders and develop new therapies.
... MRI also generates the data necessary to perform subcortical morphometry. Subcortical morphometry is the preferred method to investigate the size and shape of subcortical structures in brain imaging and neurological research in an analytical manner [8]. This method processes MRI data to quantify the density and volume of specific areas of the brain, offering critical insights for the diagnosis, progression, treatment of neurological disorders, and morphological alterations including degeneration, hypertrophy and persistence and the specific morphological changes in this region displayed neurodegenerative disorders [9,10]. ...
... This method processes MRI data to quantify the density and volume of specific areas of the brain, offering critical insights for the diagnosis, progression, treatment of neurological disorders, and morphological alterations including degeneration, hypertrophy and persistence and the specific morphological changes in this region displayed neurodegenerative disorders [9,10]. Subcortical morphometry is often used by doctors and scientists to research neurological diseases such as Alzheimer's disease, Parkinson's disease, schizophrenia, and MS [8,9]. ...
Introduction
Multiple sclerosis (MS) is a chronic and autoimmune disease that has a significant influence on the central nervous system, such as the brain and spinal cord, affecting millions of individuals globally. Understanding the connection between subcortical brain regions and MS is crucial for effective diagnostic and therapeutic approaches for treating this disabling disease. This study explores the relationship between volume and contours of asymmetry index of subcortical brain regions in individuals with MS using volBrain software (https://www.volbrain.net; developed by José V. Manjón (Valencia Polytechnic University, Valencia, Spain) and Pierrick Coupé (University of Bordeaux, Bordeaux, France)).
Methods
In our retrospective investigation, we admitted 100 Turkish individuals, comprising 50 patients diagnosed with relapsing-remitting MS (RRMS) (24 (48%) males and 26 (52%) females) and 50 healthy controls (23 (46%) males and 27 (54%) females), registered between October 2017 and February 2022 for five years and underwent assessment in the radiology department at the Teaching and Research Hospital of Kocaeli University; 1,150 Turkish patients were excluded from our study based on our exclusion criteria. We used magnetic resonance imaging with a 3-Tesla (3T) scanner and volBrain software to assess volumes (cm³) and asymmetry indexes due to asymmetry for different levels of atrophy of total intracranial, total brain, gray matter, white matter, and subcortical regions, the most affected regions in MS patients for both patient and control cohorts.
Results
Statistical analysis revealed a significant difference between patient and control groups (p < 0.001), with patient group mean age at 38.32 years and control group mean age at 32.88 years. Patient group exhibited lower values for total intracranial, total brain, gray matter, white matter, and cerebrospinal fluid volume compared to control group (p < 0.05). The results indicated a statistically significant decrease (p < 0.05) in the values for total intracranial and total brain volume, whereas all other values remained unchanged. We compared volumes of subcortical structures on the right and left sides and found that the putamen, thalamus, and globus pallidus had statistically lower values in the patient group than in the control group (p < 0.001), apart from the lateral ventricle. Furthermore, our retrospective investigation demonstrated a statistically significant difference in the globus pallidus asymmetry index, indicating a preference for the patient group (p < 0.05). A lower asymmetry index value signifies a larger volume for the right side of the subcortical regions of the brain when compared to the left side.
Conclusion
Brain atrophy, although characterized by irreversible tissue damage, is targeted by therapeutic interventions to prevent progression. It is, therefore, imperative to develop a universally accepted measurement standard for subcortical structures that also considers the inherent variability present within each structure. Our findings serve as an important basis and indicator for the determination of subcortical atrophy and asymmetry in MS, the prognosis of the disease, and the etiology of clinical symptoms. Subsequent research may benefit by adopting the novel approach of considering brain atrophy as an outcome rather than a predictor, thereby facilitating the elucidation of the intricate biological mechanisms that give rise to volume loss.
... On the other hand, grey matter volume has increased in MS patients who have learnt a second language, which is suggestive of the efficacy of cognitive rehabilitation [21]. Matias-Guiu et al. [22] reported that semantic fluency results correlated with thalamus and caudate volumes in both hemispheres, while Crosson et al. [23] revealed that both left and right basal ganglia play a role in language generation. Total cortical volume might be perceived as a surrogate biomarker of cognitive reserve, and could in this way explain the fluctuations of the change over time. ...
