Characterization of social cognition impairment in multiple sclerosis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) has been associated with deficits in social cognition. However, little is known about which domains of social cognition are predominantly affected and what other factors are associated with it. The aim was (i) to characterize social cognition deficit in a group of MS outpatients and (ii) to relate impairment in social cognition to overall cognitive status, depression and fatigue. METHODS: Thirty-five MS patients (mean disease duration 12.9 years, median Expanded Disability Status Scale (EDSS) 3 and 34 healthy controls (HCs) were examined using the German version of the Geneva Social Cognition Scale to measure different domains of social cognition. Standard neuropsychological testing was applied to all patients and to 20 HCs. Patient-reported outcomes included questionnaires for fatigue, depression, anxiety and executive-behavioural disturbances. RESULTS: The mean social cognition raw score was lower in the MS patients compared to the HCs (86.5 ± 8.7 vs. 91.2 ± 5.9, P = 0.005; d = 0.6) and did not correlate with EDSS or disease duration. The difference was driven by facial affect recognition and the understanding of complex social situations (14% and 23% of patients respectively under the cut-off). The impairment in these two tasks did not correlate with general cognitive performance or depression but with fatigue. CONCLUSIONS: The impairment in our group was restricted to high order and affective social cognition tasks and independent of general cognitive performance, EDSS, disease duration and depression. Fatigue correlated with social cognition performance, which might be due to common underlying neuronal networks.

Age-Related Differences in Cortical and Subcortical Activities during Observation and Motor Imagery of Dynamic Postural Tasks: An fMRI Study.

Age-related changes in brain activation other than in the primary motor cortex are not well known with respect to dynamic balance control. Therefore, the current study aimed to explore age-related differences in the control of static and dynamic postural tasks using fMRI during mental simulation of balance tasks. For this purpose, 16 elderly (72 ± 5 years) and 16 young adults (27 ± 5 years) were asked to mentally simulate a static and a dynamic balance task by motor imagery (MI), action observation (AO), or the combination of AO and MI (AO + MI). Age-related differences were detected in the form of larger brain activations in elderly compared to young participants, especially in the challenging dynamic task when applying AO + MI. Interestingly, when MI (no visual input) was contrasted to AO (visual input), elderly participants revealed deactivation of subcortical areas. The finding that the elderly demonstrated overactivation in mostly cortical areas in challenging postural conditions with visual input (AO + MI and AO) but deactivation in subcortical areas during MI (no vision) may indicate that elderly individuals allocate more cortical resources to the internal representation of dynamic postural tasks. Furthermore, it might be assumed that they depend more strongly on visual input to activate subcortical internal representations.

Feasibility and initial efficacy of a cognitive-behavioural group programme for managing anger and aggressiveness after traumatic brain injury.

This study assesses the feasibility of a cognitive-behavioural group programme for treating anger and aggressiveness after a traumatic brain injury (TBI). Five feasibility criteria were considered: demand, implementation, practicality, acceptability and initial efficacy. A self-report questionnaire of aggressiveness (AQ-12) was administered before the intervention (T1), one week following the intervention (T2) and at a four months follow-up (T3). Ten patients with moderate to severe chronic TBI completed the programme through eight once-a-week sessions. The analysis of the feasibility outcomes suggests that: (1) The recruitment, the process of grouping participants and the characterisation of anger and aggressiveness at baseline need to be re-evaluated and improved for future designs. (2) The use of specific strategies for bypassing cognitive and other behavioural dysfunctions related to TBI is crucial for the success of this intervention and merits special attention. (3) The high retention rate, the convenient meeting schedule, cost advantages and the good acceptability by participants are positive arguments for the implementation of a larger trial. (4) The significant reduction of AQ-12 scores at T3 and the high effect size constitute a change in the expected direction and support the initial efficacy of the programme.

Embodiment of action-related language in the native and a late foreign language - An fMRI-study.

