Prominent role of executive functioning on the Phonemic Fluency Test in people with multiple sclerosis.

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.

Slowing processing speed is associated with cognitive fatigue in newly diagnosed multiple sclerosis patients.

OBJECTIVE: To further investigate objective measures of cognitive fatigue (CF), defined as the inability to sustain performance over time, in newly diagnosed multiple sclerosis (MS) patients, by conducting a performance analysis on the Paced Auditory Serial Addition Test (PASAT) based on the type of errors (omissions vs. incorrect responses) committed. METHOD: Sixty-two newly diagnosed patients with MS (pwMS) and 41 healthy controls (HC) completed the PASAT. Analysis of the change in performance during the test was performed by comparing the number of correct responses, incorrect responses, and omissions in the 1st versus the 3rd tertile of the PASAT. RESULTS: A significant decline in accuracy over time was observed to be related to an increment in the number of omissions, significantly more pronounced in pwMS than in HC. No change in the number of incorrect responses throughout the PASAT was observed for either group. CONCLUSIONS: CF can be detected even in newly diagnosed pwMS and might objectively manifest as a progressive increase in omissions during a sustained highly demanding task (i.e., PASAT). This pattern may reflect slowed processing speed and increased fatigue in pwMS. Focusing on omissions on the PASAT instead of correct responses only may improve its specificity as an objective measure of CF.

Cerebrospinal fluid inflammatory profile of cognitive impairment in newly diagnosed multiple sclerosis patients.

BACKGROUND: The cerebrospinal fluid (CSF) molecular milieu is a marker of diffuse intrathecal inflammation in the meninges that, in turn, targets the grey matter (GM) in multiple sclerosis (MS). Cognitive impairment (CI) is associated with brain damage in MS and is often present early in people with MS (pwMS). OBJECTIVE: To investigate whether a specific CSF inflammatory profile is associated with different degrees of CI in newly diagnosed pwMS. METHODS: Sixty-nine pwMS and 43 healthy controls (HCs) underwent neuropsychological testing. The presence and levels of 57 inflammatory mediators in the CSF were assessed. RESULTS: Apparently cognitively normal (ACN) pwMS had impaired executive functioning compared to HCs but performed better than pwMS with mild and severe CI (mCI and sCI) in all tests. CSF mediators involving innate immunity and immune activation and recruitment, differentiate ACN from pwMS with mCI, while CSF mediators related to B- and T-cell immunity and chemotaxis differentiate both ACN and mCI from those with sCI. CXCL13 was the only molecule that differentiated sCI from mCI pwMS. CONCLUSION: Specific CSF molecular patterns, reflecting the involvement of both innate and adaptive immune responses, are associated with the severity of CI in newly diagnosed pwMS.

Unraveling the MRI-Based Microstructural Signatures Behind Primary Progressive and Relapsing-Remitting Multiple Sclerosis Phenotypes.

BACKGROUND: The mechanisms driving primary progressive and relapsing-remitting multiple sclerosis (PPMS/RRMS) phenotypes are unknown. Magnetic resonance imaging (MRI) studies support the involvement of gray matter (GM) in the degeneration, highlighting its damage as an early feature of both phenotypes. However, the role of GM microstructure is unclear, calling for new methods for its decryption. PURPOSE: To investigate the morphometric and microstructural GM differences between PPMS and RRMS to characterize GM tissue degeneration using MRI. STUDY TYPE: Prospective cross-sectional study. SUBJECTS: Forty-five PPMS (26 females) and 45 RRMS (32 females) patients. FIELD STRENGTH/SEQUENCE: 3T scanner. Three-dimensional (3D) fast field echo T1-weighted (T1-w), 3D turbo spin echo (TSE) T2-w, 3D TSE fluid-attenuated inversion recovery, and spin echo-echo planar imaging diffusion MRI (dMRI). ASSESSMENT: T1-w and dMRI data were employed for providing information about morphometric and microstructural features, respectively. For dMRI, both diffusion tensor imaging and 3D simple harmonics oscillator based reconstruction and estimation models were used for feature extraction from a predefined set of regions. A support vector machine (SVM) was used to perform patients' classification relying on all these measures. STATISTICAL TESTS: Differences between MS phenotypes were investigated using the analysis of covariance and statistical tests (P < 0.05 was considered statistically significant). RESULTS: All the dMRI indices showed significant microstructural alterations between the considered MS phenotypes, for example, the mode and the median of the return to the plane probability in the hippocampus. Conversely, thalamic volume was the only morphometric feature significantly different between the two MS groups. Ten of the 12 features retained by the selection process as discriminative across the two MS groups regarded the hippocampus. The SVM classifier using these selected features reached an accuracy of 70% and a precision of 69%. DATA CONCLUSION: We provided evidence in support of the ability of dMRI to discriminate between PPMS and RRMS, as well as highlight the central role of the hippocampus. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