Introduction:
Cognitive impairment occurs from the earliest stages of multiple sclerosis (MS) and progresses over time. The introduction of disease modifying therapies (DMTs) has changed the prognosis for MS patients, offering a potential opportunity for improvement in the cognitive arena as well.
Material and methods:
41 patients with relapsing-remitting multiple sclerosis (MS) were recruited to the study. Thirty patients were available for final follow-up and were included in the analysis. Baseline (BL) brain MRI including volumetry and neuropsychological tests were performed. Blood samples were collected at BL and follow-up (FU) and were tested for: vascular endothelial growth factor (VEGF), soluble vascular cell adhesion molecule-1 (sVCAM1), soluble platelet-endothelial CAM-1 (sPECAM1), and soluble intercellular CAM-1 (sICAM-1). Patients were invited for a final neuropsychological follow-up after a median of 6 years. Disease activity (relapses, EDSS increase, new/active brain lesions on MRI) was analysed between BL and FU.
Results:
The study group deteriorated in the Rey-Osterrieth Complex Figure (ROCF) test (p = 0.001), but improved significantly in three other tests, i.e. semantic fluency test (p = 0.013), California Verbal Learning Test (CVLT, p = 0.016), and Word Comprehension Test (WCT, p < 0.001). EDSS increase correlated negatively with semantic fluency and WCT scores (r = -0.579, p = 0.001 and r = -0.391, p = 0.033, respectively). Improvements in semantic fluency test and WCT correlated positively with baseline deep grey matter, grey matter, and cortical volumes (p < 0.05, r > 0). Higher EDSS on FU correlated significantly negatively with baseline left and right pallidum, right caudate, right putamen, right accumbens, and cortical volume (p < 0.05, r < 0). No significant relationship was found between the number of relapses and EDSS on FU or neuropsychological deteriorations. Improvements in WCT and CVLT correlated positively with baseline sPECAM1 and sVCAM1 results, respectively (r > 0, p < 0.05). Deterioration in ROCF test correlated significantly with higher levels of baseline VEGF and sVCAM1 (p < 0.05).
Conclusions:
Brain volume is an important predictor of future EDSS and cognitive functions outcome. MS patients have a potential for improving in neuropsychological tests over time. It remains to be established whether this is related to successful disease modification with immunotherapy. Baseline volumetric measures are stronger predictors of cognitive performance than relapse activity, which yet again highlights the importance of atrophy in MS prognosis.
... The thalamus has been suggested to play an important role in MS disease symptomatology, with lower volumes being predictive of clinical worsening [62], even in the early stages [63]. Basal ganglia changes have also frequently been observed and related to clinical change [64,65]. Additionally, our study showed that other subcortical regions, such as the amygdala, hippocampus, ventral diencephalon and nucleus accumbens, also show early-stage atrophy. ...
Recurrent neuroinflammation in relapsing-remitting MS (RRMS) is thought to lead to neurodegeneration, resulting in progressive disability. Repeated magnetic resonance imaging (MRI) of the brain provides non-invasive measures of atrophy over time, a key marker of neurodegeneration. This study investigates regional neurodegeneration of the brain in recently-diagnosed RRMS using volumetry and voxel-based morphometry (VBM). RRMS patients (N = 354) underwent 3T structural MRI <6 months after diagnosis and 1-year follow-up, as part of the Scottish multicentre 'FutureMS' study. MRI data were processed using FreeSurfer to derive volumetrics, and FSL for VBM (grey matter (GM) only), to establish regional patterns of change in GM and normal-appearing white matter (NAWM) over time throughout the brain. Volumetric analyses showed a decrease over time (q<0.05) in bilateral cortical GM and NAWM, cerebellar GM, brainstem, amygdala, basal ganglia, hippocampus, accumbens, thalamus and ventral diencephalon. Additionally, NAWM and GM volume decreased respectively in the following cortical regions, frontal: 14 out of 26 regions and 16/26; temporal: 18/18 and 15/18; parietal: 14/14 and 11/14; occipital: 7/8 and 8/8. Left GM and NAWM asymmetry was observed in the frontal lobe. GM VBM analysis showed three major clusters of decrease over time: 1) temporal and subcortical areas, 2) cerebellum, 3) anterior cingulum and supplementary motor cortex; and four smaller clusters within the occipital lobe. Widespread GM and NAWM atrophy was observed in this large recently-diagnosed RRMS cohort, particularly in the brainstem, cerebellar GM, and subcortical and occipital-temporal regions; indicative of neurodegeneration across tissue types, and in accord with limited previous studies in early disease. Volumetric and VBM results emphasise different features of longitudinal lobar and loco-regional change, however identify consistent atrophy patterns across individuals. Atrophy measures targeted to specific brain regions may provide improved markers of neurodegeneration, and potential future imaging stratifiers and endpoints for clinical decision making and therapeutic trials.
