Joint impact on attention, alertness and inhibition of lesions at a frontal white matter crossroad.

In everyday life, information from different cognitive domains-such as visuospatial attention, alertness and inhibition-needs to be integrated between different brain regions. Early models suggested that completely segregated brain networks control these three cognitive domains. However, more recent accounts, mainly based on neuroimaging data in healthy participants, indicate that different tasks lead to specific patterns of activation within the same, higher-order and 'multiple-demand' network. If so, then a lesion to critical substrates of this common network should determine a concomitant impairment in all three cognitive domains. The aim of the present study was to critically investigate this hypothesis, i.e. to identify focal stroke lesions within the network that can concomitantly affect visuospatial attention, alertness and inhibition. We studied an unselected sample of 60 first-ever right-hemispheric, subacute stroke patients using a data-driven, bottom-up approach. Patients performed 12 standardized neuropsychological and oculomotor tests, four per cognitive domain. A principal component analysis revealed a strong relationship between all three cognitive domains: 10 of 12 tests loaded on a first, common component. Analysis of the neuroanatomical lesion correlates using different approaches (i.e. voxel-based and tractwise lesion-symptom mapping, disconnectome maps) provided convergent evidence on the association between severe impairment of this common component and lesions at the intersection of superior longitudinal fasciculus II and III, frontal aslant tract and, to a lesser extent, the putamen and inferior fronto-occipital fasciculus. Moreover, patients with a lesion involving this region were significantly more impaired in daily living cognition, which provides an ecological validation of our results. A probabilistic functional atlas of the multiple-demand network was performed to confirm the potential relationship between patients' lesion substrates and observed cognitive impairments as a function of the multiple-demand network connectivity disruption. These findings show, for the first time, that a lesion to a specific white matter crossroad can determine a concurrent breakdown in all three considered cognitive domains. Our results support the multiple-demand network model, proposing that different cognitive operations depend on specific collaborators and their interaction, within the same underlying neural network. Our findings also extend this hypothesis by showing (i) the contribution of superior longitudinal fasciculus and frontal aslant tract to the multiple-demand network; and (ii) a critical neuroanatomical intersection, crossed by a vast amount of long-range white matter tracts, many of which interconnect cortical areas of the multiple-demand network. The vulnerability of this crossroad to stroke has specific cognitive and clinical consequences; this has the potential to influence future rehabilitative approaches.

Improved gesturing in left-hemispheric stroke by right inferior parietal theta burst stimulation.

Objectives: Apraxia is a common syndrome of left hemispheric stroke. A parieto-premotor-prefrontal network has been associated with apraxia, in which the left inferior parietal lobe (IPL-L) plays a major role. We hypothesized that transcranial continuous theta burst stimulation (cTBS) over the right inferior parietal lobe (IPL-R) improves gesturing by reducing its inhibition on the contralateral IPL in left hemispheric stroke patients. It was assumed that this effect is independent of lesion volume and that transcallosal connectivity is predictive for gestural effect after stimulation. Materials and methods: Nineteen stroke patients were recruited. Lesion volume and fractional anisotropy of the corpus callosum were acquired with structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Each patient had pseudorandomised sessions with sham or with stimulation over the IPL-R or over the right inferior frontal gyrus IFG-R. Gesturing was assessed in a double-blinded manner before and after each session. We tested the effects of stimulation on gesture performance using a linear mixed-effects model. Results: Pairwise treatment contrasts showed, that, compared to sham, the behavioral effect was higher after stimulation over IPL-R (12.08, 95% CI 6.04 - 18.13, p < 0.001). This treatment effect was approximately twice as high as the contrasts for IFG-R vs. sham (6.25, 95% CI -0.20 - 12.70, p = 0.058) and IPL-R vs. IFG-R vs. sham (5.83, 95% CI -0.49 - 12.15, p = 0.071). Furthermore, higher fractional anisotropy in the splenium (connecting the left and right IPL) were associated with higher behavioral effect. Relative lesion volume did not affect the changes after sham or stimulation over IPL-R or IFG-R. Conclusion: One single session of cTBS over the IPL-R improved gesturing after left hemispheric stroke. Denser microstructure in the corpus callosum correlated with favorable gestural response. We therefore propose the indirect transcallosal modulation of the IPL-L as a promising model of restoring interhemispheric balance, which may be useful in rehabilitation of apraxia.

