The role of nonverbal communication in patients with post-stroke language impairment (aphasia) is... more The role of nonverbal communication in patients with post-stroke language impairment (aphasia) is not yet fully understood. This study investigated how aphasic patients perceive and produce co-speech gestures during face-to-face interaction, and whether distinct brain lesions would predict the frequency of spontaneous co-speech gesturing. For this purpose, we recorded samples of conversations in patients with aphasia and healthy participants. Gesture perception was assessed by means of a head-mounted eye-tracking system, and the produced co-speech gestures were coded according to a linguistic classification system. The main results are that meaning-laden gestures (e.g., iconic gestures representing object shapes) are more likely to attract visual attention than meaningless hand movements, and that patients with aphasia are more likely to fixate co-speech gestures overall than healthy participants. This implies that patients with aphasia may benefit from the multimodal information provided by co-speech gestures. On the level of co-speech gesture production, we found that patients with damage to the anterior part of the arcuate fasciculus showed a higher frequency of meaning-laden gestures. This area lies in close vicinity to the premotor cortex and is considered to be important for speech production. This may suggest that the use of meaning-laden gestures depends on the integrity of patients' speech production abilities.
When healthy observers make a saccade that is erroneously directed toward a distracter stimulus, ... more When healthy observers make a saccade that is erroneously directed toward a distracter stimulus, they often produce a corrective saccade within 100ms after the end of the primary saccade. Such short inter-saccadic intervals indicate that programming of the secondary saccade has been initiated prior to the execution of the primary saccade and hence that the two saccades have been programmed concurrently. Here we show that concurrent saccade programming is bilaterally impaired in left spatial neglect, a strongly lateralized disorder of visual attention resulting from extensive right cerebral damage. Neglect patients were asked to make saccades to targets presented left or right of fixation while disregarding a distracter presented in the opposite hemifield. We examined those experimental trials on which participants first made a saccade to the distracter, followed by a secondary (corrective) saccade to the target. Compared to healthy and right-hemisphere damaged control participants the proportion of secondary saccades directing gaze to the target instead of bringing it even closer to the distracter was bilaterally reduced in neglect patients. In addition, the characteristic reduction of secondary saccade latency observed in both control groups was absent in neglect patients, whether the secondary saccade was directed to the left or right hemifield. This pattern is consistent with a severe, bilateral impairment of concurrent saccade programming in left spatial neglect.
Nonverbal communication Structural connectivity local efficiency of the praxis network. Furthermo... more Nonverbal communication Structural connectivity local efficiency of the praxis network. Furthermore, reduced tract integrity, for example in the superior longitudinal fascicle, arcuate fascicle or corpus callosum were related to gesture deficits. Our findings contribute to the understanding of structural correlates of gesture production as they first present diffusion tensor imaging data in a combined sample of healthy subjects and a patient cohort with gestural deficits.
The representation and processing of numerosity is a crucial cognitive capacity. Converging evide... more The representation and processing of numerosity is a crucial cognitive capacity. Converging evidence points to the posterior parietal cortex (PPC) as primary “number” region. However, the exact role of the left and right PPC for different types of numerical and arithmetic tasks remains controversial. In this study, we used high-definition transcranial direct current stimulation (HD-tDCS) to further investigate the causal involvement of the PPC during approximative, nonsymbolic mental arithmetic. Eighteen healthy participants received three sessions of anodal HD-tDCS at 1-week intervals in counterbalanced order: left PPC, right PPC, and sham stimulation. Results showed an improved performance during online parietal HD-tDCS (vs. sham) for subtraction problems. Specifically, the general tendency to underestimate the results of subtraction problems (i.e., the “operational momentum effect”) was reduced during online parietal HD-tDCS. There was no difference between left and right stimula...