Theories of embodied cognition postulate that language processing activates similar sensory-motor structures as when interacting with the environment. Only little is known about the neural substrate of embodiment in a foreign language (L2) as compared to the mother tongue (L1). In this fMRI study, we investigated embodiment of motor and non-motor action verbs in L1 and L2 including 31 late bilinguals. Half had German as L1 and French as L2, and the other half vice-versa. We collapsed across languages to avoid the confound between language and order of language acquisition. Region of interest analyses showed stronger activation in motor regions during L2 than during L1 processing, independently of the motor-relatedness of the verbs. Moreover, a stronger involvement of motor regions for motor-related as compared to non-motor-related verbs, similarly for L1 and L2, was found. Overall, the similarity between L1 and L2 embodiment seems to depend on individual and contextual factors.

Current exposure to a second language modulates bilingual visual word recognition: An EEG study.

Bilingual word recognition has been the focus of much empirical work, but research on potential modulating factors, such as individual differences in L2 exposure, are limited. This study represents a first attempt to determine the impact of L2-exposure on bilingual word recognition in both languages. To this end, highly fluent bilinguals were split into two groups according to their L2-exposure, and performed a semantic categorisation task while recording their behavioural responses and electro-cortical (EEG) signal. We predicted that lower L2-exposure should produce less efficient L2 word recognition processing at the behavioural level, alongside neurophysiological changes at the early pre-lexical and lexical levels, but not at a post-lexical level. Results confirmed this hypothesis in accuracy and in the N1 component of the EEG signal. Precisely, bilinguals with lower L2-exposure appeared less accurate in determining semantic relatedness when target words were presented in L2, but this condition posed no such problem for bilinguals with higher L2-exposure. Moreover, L2-exposure modulates early processes of word recognition not only in L2 but also in L1 brain activity, thus challenging a fully non-selective access account (cf. BIA + model, Dijkstra and van Heuven, 2002). We interpret our findings with reference to the frequency-lag hypothesis (Gollan et al., 2011).

[Return to work after brain lesions: cognitive and behavioral factors]. / Troubles cognitifs et comporte mentaux après lésion cérébrale: impact sur la reprise professionnelle.

Complete or partial return to work (RTW) succeeds in around 40% of TBI and 25% of stroke patients. Positive factors include: (1) post-traumatic amnesia, hospitalization length, age, race, pretraumatic work and socio-educational status, quality of life, (2) premorbid intellectual level, learning, language and attentional, (3) social cognition and deficit's awareness and (4) absence of behavioural impairment. In stroke, RTW is associated with normal neurological and cognitive/communication abilities. Vocational rehabilitation necessitates: (1) cognitive retraining (speed, visuospatial skills and memory), (2) behavioural approach (compensation, organization, abstraction) and (3) adaptation of work profile. Case management models, with early intervention, continuity of care and coordination, increase twofold partial or complete adapted RTW.

[Neurobehavioral changes occurring during multiple sclerosis]. / Modifications neurocomportementales secondaires à la sclérose en plaques.

Behavioral changes occurring in patients affected by multiple sclerosis (MSI are often neglected by physicians but are actually part of the clinical spectrum of the disease. In addition, they are known to be responsible for a decline in the quality of life of MS patients. Recently, there has been a growing interest to investigate changes in the emotional experience of MS patients and their decision making, showing that the ability to take advantageous decisions was altered in MS. This paper reviews existing data on this topic.

[New spectrum of HIV-associated cognitive disorders in the HAART era]. / Nouveau spectre des troubles cognitifs liés à l'infection par le VIH à l'ère des trithérapies.

Highly active anti-retroviral therapy (HAART) has almost abolished HIV-related mortality and serious opportunistic diseases; among them, AIDS-related dementia. However, minor forms of cognitive dysfunction, have not disappeared, and even increased in frequency. Ageing of HIV+ patients, insufficient penetration of anti-viral drugs into the brain with continuous low-grade viral production and inflammation may play a role. Minor cognitive dysfunction in HIV infection shares some clinical and pathophysiological features with neuro-degenerative diseases, in particular Alzheimers disease. It can thus be postulated that, such in Alzheimer disease, anti-cholinesterase drugs might also be efficacious in AIDS-related minor cognitive dysfunction. This hypothesis has not been tested yet however A clinical trial using ravistigmine is starting this spring in patients with HIV-associated cognitive dysfunction in Geneva and Lausanne.