Fitness-to-drive for glioblastoma patients: Guidance from the Swiss Neuro-Oncology Society (SwissNOS) and the Swiss Society for Legal Medicine (SGRM).

OBJECTIVE: The management of brain tumour patients who would like to resume driving is complex, and needs multidisciplinary input and a consensus among treating physicians. The Swiss Neuro-Oncology Society (SwissNOS) and the Swiss Society for Legal Medicine (SGRM) aim to provide guidance on how to assess "fitness-to-drive" of glioblastoma patients and to harmonise the relevant procedures in Switzerland. METHODS: At several meetings, Swiss neuro-oncologists discussed common practices on how to advise patients with a stable, i.e., non-progressive, glioblastoma, who wish to resume driving after the initial standard tumour treatment. All participants of the SwissNOS meetings were invited twice to return a questionnaire (modified Delphi process) on specific tools/procedures they commonly use to assess "fitness-to-drive" of their patients. Answers were analysed to formulate a tentative consensus for a structured and reasonable approach. RESULTS: Consensus on minimum requirements for a "fitness-to-drive" programme for glioblastoma patients could be reached among Swiss neuro-oncologists. The recommendations were based on existing guidelines and expert opinions regarding patients with seizures, visual disturbances, cognitive impairment or focal deficits for safe driving. At this point in time, the Swiss neuro-oncologists agreed on the following requirements for glioblastoma patients after the initial standard therapy and without a seizure for at least 12 months: (1) stable cranial magnetic resonance imaging (MRI) according to Response Assessment in Neuro-Oncology (RANO) criteria, to be repeated every 3 months; (2) thorough medical history, including current or new medication, a comprehensive neurological examination at baseline (T0) and every 3 months thereafter, optionally an electrocencephalogram (EEG) at baseline; (3) ophthalmological examination including visual acuity and intact visual fields; and (4) optional neuropsychological assessment with a focus on safe driving. Test results have to be compatible with safe driving at any time-point. Patients should be informed about test results and optionally sign a document. CONCLUSIONS: We propose regular thorough clinical neurological examination and brain MRI, optional EEG, neuropsychological and visual assessments to confirm "fitness-to-drive" for glioblastoma patients after initial tumour-directed therapy. The proposed "fitness-to-drive" assessments for glioblastoma patients serves as the basis for a prospective Swiss Pilot Project GLIODRIVE (BASEC ProjectID 2020-00365) to test feasibility, adherence and safety in a structured manner for patients who wish to resume driving. Research will focus on confirming the usefulness of the proposed tools in predicting "fitness-to-drive" and match results with events obtained from the road traffic registry (Strassenverkehrsamt).

Can I Discharge My Stroke Patient Home After Inpatient Neurorehabilitation? LIMOS Cut-Off Scores for Stroke Patients "Living Alone" and "Living With Family".

Background: Discharge planning of stroke patients during inpatient neurorehabilitation is often difficult since it depends both on the patient's ability to perform activities of daily living (ADL) and the social context. The aim of this study was to define ADL cut-off scores using the Lucerne ICF-based multidisciplinary observation scale (LIMOS) that allow the clinicians to decide whether stroke patients who "live alone" and "live with a family" can be discharged home or must enter a nursing home. Additionally, we investigated whether age and gender factors influence these cut-off scores. Methods: A single-center retrospective cohort study was conducted to establish cut-off discharge scores for the LIMOS. Receiver-operating-characteristics curves were calculated for both patient groups "living alone" and "living with family" to illustrate the prognostic potential of the LIMOS total score with respect to their discharge goals (home alone or nursing home; home with family or nursing home). A logistic regression model was used to determine the (age- and gender-adjusted) odds ratios of being released home if the LIMOS total score was above the cut-off. A single-center prospective cohort study was then conducted to verify the adequacy of the cut-off values for the LIMOS total score. Results: A total of 687 stroke inpatients were included in both studies. For the group "living alone" a LIMOS total score above 158 indicated good diagnostic accuracy in predicting discharge home (sensitivity 93.6%; specificity 95.4%). A LIMOS total cut-off score above 130 points was found for the group "living with family" (sensitivity 92.0%; specificity 88.6%). The LIMOS total score odds ratios, adjusted for age and gender, were 292.5 [95% CI: (52.0-1645.5)] for the group "living alone" and were 89.4 [95% CI: (32.3-247.7)] for the group "living with family." Conclusion: Stroke survivors living alone needed a higher ADL level to return home than those living with a family. A LIMOS total score above 158 points allows a clinician to discharge a patient that lives alone, whereas a lower LIMOS score above 130 points can be sufficient in a patient that lives with a family. Neither age nor gender played a significant role.