Background: Visual search declines with aging, dementia, and brain injury and is linked to limita... more Background: Visual search declines with aging, dementia, and brain injury and is linked to limitations in everyday activities. Recent studies suggest that visual search can be improved with practice using computerized visual search tasks and puzzle video games. For practical use, it is important that visual search ability can be assessed and practiced in a controlled and adaptive way. However, commercial puzzle video games make it hard to control task difficulty, and there are little means to collect performance data. Objective: The aim of this study was to develop and initially validate the search and match task (SMT) that combines an enjoyable tile-matching match-3 puzzle video game with features of the visual search paradigm (taskified game). The SMT was designed as a single-target visual search task that allows control over task difficulty variables and collection of performance data. Methods: The SMT is played on a grid-based (width × height) puzzle board, filled with different types of colored polygons. A wide range of difficulty levels was generated by combinations of 3 task variables over a range from 4 to 8 including height and width of the puzzle board (set size) and the numbers of tile types (distractor heterogeneity). For each difficulty level, large numbers of playable trials were pregenerated using Python. Each trial consists of 4 consecutive puzzle boards, where the goal of the task is to find a target tile configuration (search) on the puzzle board and swap 2 adjacent tiles to create a line of 3 identical tiles (match). For each puzzle board, there is exactly 1 possible match (single target search). In a user study with 28 young adults (aged 18 to 31 years), 13 older (aged 64 to 79 years) and 11 oldest (aged 86 to 98 years) adults played the long (young and older adults) or short version (oldest adults) of the difficulty levels of the SMT. Participants rated their perception and the usability of the task and completed neuropsychological tests that measure cognitive domains engaged by the puzzle game. Results: Results from the user study indicate that the target search time is associated with set size, distractor heterogeneity, and age. Results further indicate that search performance is associated with general cognitive ability, selective and divided attention, visual search, and visuospatial and pattern recognition ability. Conclusions: Overall, this study shows that an everyday puzzle game-based task can be experimentally controlled, is enjoyable and user-friendly, and permits data collection to assess visual search and cognitive abilities. Further research is needed to evaluate the potential of the SMT game to assess and practice visual search ability in an enjoyable and adaptive way. A PsychoPy version of the SMT is freely available for researchers.
Background: Crossing a street can be a very difficult task for older pedestrians. With increased ... more Background: Crossing a street can be a very difficult task for older pedestrians. With increased age and potential cognitive decline, older people take the decision to cross a street primarily based on vehicles' distance, and not on their speed. Furthermore, older pedestrians tend to overestimate their own walking speed, and could not adapt it according to the traffic conditions. Pedestrians' behavior is often tested using virtual reality. Virtual reality presents the advantage of being safe, cost-effective, and allows using standardized test conditions. Methods: This paper describes an observational study with older and younger adults. Street crossing behavior was investigated in 18 healthy, younger and 18 older subjects by using a virtual reality setting. The aim of the study was to measure behavioral data (such as eye and head movements) and to assess how the two age groups differ in terms of number of safe street crossings, virtual crashes, and missed street crossing opportunities. Street crossing behavior, eye and head movements, in older and younger subjects, were compared with non-parametric tests. Results: The results showed that younger pedestrians behaved in a more secure manner while crossing a street, as compared to older people. The eye and head movements analysis revealed that older people looked more at the ground and less at the other side of the street to cross. Conclusions: The less secure behavior in street crossing found in older pedestrians could be explained by their reduced cognitive and visual abilities, which, in turn, resulted in difficulties in the decision-making process, especially under time pressure. Decisions to cross a street are based on the distance of the oncoming cars, rather than their speed, for both groups. Older pedestrians look more at their feet, probably because of their need of more time to plan precise stepping movement and, in turn, pay less attention to the traffic. This might help to set up guidelines for improving senior pedestrians' safety, in terms of speed limits, road design, and mixed physical-cognitive trainings.
Background: Behavioral changes are common in patients with multiple sclerosis (MS), however not a... more Background: Behavioral changes are common in patients with multiple sclerosis (MS), however not as readily recognized as cognitive impairments. Objective: The aim of this study was to analyze behavioral changes and its relation to disease characteristics, disability, and cognitive impairments in patients with MS. Method: This is a single-center cross-sectional study. A detailed neuropsychological examination, including the Frontal Systems Behavior Scale (FrSBe), the Beck depression inventory (BDI), and the Wuerzburg Fatigue Inventory for Multiple Sclerosis (WEIMuS) test, was performed. FrSBe results were correlated with disease characteristics, disability, and cognitive assessments. results: 66 patients were enrolled (mean age: 43.4 years; disease duration: 9.3 years; Expanded Disability Status Scale: 3.0). Up to one third of patients showed behavioral changes in at least one domain or the total score of the FrSBe. Patients were mildly affected with regard to cognitive functioning. Consistent correlation was found between behavioral changes and fatigue (WEIMuS) and depressive symptoms (BDI), but not with disease characteristics, disability, or cognitive functions. There was an increase of behavioral changes on all FrSBe scales in the current status compared to the retrospectively rated status before disease onset. Self-and family ratings with regard to current behavioral changes were similar. conclusion: Behavioral changes are common in otherwise mildly affected MS patients with up to one third being affected. In this patient cohort, behavioral changes occur largely independent of disease characteristics, physical disability, and cognitive functioning but correlate with both fatigue and depressive symptoms. Therefore, they should be tested specifically.