Preserved decision making ability in early multiple sclerosis.

BACKGROUND: The purpose of this study was to assess decision making in patients with multiple sclerosis (MS) at the earliest clinically detectable time point of the disease. METHODS: Patients with definite MS (n = 109) or with clinically isolated syndrome (CIS, n = 56), a disease duration of 3 months to 5 years, and no or only minor neurological impairment (Expanded Disability Status Scale [EDSS] score 0-2.5) were compared to 50 healthy controls using the Iowa Gambling Task (IGT). RESULTS: The performance of definite MS, CIS patients, and controls was comparable for the two main outcomes of the IGT (learning index: p = 0.7; total score: p = 0.6). The IGT learning index was influenced by the educational level and the co-occurrence of minor depression. CIS and MS patients developing a relapse during an observation period of 15 months dated from IGT testing demonstrated a lower learning index in the IGT than patients who had no exacerbation (p = 0.02). When controlling for age, gender and education, the difference between relapsing and non-relapsing patients was at the limit of significance (p = 0.06). CONCLUSION: Decision making in a task mimicking real life decisions is generally preserved in early MS patients as compared to controls. A possible consequence of MS relapsing activity in the impairment of decision making ability is also suspected in the early phase of MS.

[Neuropsychiatry of epilepsy, stroke, Parkinson's disease and multiple sclerosis]. / Neuropsychiatrie de l'épilepsie, des accidents vasculaires cérébraux, de la maladie de Parkinson et de la sclérose en plaques.

The assessement of behavior is common part of the neurological examination. This article reviews the behavioral and mood manifestations in four classical syndroms: Epilepsy, stroke, Parkinson's disease and multiple sclerosis.

Auditory time perception in Huntington's disease.

BACKGROUND: Huntington's disease (HD) is characterized by early involvement of the striatum. It affects the pace of repetitive motor activity, as motor timing depends on basal ganglia activity. However, data are lacking on the impact of this process on auditory time perception in motor non-affected gene carriers. OBJECTIVE: This work aims to test the performance in time perception of a group of mutation carriers, either without motor symptoms or at an early stage of motor involvement. This should allow designing therapies targeting compensation strategies and possibly be used as a disease progression marker. METHOD: Time was assessed using two different tasks. An absolute, duration-based time perception was assessed in a first task and a relative, beat-based time perception was assessed in a second one. HD-mutation carriers with low-to-middle grades of motor involvement (HD-motor, n = 10) or without motor signs (HD-premotor n = 21), were compared with age- and sex-matched healthy controls (control (n = 27)). Thresholds of time difference perception where assessed. RESULTS: For both tasks, poorer performances were found in HD-motor patients as compared with HD-premotor and controls. Thresholds of time difference perception correlated positively with the CAP score for the whole group of HD-gene carriers in both tasks. In a post-hoc exploratory analysis performed by a multiple regression, a negative correlation was found between the thresholds in both tasks and the Stroop interference test. Furthermore, in the first task, a positive correlation was found between thresholds and a trail making B test and a negative one with a total functional score. CONCLUSION: Our data confirm that the impairment in time perception in persons affected by HD correlates with the advancing disease. They also suggest that time perception depends on similar cognitive mechanisms as the ones sub-serving the Stroop interference test.

Cognition, mood and fatigue in patients in the early stage of multiple sclerosis.