The right anterior temporal lobe critically contributes to magnitude knowledge.

Cognitive estimation is a mental ability applied to solve numerical problems when precise facts are unknown, unavailable or impractical to calculate. It has been associated with several underlying cognitive components, most often with executive functions and semantic memory. Little is known about the neural correlates of cognitive estimation. To address this issue, the present cross-sectional study applied lesion-symptom mapping in a group of 55 patients with left hemineglect due to right-hemisphere stroke. Previous evidence suggests a high prevalence of cognitive estimation impairment in these patients, as they might show a general bias towards large magnitudes. Compared to 55 age- and gender-matched healthy controls, the patient group demonstrated impaired cognitive estimation. However, the expected large magnitude bias was not found. Lesion-symptom mapping related their general estimation impairment predominantly to brain damage in the right anterior temporal lobe. Also critically involved were the right uncinate fasciculus, the anterior commissure and the right inferior frontal gyrus. The main findings of this study emphasize the role of semantic memory in cognitive estimation, with reference to a growing body of neuroscientific literature postulating a transmodal hub for semantic cognition situated in the bilateral anterior temporal lobe. That such semantic hub function may also apply to numerical knowledge is not undisputed. We here propose a critical contribution of the right anterior temporal lobe to at least one aspect of number processing, i.e. the knowledge about real-world numerical magnitudes.

Eyetracking during free visual exploration detects neglect more reliably than paper-pencil tests.

Neglect after stroke is most accurately diagnosed by a systematic, ecological observation during everyday behaviour using the Catherine Bergego Scale (CBS). However, the CBS is time-consuming and often omitted in clinical settings, especially stroke units. In this study, we aimed to explore if video-oculography during free visual exploration (FVE), which can be performed in few minutes, is sensitive in mirroring neglect in everyday behaviour and whether it is more sensitive than conventional neuropsychological paper-pencil tests. In this retrospective, observational, multicentre study, we identified 78 patients in our database with subacute right-hemispheric stroke, with and without neglect in everyday behaviour, diagnosed by the CBS, who also performed FVE. 40 age-matched healthy participants served as controls. The sensitivity to detect neglect was compared between FVE (i.e., mean gaze position on the horizontal axis) and conventional neuropsychological paper-pencil tests, i.e., Random Shape Cancellation, Line Bisection, Two-Part Picture, Bells, Star Cancellation, Letter Cancellation, Sensitive Neglect, and Five-Point. FVE correctly identified neglect in 85%of patients, with an AUC-value of .922 in ROC-analysis. Conventional neuropsychological paper-pencil tests, considered alone or in combination, showed heterogeneous results, and identified neglect significantly less often (21.74%-68.75%). Moreover, there was a significant correlation between mean gaze position and CBS scores, providing evidence for the relationship between FVE and neglect in everyday behaviour. Furthermore, VLSM analyses suggested that the absence of a pathological rightward bias in FVE might depend on the integrity of the second branch of the right Superior Longitudinal Fascicle (SLF II), a white-matter tract connecting cortical areas critical for visual attention. Video-oculography during FVE has a high sensitivity and specificity to diagnose neglect after stroke and it is more sensitive than conventional neuropsychological paper-pencil tests. It can be performed in short time and has the potential to be used as a fast and accurate screening tool that allows the initiation of comprehensive neuropsychological diagnostics and therapy from early on.

Theta burst stimulation in neglect after stroke: functional outcome and response variability origins.