Schizophrenia is characterized by social interaction deficits contributing to poor functional out... more Schizophrenia is characterized by social interaction deficits contributing to poor functional outcome. Hand gesture use is particularly impaired, linked to frontal lobe dysfunction and frontal grey matter deficits. The functional neural correlates of impaired gesturing are currently unclear. We therefore investigated aberrant brain activity during impaired gesturing in schizophrenia. We included 22 patients with schizophrenia and 25 healthy control participants matched for age, gender, and education level. We obtained functional magnetic resonance imaging data using an event-related paradigm to assess brain activation during gesture planning and execution. Group differences in whole brain effects were calculated using factorial designs. Gesture ratings were performed by a single rater, blind to diagnoses and clinical presentation. During gesture planning and execution both groups activated brain areas of the praxis network. However, patients had reduced dorsolateral prefrontal corte...
Recent research provides evidence that galvanic vestibular stimulation (GVS) has a modulating eff... more Recent research provides evidence that galvanic vestibular stimulation (GVS) has a modulating effect on somatosensory perception and spatial cognition. However, other vestibular stimulation techniques have induced changes in affective control and decision making. The aim of this study was to investigate the effect of GVS on framing susceptibility in a risky-choice game. The participants were to decide between a safe and a risky option. The safe option was framed either positively or negatively. During the task, the participants were exposed to either left anodal/right cathodal GVS, right anodal/left cathodal GVS, or sham stimulation (control condition). While left anodal/right cathodal GVS activated more right-hemispheric vestibular brain areas, right anodal/left cathodal GVS resulted in more bilateral activation. We observed increased framing susceptibility during left anodal/right cathodal GVS, but no change in framing susceptibility during right anodal/left cathodal GVS. We propo...
Cerebral cortex (New York, N.Y. : 1991), Jan 23, 2016
With a reduced level of alertness, healthy individuals typically show a rightward shift when depl... more With a reduced level of alertness, healthy individuals typically show a rightward shift when deploying visual attention in space. The impact of alertness on the neural networks governing visuospatial attention is, however, poorly understood. By using a transcranial magnetic stimulation twin-coil approach, the present study aimed at investigating the effects of an alertness manipulation on the excitability of the left and the right posterior parietal cortices (PPCs), crucial nodes of the visuospatial attentional network. Participants' visuospatial attentional deployment was assessed with a free visual exploration task and concurrent eye tracking. Their alertness level was manipulated through the time of the day, that is, by testing chronotypically defined evening types both during their circadian on- and off-peak times. The results revealed an increased excitability of the left compared with the right PPC during low alertness. On the horizontal dimension, these results were accom...
Background/Aim: Gesturing plays an important role in social behavior and social learning. Deficit... more Background/Aim: Gesturing plays an important role in social behavior and social learning. Deficits are frequent in schizophrenia and may contribute to impaired social functioning. Information about deficits during the course of the disease and presence of severity and patterns of impairment in first-episode patients is missing. Hence, we aimed to investigate gesturing in first- compared to multiple-episode schizophrenia patients and healthy controls. Methods: In 14 first-episode patients, 14 multiple-episode patients and 16 healthy controls matched for age, gender and education, gesturing was assessed by the comprehensive Test of Upper Limb Apraxia. Performance in two domains of gesturing - imitation and pantomime - was recorded on video. Raters of gesture performance were blinded. Results: Patients with multiple episodes had severe gestural deficits. For almost all gesture categories, performance was worse in multiple- than in first-episode patients. First-episode patients demonstr...