QUESTION UNDER STUDY: Cognitive impairment occurs during multiple sclerosis (MS) and contributes to the burden of the disease, but its effect in the initial phase of MS still needs to be better understood. METHODS: We prospectively studied 127 early MS patients presenting with a clinically isolated syndrome (CIS) or definite MS, a mean disease duration of 2.6 years, and with minor disability (mean Expanded Disability Status Scale score 1.8). Patients were tested for long-term memory, executive functions, attention, fatigue, mood disorders, functional handicap and quality of life (QoL). Twenty-one CIS patients were excluded from study as the diagnosis of MS could not be confirmed. RESULTS: Over the 106 MS patients analysed, 31 (29.3%) were cognitively impaired (23.6% for memory, 10.4% for attention and 5.7% for executive functions). Cognitive deficits were already present in CIS patients in whom the diagnosis was not yet confirmed (20%). Impaired cognition was associated with anxiety (p = 0.05), depression(p = 0.004), fatigue (p = 0.03), handicap (p <0.001) and a lower QoL (p <0.001). After adjustment for QoL, handicap, depression, anxiety and fatigue were no longer associated with the presence of cognitive deficits. CONCLUSIONS: In this well-defined early MS group one third of the patients already exhibited cognitive deficits, which were usually apparent in an effortful learning situation and were generally mild. Mood disorders, fatigue, handicap and decreased QoL were all associated with the occurrence of cognitive deficits. QoL itself appeared to take all the other factors into account. Our results confirm the existence of an interplay between cognitive, affective and functional changes and fatigue in early MS.

[Fatigue in neurological disease: different patterns in stroke and multiple sclerosis]. / Dimensions multiples de la fatigue d'origine neurologique: différences entre l'accident vasculaire cérébral et la sclérose en plaques.

INTRODUCTION: Fatigue is a complex, subjective experience, frequent in multiple sclerosis (MS) and stroke patients. The tiredness these patients experience can take on many features depending not only on the cerebral location of the lesions and mood aspects, but also on the pathophysiology of the disease. Thus, it is reasonable to expect that fatigue may have different implications in MS and stroke. The aim of the present work was to compare fatigue syndrome in these two populations. Patients were matched for handicap. MATERIALS AND METHODS: Seventy-nine stroke and 39 MS outpatients were included with the following inclusion criteria: i) patients with possible or relapsing-remitting MS with an Expanded Disability Status Scale (EDSS) score<2.5, disease duration<6 years, and stable medical condition for at least 6 weeks; ii) stroke patients with mild neurological impairment, i.e. scoring<3 at the National Institute of Health Stroke Scale (NIHSS) one year after stroke; iii) absence of functional impairment (Barthel index=100) and similar negligible handicap (Rankin scale<2 for both groups); no or mild cognitive deficit; iv) neither DSMIV criteria of depression, nor significant anxious/depressive symptoms (Hospital Anxiety and Depression scale; HAD; score<8) in both groups. The Fatigue Assessing Instrument (FAI) was used to assess fatigue. RESULTS: Twenty-nine percent of stroke and 46 p. cent of MS patients had a significant score on the FAI (p<0.05). Multiple regression analysis using groups, gender and age as factors showed a group effect in 3 out of 4 subscales: MS patients scored higher than stroke patients mainly for psychic impact (4.86 vs. 3.28), but also for severity (mean 3.86 vs. 2.97) and specificity (4.36 vs. 3.32). Response to rest (5.36 vs. 6.06) only tended to be better in the stroke group. In the subpopulation with significant fatigue scores, psychic impact was more elevated in the MS group. The functional consequence of fatigue in physical, professional and social activities were similar. DISCUSSION: Fatigue was more severe in MS than stroke patients, independently of disability. The most significant factor in the MS group was the psychic impact, reflecting impaired motivation, concentration and irritability, despite the absence of depression. However, subjective consequences of fatigue on work, family and leisure activities were comparable in both groups.

Successful neuropsychological rehabilitation in a patient with Cerebellar Cognitive Affective Syndrome.

The objective of this case study was to describe the neuropsychological rehabilitation of a 16-year-old patient who presented a Cerebellar Cognitive Affective Syndrome (CCAS) following a bilateral cerebellar hemorrhage. The patient presented severe and diffuse cognitive deficits, massive behavioral disorders, and emotion regulation difficulties. The cognitive rehabilitation was performed in the chronic phase (one year after the onset of the hemorrhage) using a transdisciplinary neurobehavioral approach based on the patient's favorite interest (soccer). A significant behavioral and cognitive improvement was observed. The patient became progressively independent in all activities of daily living and was discharged home. The Functional Independence Measure at discharge was 124/126 (vs. 37/126 at entry). The patient was able to complete his schooling despite the mild cognitive and behavioral sequelae. This first description of the use of neurobehavioral therapy in a case of chronic CCAS suggests that (a) major clinical improvement can occur more than one year after the onset of the CCAS, showing the importance of long-term and intensive neurorehabilitation; and (b) when the cerebellum cannot properly play its regulator role in cognition, neuropsychological intervention through a behavioral and cognitive approach can be of great help by acting as an external modulator to help the patient regain control over himself.