Coping Strategies and Their Impact on Quality of Life and Physical Disability of People with Multiple Sclerosis.

The aim of the study is to investigate the impact of coping strategies on Health-Related Quality of Life (HRQoL) and physical disability assessed with the Expanded Disability Status Scale (EDSS) of people with multiple sclerosis (pwMS). PwMS were asked to focus on "MS diagnosis" as the core stressor. One hundred eight pwMS completed the Coping Responses Inventory-Adult form (CRI-Adult), the Multiple Sclerosis Quality of Life-29 (MSQoL-29), and the Depression Anxiety Stress Scale-21 (DASS-21). Multiple regression analyses (first block: EDSS, disease duration, and DASS-21) revealed that physical MSQoL-29 was positively associated with Alternative Rewards and negatively with Resigned Acceptance of the CRI-Adult. The mental MSQoL-29 was positively associated with Problem-Solving and negatively with Emotional Discharge. The Expanded Disability Status Scale (EDSS; first block: disease duration and general distress) was negatively associated with Positive Reappraisal. The Analysis of covariance (ANCOVA) revealed that pwMS with lower physical disability showed higher scores in Positive Reappraisal and lower scores in Emotional Discharge than pwMS with a higher physical disability. Coping strategies can play a role on HRQoL and physical disability in pwMS above and beyond EDSS, disease duration, and general distress. Psychological interventions should be considered in pwMS since the time of diagnosis to promote engagement in adaptive coping strategies and contrast the maladaptive ones.

Microstructural MRI Correlates of Cognitive Impairment in Multiple Sclerosis: The Role of Deep Gray Matter.

Although cognitive impairment (CI) is frequently observed in people with multiple sclerosis (pwMS), its pathogenesis is still controversial. Conflicting results emerged concerning the role of microstructural gray matter (GM) damage especially when involving the deep GM structures. In this study, we aimed at evaluating whether differences in cortical and deep GM structures between apparently cognitively normal (ACN) and CI pwMS (36 subjects in total) are present, using an extensive set of diffusion MRI (dMRI) indices and conventional morphometry measures. The results revealed increased anisotropy and restriction over several deep GM structures in CI compared with ACN pwMS, while no changes in volume were present in the same areas. Conversely, reduced anisotropy/restriction values were detected in cortical regions, mostly the pericalcarine cortex and precuneus, combined with reduced thickness of the superior frontal gyrus and insula. Most of the dMRI metrics but none of the morphometric indices correlated with the Symbol Digit Modality Test. These results suggest that deep GM microstructural damage can be a strong anatomical substrate of CI in pwMS and might allow identifying pwMS at higher risk of developing CI.

Social Cognition in Multiple Sclerosis: A 3-Year Follow-Up MRI and Behavioral Study.