Introduction: The neural correlates of impaired performance of gestures are currently unclear. Le... more Introduction: The neural correlates of impaired performance of gestures are currently unclear. Lesion studies showed variable involvement of the ventro-dorsal stream particularly left inferior frontal gyrus (IFG) in gesture performance on command. However, findings cannot be easily generalized as lesions may be biased by the architecture of vascular supply and involve brain areas beyond the critical region. The neuropsychiatric syndrome of schizophrenia shares apraxic-like errors and altered brain structure without macroanatomic lesions. Schizophrenia may therefore qualify as a model disorder to test neural correlates of gesture impairments. Methods: We included 45 schizophrenia patients and 44 healthy controls in the study to investigate the structural brain correlates of defective gesturing in schizophrenia using voxel based morphometry. Gestures were tested in two domains: meaningful gestures (transitive and intransitive) on verbal command and imitation of meaningless gestures. Cutoff scores were used to separate patients with deficits, patients without deficits and controls. Group differences in GM volume were explored in an ANCOVA. Results: Patients performed poorer than controls in each gesture category (p < 0.001). Patients with deficits in producing meaningful gestures on command had reduced gray matter (GM) predominantly in left IFG, with additional involvement of right insula and anterior cingulate cortex. Patients with deficits differed from patients without deficits in right insula, inferior parietal lobe and superior temporal gyrus. Conclusions: Impaired performance of meaningful gestures on command was linked to volume loss predominantly in the praxis network in schizophrenia. Thus, the behavioral similarities between apraxia and schizophrenia are paralleled by structural alterations.
We aimed at further elucidating whether aphasic patients' difficulties in understanding non-c... more We aimed at further elucidating whether aphasic patients' difficulties in understanding non-canonical sentence structures, such as Passive or Object-Verb-Subject sentences, can be attributed to impaired morphosyntactic cue recognition, and to problems in integrating competing interpretations. A sentence-picture matching task with canonical and non-canonical spoken sentences was performed using concurrent eye tracking. Accuracy, reaction time, and eye tracking data (fixations) of 50 healthy subjects and 12 aphasic patients were analysed. Patients showed increased error rates and reaction times, as well as delayed fixation preferences for target pictures in non-canonical sentences. Patients' fixation patterns differed from healthy controls and revealed deficits in recognizing and immediately integrating morphosyntactic cues. Our study corroborates the notion that difficulties in understanding syntactically complex sentences are attributable to a processing deficit encompassing...
BACKGROUND In a high proportion of patients with favorable outcome after aneurysmal subarachnoid ... more BACKGROUND In a high proportion of patients with favorable outcome after aneurysmal subarachnoid hemorrhage (aSAH), neuropsychological deficits, depression, anxiety, and fatigue are responsible for the inability to return to their regular premorbid life and pursue their professional careers. These problems often remain unrecognized, as no recommendations concerning a standardized comprehensive assessment have yet found entry into clinical routines. METHODS To establish a nationwide standard concerning a comprehensive assessment after aSAH, representatives of all neuropsychological and neurosurgical departments of those eight Swiss centers treating acute aSAH have agreed on a common protocol. In addition, a battery of questionnaires and neuropsychological tests was selected, optimally suited to the deficits found most prevalent in aSAH patients that was available in different languages and standardized. RESULTS We propose a baseline inpatient neuropsychological screening using the Montreal Cognitive Assessment (MoCA) between days 14 and 28 after aSAH. In an outpatient setting at 3 and 12 months after bleeding, we recommend a neuropsychological examination, testing all relevant domains including attention, speed of information processing, executive functions, verbal and visual learning/memory, language, visuo-perceptual abilities, and premorbid intelligence. In addition, a detailed assessment capturing anxiety, depression, fatigue, symptoms of frontal lobe affection, and quality of life should be performed. CONCLUSIONS This standardized neuropsychological assessment will lead to a more comprehensive assessment of the patient, facilitate the detection and subsequent treatment of previously unrecognized but relevant impairments, and help to determine the incidence, characteristics, modifiable risk factors, and the clinical course of these impairments after aSAH.The need for clinically applicable skin substitutes continues to be a matter of fact. Hypothetically, a