[Neurodegeneration and cerebrovascular disease: causal or incidental link?]. / Neurodégénerescence et maladies cérébrovasculaires: coïncidence ou causalité?

Neurodegenerative and cerebrovascular diseases have been related for more than a century. Epidemiological data show that main vascular risk factors are also risk factors for Alzheimer disease. Experimental evidences demonstrate that some of those risk factors accelerate the progress of Alzheimer lesions, mainly by acting on the amyloid cascade. Recent advances in understanding the basic mechanisms of CADASIL and familial amyloid angiopathy reveal that these forms of vascular dementias are degenerative disease of brain vessels. Modern neuroimaging techniques will allow to better understand relations between symptomatic strokes, silent infarcts, leukoaraiosis, microbleeds and degenerative pathology before the stage of dementia.

Screening for Language Disorders in Stroke: German Validation of the Language Screening Test (LAST).

BACKGROUND: Screening of aphasia in acute stroke is crucial for directing patients to early language therapy. The Language Screening Test (LAST), originally developed in French, is a validated language screening test that allows detection of a language deficit within a few minutes. The aim of the present study was to develop and validate two parallel German versions of the LAST. METHODS: The LAST includes subtests for naming, repetition, automatic speech, and comprehension. For the translation into German, task constructs and psycholinguistic criteria for item selection were identical to the French LAST. A cohort of 101 stroke patients were tested, all of whom were native German speakers. Validation of the LAST was based on (1) analysis of equivalence of the German versions, which was established by administering both versions successively in a subset of patients, (2) internal validity by means of internal consistency analysis, and (3) external validity by comparison with the short version of the Token Test in another subset of patients. RESULTS: The two German versions were equivalent as demonstrated by a high intraclass correlation coefficient of 0.91. Furthermore, an acceptable internal structure of the LAST was found (Cronbach's α = 0.74). A highly significant correlation (r = 0.74, p < 0.0001) between the LAST and the short version of the Token Test indicated good external validity of the scale. CONCLUSION: The German version of the LAST, available in two parallel versions, is a new and valid language screening test in stroke.

Lack of anticipatory gaze-orienting responses in patients with right brain damage.

OBJECTIVE: To study eye movements during cervical proprioceptive stimulation by passive body rotation in darkness, with the head held stationary, in patients with right brain damage and hemineglect. BACKGROUND: At very low frequency, this stimulation is reported to produce an illusion of head turning in space and eye deviations directed opposite to trunk rotation (in the direction of the illusory head rotation). METHODS: Ten normal subjects and seven patients with unilateral cerebral lesions (five right brain-damaged patients with mild to moderate visuospatial neglect, two left brain-damaged patients without neglect) were included in the study. Subjects were seated on a rotating chair. Stimuli consisted of slow sinusoidal passive trunk rotations (+/-30 degrees, 0.01 Hz) while the head was fixed in space. RESULTS: Eye movements directed opposite to trunk rotation were typical for normal subjects and for left brain-damaged patients. In contrast, all right brain-damaged patients showed either eye movements in the direction of trunk rotation or no eye deviations at all. CONCLUSION: This result could characterize a lack of anticipatory coordinating gaze behavior in patients with right brain damage.

(133)Xe SPECT cerebral blood flow study in a healthy population: determination of T-scores.