Social cognition (SC) has become a topic of widespread interest in the last decade. SC deficits were described in multiple sclerosis (MS) patients, in association with amygdala lesions, even in those without formal cognitive impairment. In this 3-year follow-up study, we aimed at longitudinally investigating the evolution of SC deficits and amygdala damage in a group of cognitive-normal MS patients, and the association between SC and psychological well-being. After 3 years (T3) from the baseline examination (T0), 26 relapsing-remitting MS patients (RRMS) were retested with a neuropsychological battery and SC tasks (theory of mind, facial emotion recognition, empathy). A SC composite score (SCcomp) was calculated for each patient. Emotional state, fatigue, and quality of life (QoL) were also evaluated. RRMS patients at T3 underwent a 3T-MRI as performed at T0, from which were calculated both volume and cortical lesion volume (CLV) of the amygdalae. Compared to T0, at T3 all RRMS patients were still cognitive-normal and remained stable in their global SC impaired performance. At T0, SCcomp correlated with amygdala CLV (p = 0.002) while, at T3, was more associated with amygdala volume (p = 0.035) rather than amygdala CLV (p = 0.043). SCcomp change T3-T0 correlated with global emotional state (p = 0.043), depression (p = 0.046), anxiety (p = 0.034), fatigue (p = 0.025), and QoL-social functioning (p = 0.033). We showed the longitudinal stability of SC deficits in cognitive-normal RRMS patients, mirroring the amygdala structural damage and the psychological well-being. These results highlight that SC exerts a key role in MS.

A Videogame-Based Approach to Measuring Information Processing Speed in Multiple Sclerosis Patients.

Objective: Slowing information processing speed (IPS) is a biomarker of neuronal damage in patients with multiple sclerosis (pwMS). A focus on IPS might be the ideal solution in the perspective of promptly detecting cognitive changes over time. We developed a tablet-based home-made videogame to test the sensitivity of this device in measuring subclinical IPS in pwMS. Materials and Methods: Forty-three pwMS without cognitive impairment and 20 healthy controls (HCs) were administered the videogame task with a tablet. Response times (RTs) and accuracy were recorded. Results: PwMS (mean RTs = 505.5 ± 73.9 ms) were significantly slower than HCs (mean RTs = 462.3 ± 40.3 ms, P = 0.014) on the videogame task. A moderate but significant correlation (r = -0.35, P = 0.03) between mean RTs and the Symbol Digit Modalities Test was observed. Conclusion: Our videogame showed good sensitivity in measuring IPS in apparently cognitive normal pwMS. Computerized testing might be useful in screening initial cognitive dysfunction that should be monitored as a marker of underlying disease progression. IRB approval Number is 2332CESC.

CSF parvalbumin levels reflect interneuron loss linked with cortical pathology in multiple sclerosis.

INTRODUCTION AND METHODS: In order to verify whether parvalbumin (PVALB), a protein specifically expressed by GABAergic interneurons, could be a MS-specific marker of grey matter neurodegeneration, we performed neuropathology/molecular analysis of PVALB expression in motor cortex of 40 post-mortem progressive MS cases, with/without meningeal inflammation, and 10 control cases, in combination with cerebrospinal fluid (CSF) assessment. Analysis of CSF PVALB and neurofilaments (Nf-L) levels combined with physical/cognitive/3TMRI assessment was performed in 110 naïve MS patients and in 32 controls at time of diagnosis. RESULTS: PVALB gene expression was downregulated in MS (fold change = 3.7 ± 1.2, P < 0.001 compared to controls) reflecting the significant reduction of PVALB+ cell density in cortical lesions, to a greater extent in MS patients with high meningeal inflammation (51.8, P < 0.001). Likewise, post-mortem CSF-PVALB levels were higher in MS compared to controls (fold change = 196 ± 36, P < 0.001) and correlated with decreased PVALB+ cell density (r = -0.64, P < 0.001) and increased MHC-II+ microglia density (r = 0.74, P < 0.01), as well as with early age of onset (r = -0.69, P < 0.05), shorter time to wheelchair (r = -0.49, P < 0.05) and early age of death (r = -0.65, P < 0.01). Increased CSF-PVALB levels were detected in MS patients at diagnosis compared to controls (P = 0.002). Significant correlation was found between CSF-PVALB levels and cortical lesion number on MRI (R = 0.28, P = 0.006) and global cortical thickness (R = -0.46, P < 0.001), better than Nf-L levels. CSF-PVALB levels increased in MS patients with severe cognitive impairment (mean ± SEM:25.2 ± 7.5 ng/mL) compared to both cognitively normal (10.9 ± 2.4, P = 0.049) and mild cognitive impaired (10.1 ± 2.9, P = 0.024) patients. CONCLUSIONS: CSF-PVALB levels reflect loss of cortical interneurons in MS patients with more severe disease course and might represent an early, new MS-specific biomarker of cortical neurodegeneration, atrophy, and cognitive decline.