laboratory grown autologous skin analog with near normal architecture might be a suitable approach to yield both satisfactory functional and cosmetic long-term results. In this study, we explored the use of human endothelial cells derived from freshly isolated adipose stromal vascular fraction (SVF) in a three-dimensional (3D) coculture model of vascularized bio-engineered skin substitute. METHODS The SVF was isolated from human white adipose tissue samples and keratinocytes from human skin biopsies. The SVF, in particular endothelial cells, were characterized using flow cytometry and immuofluorescence analysis. Endothelial and mesenchymal progenitors from the SVF formed blood capillaries after seeding into a 3D collagen type I hydrogel in vitro. Subsequently, human keratinocytes were seeded on the top of those hydrogels to develop a vascularized dermo-epidermal skin substitute. RESULTS Flow cytometric analysis of surface markers of the freshly isolated SVF showed the expression of endothelial markers (CD31, CD34, CD146), mesenchymal/stromal cell-associated markers (CD44, CD73, CD90, CD105), stem cell markers (CD49f, CD117, CD133), and additionally hematopoietic markers (CD14, CD15, CD45). Further analysis of white adipose-derived endothelial cells (watECs) revealed the co-expression of CD31, CD34, CD90, CD105, and partially CD146 on these cells. WatECs were separated from adipose-stromal cells (watASCs) using FACS sorting. WatASCs and watECs cultured separately in a 3D hydrogel for 3 weeks did not form any vascular structures. Only if co-cultured, both cell types aligned to develop a ramified vascular network in vitro with continuous endothelial lumen formation. Transplantation of those 3D-hydrogels onto immuno-incompetent rats resulted in a rapid connection of human capillaries with the host vessels and formation of functional, blood-perfused mosaic human-rat vessels within only 3-4 days. CONCLUSIONS Adipose tissue represents an attractive cell source due to the ease of isolation and abundance of endothelial as well as mesenchymal cell lineages. Adipose-derived SVF cells exhibit the ability to form microvascular structures in vitro and support the accelerated blood perfusion in skin substitutes in vivo when transplanted.
Converging evidences from eye movement experiments indicate that linguistic contexts influence re... more Converging evidences from eye movement experiments indicate that linguistic contexts influence reading strategies. However, the question of whether different linguistic contexts modulate eye movements during reading in the same bilingual individuals remains unresolved. We examined reading strategies in a transparent (German) and an opaque (French) language of early, highly proficient French–German bilinguals: participants read aloud isolated French and German words and pseudo-words while the First Fixation Location (FFL), its duration and latency were measured. Since transparent linguistic contexts and pseudo-words would favour a direct grapheme/phoneme conversion, the reading strategy should be more local for German than for French words (FFL closer to the beginning) and no difference is expected in pseudo-words’ FFL between contexts. Our results confirm these hypotheses, providing the first evidence that the same individuals engage different reading strategy depending on language ...
Aphasia is a common syndrome after left-lateralized stroke and is characterized by partial or tot... more Aphasia is a common syndrome after left-lateralized stroke and is characterized by partial or total loss of language functions. Functional imaging studies examining language recovery after stroke often find an overactivation of the non-damaged right hemisphere. One hypothesis is that the overactivation is dysfunctional which is explained within the framework of interhemispheric inhibition. Non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) allow modulating cortical activity and may thereby offer novel therapeutic opportunities. A repetitive TMS protocol named theta burst stimulation (TBS) is increasingly used in clinical research. It has the advantage of a short application time combined with prolonged aftereffects. In a previous study we found better naming performance in aphasic patients after the application of one train of TBS over the right Broca's homologue. Applying TBS trains repeatedly can furthermore disproportionately prolong the effects, as was for example shown in neglect patients. Thus, repeated trains of TBS are applied in the present study in a randomized, sham controlled, cross-over design. After comprehensive baseline testing, eight TBS trains and eight sham stimulation trains are applied over the right Broca's homologue on two consecutive days separated by one week. On the second days of stimulation, several short language tests are administered. A follow-up with comprehensive language testing takes place one month after the stimulation. Preliminary results of this ongoing study will be presented. The aim of the study is to evaluate the effects of repeated TBS on several language tasks over a longer time span.