UNLABELLED: Dementia is becoming a major health problem as the population of the Northern Hemisphere ages. Early differential diagnosis between normal cognitive decline and dementia is particularly difficult. If psychometric evaluation can contribute to the diagnosis, quantitative cerebral functional imaging would play an important role. We therefore proposed, first, to constitute a normative dataset that could later be used to identify subjects at risk for neurodegenerative processes and, second, to describe the risk of abnormal global cerebral blood flow (gCBF) by defining categories based on the standardized cutoff scores of a young, healthy population (T-score). METHODS: Of a total of 203 healthy volunteers, 187 were included in the protocol, which included evaluation of medical history, neurologic and neuropsychologic status, and body composition; analysis of blood; and measurement of gCBF by means of (133)Xe SPECT. RESULTS: With ANOVA analysis using age and sex as between-subject factors and gCBF as a within-subject factor, a significantly higher gCBF was found in women than in men. In addition, a linear reduction as a function of age was observed for both sexes (-0.3%/y). T-score was determined for the 18- to 28-y-old age group, for whom gCBF was found to be 46.7 +/- 5.1 mL/min/100 g tissue in men and 49.0 +/- 5.0 mL/min/100 g tissue in women. The age-dependent decrease could thus be expressed in T-scores and, in the 29- to 38-y-old, 39- to 48-y-old, and >48-y-old age groups, averaged -0.63, -1.29, and -1.92, respectively, in men and -0.63, -0.83, and-2.40, respectively, in women. Cognitive performance, body composition, and blood analysis revealed the expected significant effects from sex and age. CONCLUSION: The large-scale reference database of gCBF measurements constituted from a healthy, well-controlled population enabled age and sex stratification, which showed significant differences between the sexes and a significant decline as a function of age. T-scores were determined and warrant further studies on the prospective identification of early dementia by (133)Xe SPECT in elderly individuals.

The time course of semantic category processing in the cerebral hemispheres: an electrophysiological study.

Using visual half-field presentations of words to the right (RVF) and to the left visual field (LVF), this study investigated the time course of the hemispheric involvement in the processing of semantic category information. Multi-channel event related brain potentials (ERPs) were recorded from 15 healthy subjects during a categorisation task of sequentially presented word pairs. Subjects had to judge mentally after the appearance of the second word whether the words of a pair were semantically related (SR) or not (SU). ERPs were computed, from 100 ms before the onset of the second word to 600 ms, for SR and SU conditions in the LVF and in the RVF separately. The temporal segmentation of ERP map series into sequences of quasi-stable map configurations revealed a total of seven segments in each visual field of which only the first five (S1-S5, appearing between 70 and 400 ms) showed different map configurations as a function of visual field but presented a similar temporal sequence in both visual fields. By contrast, of the last two segments (S6 and S7) which appeared between approximately 400 and approximately 600 ms, only S7 differentiated SR and SU conditions in terms of its duration. Source localisation analysis of the segments showed that following the initial activation of posterior brain regions as a function of the visual field of presentation, a common neural network was activated in the left hemisphere (LH) although the dynamics of activation varied as a function of visual field. Concerning the role of the right hemisphere (RH) in lexico-semantic processing, the results presented here appear to be compatible with a 'callosal relay model' and suggest that, in healthy subjects, information is transferred rapidly ( approximately 150 ms) from the RH to the language dominant-LH.

Language representation in a patient with a dominant right hemisphere: fMRI evidence for an intrahemispheric reorganisation.

Studies have suggested that congenital left hemispheric (LH) frontal arteriovenous malformations (AVMs) are associated with an early transfer of language to right hemisphere (RH) frontal regions. The question remains whether such anatomofunctional reorganisation is due to RH compensatory abilities or to a general principle of lateral shift. In this study, we used fMRI language paradigms to investigate the case of a patient presenting aphasic symptoms following an haemorrhage due to a right frontal AVM. Prior to surgery, fMRI showed that language processing was confined to the RH, suggesting that language had not shifted during childhood from this congenitally dominant RH to the LH. After surgery, the patient presented severe aphasia that recovered to presurgical level within 70 days. At this time, fMRI showed that language tasks were still not associated with activations in the LH. These results suggest that the principles of early cerebral reorganisation after congenital lesions may differ in the RH and the LH. In addition, they support the idea that efficient restoration of language is achieved if a sufficiently large neuronal network is preserved around the lesion.