Spatial neglect is a strong and negative predictor of general functional outcome after stroke, and its therapy remains a challenge. Whereas inhibitory non-invasive brain stimulation over the contralesional, intact hemisphere has generally been shown to ameliorate neglect on a group level, a conspicuous variability of the effects at the individual level is typically observed. We aimed to assess the characteristics and determinants of the effects of inhibitory non-invasive brain stimulation in neglect, identifying which patients would respond to this therapeutic approach and which not. To this end, we prospectively included 60 patients with a subacute right-hemispheric stroke. In 30 patients with spatial neglect, continuous theta burst stimulation (cTBS) was applied over the left posterior parietal cortex in a randomized clinical trial, either in eight or 16 trains, or as sham stimulation. Thirty patients without neglect served as a control group. Neglect severity was measured with a neuropsychological test battery and the Catherine Bergego Scale, at admission to and at discharge from inpatient neurorehabilitation, as well as at 3 months follow-up. General functional outcome was assessed by means of the Functional Independence Measure and the Lucerne ICF-based Multidisciplinary Observation Scale. The impact of clinical and demographic factors was evaluated, and the influence of lesion location and extension was assessed by means of voxel-based lesion-symptom mapping. On a group level, both cTBS protocols (i.e. eight and 16 trains) significantly reduced neglect severity in both the Catherine Bergego Scale and the neuropsychological tests, at discharge and 3 months later. Furthermore, cTBS significantly improved general functional outcome. On an individual level, hierarchical cluster and voxel-based lesion-symptom mapping analyses revealed that the variability in the responses to cTBS is determined by the integrity of interhemispheric connections within the corpus callosum, in particular parieto-parietal connections. In cTBS responders, in whom neglect and general functional outcome were significantly improved, the corpus callosum was intact, whereas this was not the case in cTBS non-responders. Moreover, analyses based on the proportional recovery rule and the Maugeri predictive stroke recovery model showed that the recovery of neglect and of the activities of daily living was accelerated only in cTBS responders. Furthermore, the level of activities of daily living recovery of these neglect patients was brought close to the one of right-hemispheric control patients without neglect. Hence, in neglect patients with intact interhemispheric connectivity, cTBS over the contralesional posterior parietal cortex significantly improves and accelerates neglect recovery and, associated with it, general functional outcome.

Pure optic ataxia and visual hemiagnosia - extending the dual visual hypothesis.

Goodale and Milner's two visual system hypothesis is an influential model for the understanding of the primate visual system. Lesions of either the ventral (occipito-temporal) or the dorsal (occipito-parietal) stream produce distinct and dissociated syndromes in humans: visual agnosia is typical for ventral damage, whereas optic ataxia (OA) for dorsal damage. We studied the case of a 59-year-old left-handed woman with a circumscribed lesion around the left posterior occipital sulcus, extending to the underlying white matter. Initially, she presented with a central visual field OA, which regressed to an OA to the right visual hemifield during the 3 months observation period. In addition, tachistoscopic experiments showed visual hemiagnosia to the right visual hemifield. In line with the findings of the neuropsychological experiments, the analysis of the structural MR data by means of a trackwise hodologic probabilistic approach revealed damage to the left superior longitudinal fasciculus and to the left inferior longitudinal fasciculus, indicating an impairment of both the dorsal and the ventral stream. The combination of OA and visual hemiagnosia in the same patient has never been previously described. The present case study thus provides further insights for the understanding of visual processing.

Contralesional Trunk Rotation Dissociates Real vs. Pseudo-Visual Field Defects due to Visual Neglect in Stroke Patients.

In stroke patients, the clinical presentation of visual field defects (VFDs) is frequently accompanied by visual neglect, i.e., the inability to attend and respond to the contralesional space. However, the diagnostic discrimination between the lack of reactions to contralesional stimuli due to VFDs or visual neglect is challenging during clinical examination. This discrimination is particularly relevant, since both clinical pictures are associated with different therapeutic approaches and outcomes. The aim of this study was to systematically investigate the effectiveness of trunk rotation toward the contralesional side-a manipulation dissociating the coordinate system of the trunk from that of the head and eyes-in disentangling real VFDs from "pseudo-VFDs" that occur due to visual neglect. Twenty patients with a left-sided VFD after a right-hemispheric stroke (10 additionally showing visual neglect in neuropsychological testing, VFD + neglect; 10 without neglect, VFD) were tested with Goldmann perimetry in both standard and trunk rotation conditions. In the standard condition, both VFD and VFD + neglect patients showed a conspicuous narrowing of the left visual field. However, trunk rotation triggered strikingly different patterns of change in the two groups: it elicited a significant increase in visual field extension in the VFD + neglect group, but left visual field extension virtually unchanged in the VFD group. Our results highlight contralesional trunk rotation as a simple, viable manipulation to effectively and rapidly disentangle real VFDs from "pseudo-VFDs" (i.e., due to visual neglect) during clinical examination.