... Compared to HC, CW MS patients showed bilateral superior frontal gyrus and right caudate nucleus GM atrophy, while compared to CS, they showed more severe GM atrophy of right anterior cingulate cortex and bilateral supplementary motor area. The clinical relevance of GM atrophy in the frontal cortex, anterior cingulate cortex and caudate nucleus for cognitive performance has been consistently found in several cross-sectional studies [71][72][73][74]. Progression of caudate atrophy was associated with worse SDMT performance over a median follow-up of 20 months [27], whereas more severe atrophy of the caudate nucleus and anterior cingulate cortex was found in MS patients compared to those without cognitive deterioration over 5 years [25]. ...
Background
Heterogeneous processes may contribute to cognitive impairment in multiple sclerosis (MS).
Objective
To apply a longitudinal multiparametric MRI approach to identify mechanisms associated with cognitive worsening in MS patients.
Methods
3 T brain functional and structural MRI scans were acquired at baseline and after a median follow-up of 3.4 years in 35 MS patients and 22 healthy controls (HC). Associations between cognitive worsening (reliable change index score < − 1.25 at the Rao’s battery) and longitudinal changes in regional T2-hyperintense white matter (WM) lesions, diffusion tensor microstructural WM damage, gray matter (GM) atrophy and resting state (RS) functional connectivity (FC) were explored.
Results
At follow-up, HC showed no clusters of significant microstructural WM damage progression, GM atrophy or changes in RS FC. At follow-up, 10 MS patients (29%) showed cognitive worsening. Compared to cognitively stable, cognitively worsened MS patients showed more severe GM atrophy of the right anterior cingulate cortex and bilateral supplementary motor area (p < 0.001). Cognitively worsened vs cognitively stable MS patients showed also decreased RS FC in the right hippocampus of the right working memory network and in the right insula of the default mode network. Increased RS FC in the left insula of the executive control network was found in the opposite comparison (p < 0.001). No significant regional accumulation of focal WM lesions nor microstructural WM abnormalities occurred in both patients’ groups.
Conclusions
GM atrophy progression in cognitively relevant brain regions combined with functional impoverishment in networks involved in cognitive functions may represent the substrates underlying cognitive worsening in MS.
... Research on verbal fluency in pwMS also provided evidence for the distinction between phonemic and semantic fluency, showing several patterns of impairment and different neural bases (e.g., Matías-Guiu et al. 2018). For instance, phonemic verbal fluency was more impaired than semantic verbal fluency in relapsingremitting MS phenotype (e.g., Brissart et al., 2013), whereas both fluency tasks were found to be impaired in pwMS with primary and secondary progressive phenotypes who suffer from more global cognitive impairment (e.g., Huijbregts et al., 2004). ...
Objective
Executive functioning (EF) can be one of the earliest, despite under-detected, impaired cognitive domains in patients with multiple sclerosis (pwMS). However, it is still not clear the role of EF on verbal fluency tests given the presence of information processing speed (IPS) deficits in pwMS.
Method
Performance of a group of 43 pwMS without IPS impairment as measured with the Symbol Digit Modalities Test (SDMT) and a group of 32 healthy controls (HC) was compared on the Phonemic and Semantic Fluency Tests. For each group, we scored the number of words generated (i) in the early time interval (i.e., first 15 sec, semi-automatic process) and (ii) in the late time interval (i.e., from 15 to 60 sec, controlled process).
Results
Globally, pwMS produced significantly fewer words than HC on the Phonemic but not on the Semantic Fluency Test. Crucially, in the Phonemic Fluency Test pwMS generated significantly fewer words than HC in the late time interval, whereas no significant difference between the two groups emerged in the early time interval.
Conclusions
These findings suggest that executive dysfunction is the core element on the Phonemic Fluency Test also in pwMS and it deserves attention in both research and clinical practice.