This study investigated the roles of the right and left dorsolateral prefrontal (rDLPFC, lDLPFC) ... more This study investigated the roles of the right and left dorsolateral prefrontal (rDLPFC, lDLPFC) and the medial frontal cortex (MFC) in executive functioning using a theta burst transcranial magnetic stimulation (TMS) approach. Healthy subjects solved two visual search tasks: a number search task with low cognitive demands, and a number and letter search task with high cognitive demands. To observe how subjects solved the tasks, we assessed their behavior with and without TMS using eye movements when subjects were confronted with specific executive demands. To observe executive functions, we were particularly interested in TMS-induced changes in visual exploration strategies found to be associated with good or bad performance in a control condition without TMS stimulation. TMS left processing time unchanged in both tasks. Inhibition of the rDLPFC resulted in a decrease in anticipatory fixations in the number search task, i.e., a decrease in a good strategy in this low demand task. This was paired with a decrease in stimulus fixations. Together, these results point to a role of the rDLPFC in planning and response selection. Inhibition of the lDLPFC and the MFC resulted in an increase in anticipatory fixations in the number and letter search task, i.e., an increase in the application of a good strategy in this task. We interpret these results as a compensatory strategy to account for TMS-induced deficits in attentional switching when faced with high switching demands. After inhibition of the lDLPFC, an increase in regressive fixations was found in the number and letter search task. In the context of high working memory demands, this strategy appears to support TMS-induced working memory deficits. Combining an experimental TMS approach with the recording of eye movements proved sensitive to discrete decrements of executive functions and allows pinpointing the functional organization of the frontal lobes.
Previous work has reported that in the Iowa gambling task (IGT) advantageous decisions may be tak... more Previous work has reported that in the Iowa gambling task (IGT) advantageous decisions may be taken before the advantageous strategy is known [Bechara, A., Damasio, H., Tranel, D., &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp; Damasio, A. R. (1997). Deciding advantageously before knowing the advantageous strategy. Science, 275, 1293-1295]. In order to test whether explicit memory is essential for the acquisition of a behavioural preference for advantageous choices, we measured behavioural performance and skin conductance responses (SCRs) in five patients with dense amnesia following damage to the basal forebrain and orbitofrontal cortex, six amnesic patients with damage to the medial temporal lobe or the diencephalon, and eight control subjects performing the IGT. Across 100 trials healthy participants acquired a preference for advantageous choices and generated large SCRs to high levels of punishment. In addition, their anticipatory SCRs to disadvantageous choices were larger than to advantageous choices. However, this dissociation occurred much later than the behavioural preference for advantageous alternatives. In contrast, though exhibiting discriminatory autonomic SCRs to different levels of punishment, 9 of 11 amnesic patients performed at chance and did not show differential anticipatory SCRs to advantageous and disadvantageous choices. Further, the magnitude of anticipatory SCRs did not correlate with behavioural performance. These results suggest that the acquisition of a behavioural preference--be it for advantageous or disadvantageous choices--depends on the memory of previous reinforcements encountered in the task, a capacity requiring intact explicit memory.
The role of nonverbal communication in patients with post-stroke language impairment (aphasia) is... more The role of nonverbal communication in patients with post-stroke language impairment (aphasia) is not yet fully understood. This study investigated how aphasic patients perceive and produce co-speech gestures during face-to-face interaction, and whether distinct brain lesions would predict the frequency of spontaneous co-speech gesturing. For this purpose, we recorded samples of conversations in patients with aphasia and healthy participants. Gesture perception was assessed by means of a head-mounted eye-tracking system, and the produced co-speech gestures were coded according to a linguistic classification system. The main results are that meaning-laden gestures (e.g., iconic gestures representing object shapes) are more likely to attract visual attention than meaningless hand movements, and that patients with aphasia are more likely to fixate co-speech gestures overall than healthy participants. This implies that patients with aphasia may benefit from the multimodal information provided by co-speech gestures. On the level of co-speech gesture production, we found that patients with damage to the anterior part of the arcuate fasciculus showed a higher frequency of meaning-laden gestures. This area lies in close vicinity to the premotor cortex and is considered to be important for speech production. This may suggest that the use of meaning-laden gestures depends on the integrity of patients' speech production abilities.