Spatial Neglect Predicts Upper Limb Use in the Activities of Daily Living.

BACKGROUND AND PURPOSE: Motor tests performed at stroke onset have been shown to predict the recovery of upper limb motor impairment. Less is known about upper limb recovery at the level of functional activity or of participation and how spatial neglect may influence the integration of the upper limb in the activities of daily living (ADL). Our objective was to investigate whether the initial severity of spatial neglect may predict upper limb use in ADL. METHODS: Eighty-two patients with a right-hemispheric stroke (RHS) were prospectively included in the study. They were assessed twice in the acute/subacute and in the subacute/chronic phases (mean time interval of 45 days) after stroke. The Catherine Bergego Scale (CBS) was used to quantify the influence of spatial neglect on the ADL. Contralesional upper limb use in the ADL was evaluated with the Lucerne international classification of function, disability and health-based Multidisciplinary Observation Scale. Hand strength was measured using the Jamar, dexterity with the Nine Hole Peg test, and tactile perception using the stereognosis subtest of the Nottingham Sensory Assessment. Cognitive functions were assessed with the Montreal Cognitive Assessment. RESULTS: Regression analyses revealed that spatial neglect is an independent and a significant predictor of upper limb outcome. A CBS score of ≤5 at the time of admission to neurorehabilitation care was highly predictive for good upper limb use in the ADL 45 days later. CONCLUSIONS: This study demonstrates that spatial neglect severity, as observed in the ADL, is a significant and an independent predictor of upper limb outcome. Neglect therapy is thus needed to further improve contralesional upper limb use in the ADL in RHS patients.

The Responsiveness of the Lucerne ICF-Based Multidisciplinary Observation Scale: A Comparison with the Functional Independence Measure and the Barthel Index.

BACKGROUND: Good responsive functional outcome measures are important to measure change in stroke patients. The aim of study was to compare the internal and external responsiveness, floor and ceiling effects of the motor, cognition, and communication subscales of the Lucerne ICF-based Multidisciplinary Observation Scale (LIMOS) with the motor and cognition subscales of the Functional Independence Measure (FIM), and the Barthel Index (BI), in a large cohort of stroke patients. METHODS: One hundred eighteen stroke patients participated in this study. Admission and discharge score distributions of the LIMOS motor, LIMOS cognition and communication, FIM motor and FIM cognition, and BI were analyzed based on skewness and kurtosis. Floor and ceiling effects of the scales were determined. Internal responsiveness was assessed with t-tests, effect sizes (ESs), and standardized response means (SRMs). External responsiveness was investigated with linear regression analyses. RESULTS: The LIMOS motor and LIMOS cognition and communication subscales were more responsive, expressed by higher ESs (ES = 0.65, SRM = 1.17 and ES = 0.52, SRM = 1.17, respectively) as compared with FIM motor (ES = 0.54, SRM = 0.96) and FIM cognition (ES = 0.41, SRM = 0.88) and the BI (ES = 0.41, SRM = 0.65). The LIMOS subscales showed neither floor nor ceiling effects at admission and discharge (all <15%). In contrast, ceiling effects were found for the FIM motor (16%), FIM cognition (15%) at discharge and the BI at admission (22%) and discharge (43%). LIMOS motor and LIMOS cognition and communication subscales significantly correlated (p < 0.0001) with a change in the FIM motor and FIM cognition subscales, suggesting good external responsiveness. CONCLUSION: We found that the LIMOS motor and LIMOS cognition and communication, which are ICF-based multidisciplinary standardized observation scales, might have the potential to better detect changes in functional outcome of stroke patients, compared with the FIM motor and FIM cognition and the BI.

The relevance of cortical lesions in patients with multiple sclerosis.