... Noteworthy, our findings suggest that the SRT and 10/36 SPART may be the most useful and sensitive memory tests in MS, consistent with previous reports that greatly encouraged assessing memory impairments with these tools in MS (Sousa et al., 2021). In addition, our EFA results underline the need to assess both phonological and semantic verbal fluency separately, in accordance with previous behavioral and neuroimaging studies that show as the two types of verbal fluency may be related to distinct sets of cognitive processes (e.g., semantic vs. phonological memory, clustering vs. switching strategies; see Rende et al., 2002;Unsworth et al., 2011) and involve different cortical and subcortical areas (e.g., temporal vs. frontal lobes, thalamus and putamen vs. caudate nucleus; see Baldo et al., 2006Baldo et al., , 2010Matías-Guiu et al., 2018;Delgado-Álvarez et al., 2021). ...
Background
: Cognitive impairment (CI) is common in Multiple Sclerosis (MS), and its prevalence rate ranges between 22% and 70%. Because CI significantly impacts vocational status, caregiver burden, and quality of life, an accurate neuropsychological assessment is required. Three widely used and validated batteries for MS-associated CI are the Brief Repeatable Neuropsychological Battery (BRN-B), the Minimal Assessment of Cognitive Function (MACFIMS), and the Brief International Cognitive Assessment (BICAMS). Although similar, these batteries differ in time-consuming and in specific tests employed. This study aims to assess the sensitivity of cognitive tests included in these batteries through an Item Response Theory approach.
Methods
: Ninety-seven patients with MS and 91 demographically matched controls (HC) were consecutively assessed using the three neuropsychological batteries (i.e., BRN-B, MACFIMS, and BICAMS). Continuous Response Model (CRM) was used to identify the cognitive test(s) that best discriminate patients with MS from HC. Receiver Operating Characteristic (ROC) curve analysis was used to determine the accuracy of the CRM results.
Results
: Cognitive tests loaded on two different latent variables: the ‘higher-order executive functioning,’ consisting of tests assessing concept formation, problem-solving, and inhibitory control, and the ‘memory and information processing speed,’ comprising tests assessing long-term, working memory, and information processing speed. The Delis Kaplan Executive Functioning System-Sorting Test and the Stroop Test were the most sensitive tests in differentiating cognitive functioning between MS and HC.
Conclusions
: This study confirms the importance of including a more extensive executive assessment in MS clinical practice since higher-order executive functions (e.g., abstraction and inhibitory control) significantly impact patients’ quality of life and functional autonomy. Clinical implications of careful dissection of executive functioning in MS neuropsychological assessment are discussed.
... Future, larger studies could consider lesion volumes, underlying disease, left hemisphere lesions, and other variables to obtain a more comprehensive picture. Our study did not focus on any specific brain area as complex cognitive mechanisms involve the coordination of networks involving the whole brain (Matías-Guiu et al., 2018;Pessoa, 2010). Follow-up studies targeting brain areas crucial for pragmatic processing could lend better insights. ...
Background:
While pragmatic deficits are well documented in patients with schizophrenia (SCZ) and right hemisphere damage (RHD), there is a paucity of research comparing the pragmatic deficits of these two groups. Do they experience similar cognitive dysfunction or is there a dissociation between the two patient groups?
Aims:
To investigate the nature of pragmatic deficits in these two groups and to gain an understanding of the underlying cognitive mechanisms that might be associated with these deficits to further future investigations.
Methods & procedures:
A total of 60 participants (15 patients with SCZ; 15 with RHD; 30 (15 + 15) healthy controls (HC) were administered the Bengali Audio-Visual Test-Battery for Assessment of Pragmatic Skills.
Outcomes & results:
Both SCZ and RHD patients were found to have significant pragmatic deficits compared with their matched controls. SCZ patients were found to score significantly better than the RHD group in six out of the 10 pragmatic skills when controlled for age and education. Discriminant function analysis was performed and 86.7% of the cases (HC = 100%, SCZ = 73.3% and RHD = 86.7%) were correctly reclassified into their original categories using the test scores.
Conclusions & implications:
The study suggests that there is heterogeneity in the nature of the pragmatic breakdown within and across patient groups. Therefore, individualized restorative measures targeting the disrupted cognitive mechanism(s) might help elevate pragmatic competence and enhance the social functioning of patients with pragmatic deficits.