Pitch height and brightness both contribute to elicit the SMARC effect: a replication study with expert musicians.

Pitch-height can be represented in a spatial format. Reaction times (RTs) to lower pitch-heights are faster when responses are executed in the lower side of space, whereas RTs to higher pitch-heights are faster when responses are executed in the upper side of space. This effect is called the Spatial-Music Association of Response Codes (SMARC) effect. We investigated how pitch-height and the brightness of a tone's timbre might contribute in eliciting the SMARC effect as a function of music expertise by comparing the results of 24 musicians with the results we gathered previously (Pitteri et al., 2017) with 24 non-musicians. Three experimental conditions were used: pitch-height varied, brightness varied; pitch-height varied, brightness fixed; pitch-height fixed, brightness varied. We found that the coherent modulation of both pitch-height and brightness elicited the strongest SMARC effect, independently of music expertise. These results add evidence to the hypothesis that the strongest SMARC effect does not belong to pitch-height or brightness, but to pitch-height and brightness together.

Visual-Attentional Load Unveils Slowed Processing Speed in Multiple Sclerosis Patients: A Pilot Study with a Tablet-Based Videogame.

Slowing in information processing speed (IPS) is the key cognitive deficit in multiple sclerosis (MS). Testing IPS in different cognitive load conditions by using computerized tools might reveal initial IPS slowness underestimated by classic paper-and-pencil tests. To investigate the extent to which IPS can be affected by increased task demands, we developed three tasks based on the manipulation of the visual-attentional load, delivered with a home-made, tablet-based videogame. Fifty-one patients with MS (pwMS), classified as having no cognitive impairment in classic paper-and-pencil tests, and 20 healthy controls (HC) underwent the videogame tasks; reaction times (RTs) and accuracy were recorded. A significant reduced performance of pwMS as compared with HC was found on the videogame tasks, with pwMS being on average slower and less accurate than HC. Furthermore, pwMS showed a significantly more pronounced decrement in accuracy as a function of the visual-attentional load, suggesting a higher susceptibility to increased task demands. Significant correlations among the Symbol Digit Modalities Test (SDMT) and the videogame mean RTs and accuracy were found, providing evidence for the concurrent validity of the videogame as a valid tool to test IPS in pwMS. The high potential that might derive from the adoption of computerized assessment tools in clinical practice should be taken into consideration and investigated further.

The CSF Profile Linked to Cortical Damage Predicts Multiple Sclerosis Activity.

OBJECTIVE: Intrathecal inflammation correlates with the grey matter damage since the early stages of multiple sclerosis (MS), but whether the cerebrospinal fluid (CSF) profile can help to identify patients at risk of disease activity is still unclear. METHODS: We evaluated the association between CSF levels of 18 cytokines, previously found to be associated to grey matter damage, and the disease activity, among 99 patients with relapsing-remitting MS, who underwent blinded clinical and 3 T magnetic resonance imaging (MRI) evaluations for 4 years. Groups with evidence of disease activity (EDA) or no evidence of disease activity (NEDA; occurrence of relapses, new white matter lesions, and Expanded Disability Status Scale [EDSS] change) were identified. Cortical lesions and the annualized cortical thinning were also evaluated. RESULTS: Forty-one patients experienced EDA and, compared to the NEDA group, had at diagnosis higher CSF levels of CXCL13, CXCL12, IFNγ, TNF, sCD163, LIGHT, and APRIL (p < 0.001). In the multivariate analysis, CXCL13 (hazard ratio [HR] = 1.35; p = 0.0002), LIGHT (HR = 1.22; p = 0.005) and APRIL (HR = 1.78; p = 0.0001) were the CSF molecules more strongly associated with the risk of EDA. The model, including CSF variables, predicted more accurately the occurrence of disease activity than the model with only clinical/MRI parameters (C-index at 4 years = 71% vs 44%). Finally, higher CSF levels of CXCL13 (ß = 4.7*10-4 ; p < 0.001), TNF (ß = 3.1*10-3 ; p = 0.004), LIGHT (ß = 2.6*10-4 ; p = 0.003), sCD163 (ß = 4.3*10-3 ; p = 0.009), and TWEAK (ß = 3.4*10-3 ; p = 0.024) were associated with more severe cortical thinning. INTERPRETATION: A specific CSF profile, mainly characterized by elevated levels of B-cell related cytokines, distinguishes patients at high risk of disease activity and severe cortical damage. The CSF analysis may allow stratifications of patients at diagnosis for optimizing therapeutic approaches. ANN NEUROL 2020;88:562-573.