BACKGROUND: Recent studies suggest that cortical lesions in multiple sclerosis (MS) substantially contribute to clinical disease severity. The present study aimed at investigating clinical, neuroanatomical, and cognitive correlates of these cortical lesions with a novel approach, i.e. by comparing two samples of relapsing-remitting multiple sclerosis (RRMS) patients, one group with and the other without cortical lesions. METHODS: High-resolution structural MRI was acquired from 42 RRMS patients and 43 controls (HC). The patient group was dichotomized based on the presence versus absence of DIR-hyperintense cortex-involving lesions, resulting in a cortical lesion group (CL, n = 32) and a non-cortical lesion group (nCL, n =10). Cognitive functioning was assessed in all participants with a comprehensive neuropsychological battery, covering mnestic, executive, and attentional functions. RESULTS: Highest densities of cortical lesions in the CL group were observed in the bilateral parahippocampal gyrus. Relative to HC, patients with cortical lesions - but not those without - showed significant global cortical thinning and mnestic deficits. The two patient groups did not differ from each other regarding demographic and basic disease characteristics such as EDSS scores. CONCLUSION: The appearance of cortical lesions in MS patients is associated with cortical thinning as well as mnestic deficits, which might be key characteristics of a 'cortically dominant' MS subtype.

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

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

Cognitive Impairment in Multiple Sclerosis: Clinical Manifestation, Neuroimaging Correlates, and Treatment.

Cognitive impairment is found in up to 70% of patients with multiple sclerosis (MS). Once thought of as a variant of subcortical dementia with a characteristic set of deficits, we now know that MS-related cognitive impairment can have many faces. This conceptual change in neuropsychology is embedded in a paradigm shift in the neuroscientific understanding of MS over the past 25 years: Partly based on modern neuroimaging techniques, the classical view of MS as an inflammatory demyelinating disease affecting the white matter of the central nervous system has been extended. In particular, many studies have shown that the MS pathology also includes neurodegeneration, and that gray matter structures such as the cerebral cortex can also show focal lesions, atrophy, or both. The authors present an updated summary of the clinical manifestation and neuroimaging correlates of cognitive impairment in MS, and discuss the relatively few treatment options available to date.

Cortical thinning in the anterior cingulate cortex predicts multiple sclerosis patients' fluency performance in a lateralised manner.

Cognitive impairment is as an important feature of Multiple Sclerosis (MS), and might be even more relevant to patients than mobility restrictions. Compared to the multitude of studies investigating memory deficits or basic cognitive slowing, executive dysfunction is a rarely studied cognitive domain in MS, and its neural correlates remain largely unexplored. Even rarer are topological studies on specific cognitive functions in MS. Here we used several structural MRI parameters - including cortical thinning and T2 lesion load - to investigate neural correlates of executive dysfunction, both on a global and a regional level by means of voxel- and vertex-wise analyses. Forty-eight patients with relapsing-remitting MS and 48 healthy controls participated in the study. Five executive functions were assessed, i.e. verbal and figural fluency, working memory, interference control and set shifting. Patients scored lower than controls in verbal and figural fluency only, and displayed widespread cortical thinning. On a global level, cortical thickness independently predicted verbal fluency performance, when controlling for lesion volume and central brain atrophy estimates. On a regional level, cortical thinning in the anterior cingulate region correlated with deficits in verbal and figural fluency and did so in a lateralised manner: Left-sided thinning was related to reduced verbal - but not figural - fluency, whereas the opposite pattern was observed for right-sided thinning. We conclude that executive dysfunction in MS patients can specifically affect verbal and figural fluency. The observed lateralised clinico-anatomical correlation has previously been described in brain-damaged patients with large focal lesions only, for example after stroke. Based on focal grey matter atrophy, we here show for the first time comparable lateralised findings in a white matter disease with widespread pathology.

Bottom-up Visual Integration in the Medial Parietal Lobe.

Largely based on findings from functional neuroimaging studies, the medial parietal lobe is known to contribute to internally directed cognitive processes such as visual imagery or episodic memory. Here, we present 2 patients with behavioral impairments that extend this view. Both had chronic unilateral lesions of nearly the entire medial parietal lobe, but in opposite hemispheres. Routine neuropsychological examination conducted >4 years after the onset of brain damage showed little deficits of minor severity. In contrast, both patients reported persistent unusual visual impairment. A comprehensive series of tachistoscopic experiments with lateralized stimulus presentation and comparison with healthy participants revealed partial visual hemiagnosia for stimuli presented to their contralesional hemifield, applying inferential single-case statistics to evaluate deficits and dissociations. Double dissociations were found in 4 experiments during which participants had to integrate more than one visual element, either through comparison or formation of a global gestalt. Against the background of recent neuroimaging findings, we conclude that of all medial parietal structures, the precuneus is the most likely candidate for a crucial involvement in such bottom-up visual integration.