What this paper adds:
What is already known on the subject Pragmatic deficits are common in adults with cognitive impairments of different etiologies. However, few studies have explored pragmatic deficits across clinical populations. Consequently, very little is known about the nature of pragmatic deficits in patients with schizophrenia and right hemisphere damage. What this paper adds to existing knowledge This work offers preliminary data on pragmatic difficulties in patients with schizophrenia and right hemisphere damage. This study overrides the boundaries of traditional classifications and evaluates pragmatic difficulties in these two clinical populations with reference to the underlying cognitive mechanisms, which might be disrupted. What are the potential or actual clinical implications of this work? The study adds a transdiagnostic perspective suggesting that there might be heterogeneity in pragmatic deficits, both within and across patient groups, and stresses the need for individualized therapy.
... The SDMT has been shown to be an early predictor of disease onset in premanifest HD [31], therefore it could reflect disease onset in this analysis (i.e., with participants showing reduced financial capacity being closer to disease onset than those who remain autonomous). Interestingly, the SDMT is associated with activation in several brain regions known to be affected early in HD such as the caudate nucleus, frontal lobe, insula and posterior cingulate [32], which are also regions implicated in financial decision making [33,34]. However, future work will be needed to investigate this further. ...
Objectives
Huntington’s disease (HD) is a neurodegenerative disease in which cognitive and behavioural symptoms impair the performance of instrumental activities of daily living, including the handling of finances. We sought to determine the prevalence of financial dysfunction in HD, and the demographic and clinical predictors of such impairments.
Methods
We analysed longitudinal data for pre-manifest gene carriers and HD patients from the Enroll-HD dataset. Financial dysfunction was determined by finance-related items in the Total Functional Capacity (TFC) and Functional Assessment (FA) scales. A binary logistical regression model was used to investigate the predictive value of demographic and clinical factors for the development of financial dysfunction.
Results
Financial impairment was found to be common in HD gene carriers, and over half required financial assistance within 5 years from diagnosis. Cognitive impairment, apathy, unemployment and disease severity predicted financial dysfunction in manifest patients. For pre-manifest patients, the predictors were proximity to disease onset and depression.
Conclusions
Loss of financial autonomy is common in HD, and cognitive and psychiatric factors are important in its development. Clinicians must be vigilant to identify patients that may be vulnerable to financial exploitation.
... MR-morphometry technique provides an opportunity for a detailed study of metric parameters of various brain structures in neurodegenerative and demyelinating brain diseases [6], including MS with proven thalamic atrophy [7][8][9][10][11][12][13], in some cases, affecting the clinical performance. The recently created in 2018 advanced software allows one to evaluate volumetric changes not only in the thalamus as a whole, but also in its individual nuclear groups [14]. ...
Objectives
To define both the severity and extent of structural alteration in certain thalamic nuclei by means of MR morphometry and to compare these findings with clinical performance in different phenotypes of multiple sclerosis (MS).
Methods
We comparatively measured the thalamus nuclei volumes of patients with remitting-relapsing (RRMS) and secondary-progressive (SPMS) phenotypes of multiple sclerosis and healthy control subjects (HC). The evaluation of neurological performance was based on the results of Expanded Disability Status Scale and Multiple Sclerosis Severity Scale. Cognitive and mental state was rated according to the results of Mini-Mental State Examination, Frontal Assessment Battery, Montreal Cognitive Assessment and Symbol Digit Modalities Test. Freesurfer 6.0 was used for thalamic nuclei volumes calculation.
Results
The median volume decline in thalamic pulvinar nuclei in RRMS group on the left side (anterior nucleus − 186,6 mm³, posterior nucleus – 149,4 mm³, medial nucleus 852,4 mm³) compared to HC (anterior nucleus – 229,2 mm³, posterior nucleus – 187,5 mm³, medical nucleus – 1081,3 mm³). Same group, right side – anterior nucleus – 219,5 mm³, posterior nucleus 187,1 mm³, medial nucleus – 989,6 mm³; HC group – anterior nucleus 261,1 mm³, posterior nucleus 240,5 mm³, medial nucleus – 1196,7 mm³ (p < 0,05). The highest correlation of the written section of SDMT was observed with the left ventral anterior nucleus (r = 0,71).
Conclusion
These findings indicate the credible correlation between clinical progression of neurological and cognitive impairment in MS patients with asymmetry left-sided thalamic nuclei atrophy and may be considered a potential predicting tool of MS progression.