False memories in relapsing remitting multiple sclerosis patients: A preliminary investigation with the DRM paradigm.

BACKGROUND: Memory impairment is one of the most frequently and early detected impairment in multiple sclerosis (MS) patients. Several authors have argued that when a failure occurs in the retrieval of lexical information, this might be due to a reduction of the lexical pool, related to semantic memory. Here we further investigated memory alteration in MS patients, by focusing on memory distortions (i.e., false memories) for semantically-related material. METHODS: A group of 40 consecutive relapsing remitting MS (RRMS) patients and a matched control group of 40 healthy controls performed the Deese-Roediger-McDermott (DRM), a false memory task for lists of associated words. RESULTS: At recall, RRMS patients reported a reduced number of false recalls for semantically-related but non-presented items (i.e., critical false recalls) compared to HCs; at recognition, RRMS patients showed a reduced level of confidence for false recognitions of critical items. CONCLUSION: We found a reduced susceptibility to false memories in RRMS patients compared to HCs. The potential mechanisms underlying this effect are discussed in light of the alterations in the structure of semantic memory.

Executive functioning affects verbal learning process in multiple sclerosis patients: Behavioural and imaging results.

Verbal learning and memory deficits are among the most frequent in people with multiple sclerosis (pwMS) and have been shown to be affected by deficits in other cognitive domains, such as information processing speed and executive functioning (EF). In the present study, we aimed to further investigate the differential impact that EF may exert on verbal learning and memory on both behavioural and neural levels. Seventy pwMS were assessed with a comprehensive battery of neuropsychological tests, including tests of verbal memory (Selective Reminding Test; SRT) and EF (Stroop test; Phonemic and Alternate Verbal Fluency; Modified Five-Point Test). Structural 3Tesla magnetic resonance imaging (MRI) scans were available for 68 patients; cortical thickness of several frontal, pre-frontal, and hippocampal regions was calculated. Multivariable linear regression analysis showed that patients' performance on Alternate Fluency Test predicted both their immediate (SRT-LTS: R2  = .38; p < .001; SRT-CLTR: R2  = .42; p < .001) and delayed (SRT-D: R2  = .39; p < .001) verbal memory performance. In addition, we found a significant relationship between the cortical thickness of the hippocampus and several bilateral frontal areas (i.e., anterior cingulate gyrus, superior and inferior frontal gyrus, medial frontal cortex, and frontal pole) with verbal memory tests scores (SRT-LTS: R2  = .45; p < .001; SRT-CLTR: R2  = .52; p < .001; SRT-D: R2  = .49; p < .001). These behavioural and MRI results suggest that EF significantly impacts verbal memory performance in pwMS. The understanding of the complex interaction between these distinct cognitive domains can help foster the development of memory rehabilitation paradigms that take into account also the role of executive functioning.

Lost in Classification: Lower Cognitive Functioning in Apparently Cognitive Normal Newly Diagnosed RRMS Patients.