Validation of the new Lucerne ICF based Multidisciplinary Observation Scale (LIMOS) for stroke patients.

BACKGROUND: Valid and multidisciplinary assessment of a stroke patient's ability to perform activities of daily living is very important to define individual goals and to plan targeted rehabilitation. Until today, there is no observation scale that relies on International Classification of Functioning, Disability and Health (ICF). The aim of the present study was to develop and evaluate the reliability and validity of a new multidisciplinary observation scale for stroke patients, shortly called LIMOS, which is based on ICF. METHODS: In a first phase, LIMOS was defined, using a Delphi approach, by an expert panel and a pilot testing was conducted in a small group of stroke patients (n =10) to investigate feasibility and practicability. In a second phase, LIMOS was assessed for its reliability (internal consistency and test-retest reliability) and validity in a large cohort of stroke patients (n = 102). For convergent validity, the correlation between total scores of the LIMOS and the Functional Independence Measure (FIM) was assessed. RESULTS: LIMOS consisted of seven ICF chapters incorporating 45 domains. A high internal consistency (=0.98) of LIMOS was found. Furthermore, good test-retest reliability at item and subscale level was found. Principal component analysis revealed that among the seven ICF chapters, four components could be found: (1) interpersonal activities, mobility and self-care, (2) communication, (3) knowledge and general tasks, and (4) domestic life. Significant associations were found between LIMOS and the FIM indicating good convergent validity. CONCLUSIONS: The new LIMOS is a reliable and valid observation scale for stroke patients based on ICF, which can be used by a multidisciplinary team working in a neurorehabilitation setting.

Do patients with pure alexia suffer from a specific word form processing deficit? Evidence from 'wrods with trasnpsoed letetrs'.

It is widely accepted that letter-by-letter reading and a pronounced increase in reading time as a function of word length are the hallmark features of pure alexia. Why patients show these two phenomena with respect to underlying cognitive mechanisms is, however, much less clear. Two main hypotheses have been proposed, i.e. impaired discrimination of letters and deficient processing of word forms. While the former deficit can easily be investigated in isolation, previous findings favouring the latter seem confounded. Applying a word reading paradigm with systematically manipulated letter orders in two patients with pure alexia, we demonstrate a word form processing deficit that is not attributable to sublexical letter discrimination difficulties. Moreover, pure alexia-like fixation patterns could be induced in healthy adults by having them read sentences including words with transposed letters, so-called 'jumbled words'. This further corroborates a key role of deficient word form processing in pure alexia. With regard to basic reading research, the present study extends recent evidence for relative, rather than precise, encoding of letter position in the brain.

About the role of visual field defects in pure alexia.

Pure alexia is an acquired reading disorder characterized by a disproportionate prolongation of reading time as a function of word length. Although the vast majority of cases reported in the literature show a right-sided visual defect, little is known about the contribution of this low-level visual impairment to their reading difficulties. The present study was aimed at investigating this issue by comparing eye movement patterns during text reading in six patients with pure alexia with those of six patients with hemianopic dyslexia showing similar right-sided visual field defects. We found that the role of the field defect in the reading difficulties of pure alexics was highly deficit-specific. While the amplitude of rightward saccades during text reading seems largely determined by the restricted visual field, other visuo-motor impairments-particularly the pronounced increases in fixation frequency and viewing time as a function of word length-may have little to do with their visual field defect. In addition, subtracting the lesions of the hemianopic dyslexics from those found in pure alexics revealed the largest group differences in posterior parts of the left fusiform gyrus, occipito-temporal sulcus and inferior temporal gyrus. These regions included the coordinate assigned to the centre of the visual word form area in healthy adults, which provides further evidence for a relation between pure alexia and a damaged visual word form area. Finally, we propose a list of three criteria that may improve the differential diagnosis of pure alexia and allow appropriate therapy recommendations.