Cognitive functioning in multiple sclerosis (MS) patients is usually related to the classic, dichotomic classification of impaired vs. unimpaired cognition. However, this approach is far from mirroring the real efficiency of cognitive functioning. Applying a different approach in which cognitive functioning is considered as a continuous variable, we aimed at showing that even newly diagnosed relapsing-remitting MS (RRMS) patients might suffer from reduced cognitive functioning with respect to a matched group of neurologically healthy controls (HCs), even if they were classified as having no cognitive impairment (CI). Fifty newly diagnosed RRMS patients and 36 HCs were tested with an extensive battery of neuropsychological tests. By using Z-scores applied to the whole group of RRMS and HCs together, a measure of cognitive functioning (Z-score index) was calculated. Among the 50 RRMS patients tested, 36 were classified as cognitively normal (CN). Even though classified as CN, RRMS patients performed worse than HCs at a global level (p = 0.004) and, more specifically, in the domains of memory (p = 0.005) and executive functioning (p = 0.006). These results highlight that reduced cognitive functioning can be present early in the disease course, even in patients without an evident CI. The current classification criteria of CI in MS should be considered with caution.

Ipsilesional Impairments of Visual Awareness After Right-Hemispheric Stroke.

Unilateral brain damage following stroke frequently hampers the processing of contralesional space. Whether and how it also affects the processing of stimuli appearing on the same side of the lesion is still poorly understood. Three main alternative hypotheses have been proposed, namely that ipsilesional processing is functionally (i) hyperefficient, (ii) impaired, or (iii) spared. Here, we investigated ipsilesional space awareness through a computerized paradigm that exploits a manipulation of concurrent information processing demands (i.e., multitasking). Twelve chronic right-hemisphere stroke patients with a total lack of awareness for the contralesional side of space were administered a task that required the spatial monitoring of two locations within the ipsilesional hemispace. Targets were presented immediately to the right of a central fixation point (3° eccentricity), or farther to the right toward the screen edge (17° eccentricity), or on both locations. Response to target position occurred either in isolation or while performing a concurrent visual or auditory task. Results showed that most errors occurred when two targets were simultaneously presented and patients were faced with additional task demands (in the visual or auditory modalities). In the context of concurrent visual load, ipsilesional targets presented at the rightmost location were omitted more frequently than those presented closer to fixation. This pattern qualifies ipsilesional processing in right-hemisphere stroke patients as functionally impaired, arguing against the notion of ipsilesional hyperperformance, especially when under visual load.

Social cognition deficits and the role of amygdala in relapsing remitting multiple sclerosis patients without cognitive impairment.

BACKGROUND: Social cognition (SC) can be impaired in multiple sclerosis (MS) patients; however, most studies have not controlled for generalized cognitive impairment (CI), nor have they examined the role of the amygdala using advanced structural neuroimaging. Whether deficits in SC occur in the disease even before the concomitant manifestation of CI, with a specific interest in the role of bilateral amygdala. METHODS: In this study, we enrolled 31 RRMS patients and 38 healthy controls (HC). SC was examined with the Reading the Mind in the Eyes (RME), a task of facial affect recognition (FAR), and the empathy quotient (EQ). 3T MRI scans were obtained for all patients with special interest in quantifying amygdala lesions by cortical lesion volume (CLV) estimation. RESULTS: The results showed that the RRMS group did worse as compared to HC in the RME (p < .001), the FAR task (p = .001), and the EQ (p = .022). Patients had mainly difficulties in recognition the negative emotions of fear (p < .001) and anger (p = .036). Finally, CLV of bilateral amygdala was a significant predictor of RME (p < .001) and FAR (p = .005). CONCLUSION: We conclude that SC can be impaired in several domains in RRMS patients even in the absence of CI and that it is related specifically to bilateral amygdala damage as measured by CLV.

Spatial grounding of symbolic arithmetic: an investigation with optokinetic stimulation.

Growing evidence suggests that mental calculation might involve movements of attention along a spatial representation of numerical magnitude. Addition and subtraction on nonsymbolic numbers (numerosities) seem to induce a "momentum" effect, and have been linked to distinct patterns of neural activity in cortical regions subserving attention and eye movements. We investigated whether mental arithmetic on symbolic numbers, a cornerstone of abstract mathematical reasoning, can be affected by the manipulation of overt spatial attention induced by optokinetic stimulation (OKS). Participants performed additions or subtractions of auditory two-digit numbers during horizontal (experiment 1) or vertical OKS (experiment 2), and eye movements were concurrently recorded. In both experiments, the results of addition problems were underestimated, whereas results of subtractions were overestimated (a pattern that is opposite to the classic Operational Momentum effect). While this tendency was unaffected by OKS, vertical OKS modulated the occurrence of decade errors during subtractions (i.e., fewer during downward OKS and more frequent during upward OKS). Eye movements, on top of the classic effect induced by OKS, were affected by the type of operation during the calculation phase, with subtraction consistently leading to a downward shift of gaze position and addition leading to an upward shift. These results highlight the pervasive nature of spatial processing in mental arithmetic. Furthermore, the preeminent effect of vertical OKS is in line with the hypothesis that the vertical dimension of space-number associations is grounded in universal (physical) constraints and, thereby, more robust than situated and culture-dependent associations with the horizontal dimension.

Conventional and functional assessment of spatial neglect: Clinical practice suggestions.

OBJECTIVE: Spatial neglect (SN) constitutes a substantial barrier to functional recovery after acquired brain injury. However, because of its multimodal nature, no single test can capture all the signs of SN. To provide a clinically feasible solution, we used conventional neuropsychological tests as well as the Catherine Bergego Scale (CBS) via the Kessler Foundation Neglect Assessment Process (KF-NAP). The goal was to add evidence that a global approach should detect better even subtle signs of SN. METHOD: Fourteen individuals with lesions located in the right cerebral hemisphere participated in the study. Participants were assessed with a comprehensive battery of neuropsychological tests, comprising a set of visuospatial tests to evaluate several spatial domains. In addition, patients underwent functional assessment with the Barthel Index, the Functional Independence Measure (FIM), and the CBS via KF-NAP. RESULTS: The CBS via KF-NAP was associated with the visuospatial paper-based tests (p = .004) as well as the Motor FIM (p = .003), and was more sensitive than the Behavioral Inattention Test-Conventional in detecting SN (p = .014). CONCLUSIONS: We showed that the CBS via KF-NAP was able: (a) to detect functional impairment, especially motor, related to SN; (b) to selectively measures spatial rather than nonspatial dysfunctions; and (c) to be highly sensitive in detecting SN signs especially in those patients with mild severity, covering several aspects of SN manifestations. The patient's SN diagnosis based on the CBS via KF-NAP is clinically important and directly relevant to care planning and goal setting. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

The effect of fingolimod on focal and diffuse grey matter damage in active MS patients.

INTRODUCTION: The mechanism of action of fingolimod within the central nervous system and its efficacy in reducing/preventing both focal and diffuse grey matter (GM) damage in active multiple sclerosis (MS) are not completely understood. METHODS: In this longitudinal, 2-year prospective, phase IV, single-blind study, 40 MS patients treated with fingolimod and 39 untreated age, gender, and disability-matched MS patients were enrolled. Each patient underwent a neurological examination every 6 months and a 3T MRI at the beginning of the treatment and after 24 months. The accumulation of new cortical lesions (CLs) and the progression of regional GM atrophy were compared between the two groups. RESULTS: At the end of the study (T24), the percentage of patients with new CLs (13.5 vs. 89%, p < 0.001) and the percentage of GM volume change was lower in the treated group (p < 0.001). The regional analysis revealed that the treated group had also less volume loss in thalamus, caudatus, globus pallidus, cingulate cortex, and hippocampus (p < 0.001), as well as in, cerebellum, superior frontal gyrus, and insular-long gyrus (p < 0.05). Patients with no evidence of disease activity were 60% in the treated group and 10% in the untreated group (p < 0.001). CONCLUSIONS: These results suggest a possible protective effect of fingolimod on focal and diffuse GM damage.