When healthy observers make a saccade that is erroneously directed toward a distracter stimulus, ... more When healthy observers make a saccade that is erroneously directed toward a distracter stimulus, they often produce a corrective saccade within 100ms after the end of the primary saccade. Such short inter-saccadic intervals indicate that programming of the secondary saccade has been initiated prior to the execution of the primary saccade and hence that the two saccades have been programmed concurrently. Here we show that concurrent saccade programming is bilaterally impaired in left spatial neglect, a strongly lateralized disorder of visual attention resulting from extensive right cerebral damage. Neglect patients were asked to make saccades to targets presented left or right of fixation while disregarding a distracter presented in the opposite hemifield. We examined those experimental trials on which participants first made a saccade to the distracter, followed by a secondary (corrective) saccade to the target. Compared to healthy and right-hemisphere damaged control participants the proportion of secondary saccades directing gaze to the target instead of bringing it even closer to the distracter was bilaterally reduced in neglect patients. In addition, the characteristic reduction of secondary saccade latency observed in both control groups was absent in neglect patients, whether the secondary saccade was directed to the left or right hemifield. This pattern is consistent with a severe, bilateral impairment of concurrent saccade programming in left spatial neglect.
Nonverbal communication Structural connectivity local efficiency of the praxis network. Furthermo... more Nonverbal communication Structural connectivity local efficiency of the praxis network. Furthermore, reduced tract integrity, for example in the superior longitudinal fascicle, arcuate fascicle or corpus callosum were related to gesture deficits. Our findings contribute to the understanding of structural correlates of gesture production as they first present diffusion tensor imaging data in a combined sample of healthy subjects and a patient cohort with gestural deficits.
The representation and processing of numerosity is a crucial cognitive capacity. Converging evide... more The representation and processing of numerosity is a crucial cognitive capacity. Converging evidence points to the posterior parietal cortex (PPC) as primary “number” region. However, the exact role of the left and right PPC for different types of numerical and arithmetic tasks remains controversial. In this study, we used high-definition transcranial direct current stimulation (HD-tDCS) to further investigate the causal involvement of the PPC during approximative, nonsymbolic mental arithmetic. Eighteen healthy participants received three sessions of anodal HD-tDCS at 1-week intervals in counterbalanced order: left PPC, right PPC, and sham stimulation. Results showed an improved performance during online parietal HD-tDCS (vs. sham) for subtraction problems. Specifically, the general tendency to underestimate the results of subtraction problems (i.e., the “operational momentum effect”) was reduced during online parietal HD-tDCS. There was no difference between left and right stimula...
Background: Visual search declines with aging, dementia, and brain injury and is linked to limita... more Background: Visual search declines with aging, dementia, and brain injury and is linked to limitations in everyday activities. Recent studies suggest that visual search can be improved with practice using computerized visual search tasks and puzzle video games. For practical use, it is important that visual search ability can be assessed and practiced in a controlled and adaptive way. However, commercial puzzle video games make it hard to control task difficulty, and there are little means to collect performance data. Objective: The aim of this study was to develop and initially validate the search and match task (SMT) that combines an enjoyable tile-matching match-3 puzzle video game with features of the visual search paradigm (taskified game). The SMT was designed as a single-target visual search task that allows control over task difficulty variables and collection of performance data. Methods: The SMT is played on a grid-based (width × height) puzzle board, filled with different types of colored polygons. A wide range of difficulty levels was generated by combinations of 3 task variables over a range from 4 to 8 including height and width of the puzzle board (set size) and the numbers of tile types (distractor heterogeneity). For each difficulty level, large numbers of playable trials were pregenerated using Python. Each trial consists of 4 consecutive puzzle boards, where the goal of the task is to find a target tile configuration (search) on the puzzle board and swap 2 adjacent tiles to create a line of 3 identical tiles (match). For each puzzle board, there is exactly 1 possible match (single target search). In a user study with 28 young adults (aged 18 to 31 years), 13 older (aged 64 to 79 years) and 11 oldest (aged 86 to 98 years) adults played the long (young and older adults) or short version (oldest adults) of the difficulty levels of the SMT. Participants rated their perception and the usability of the task and completed neuropsychological tests that measure cognitive domains engaged by the puzzle game. Results: Results from the user study indicate that the target search time is associated with set size, distractor heterogeneity, and age. Results further indicate that search performance is associated with general cognitive ability, selective and divided attention, visual search, and visuospatial and pattern recognition ability. Conclusions: Overall, this study shows that an everyday puzzle game-based task can be experimentally controlled, is enjoyable and user-friendly, and permits data collection to assess visual search and cognitive abilities. Further research is needed to evaluate the potential of the SMT game to assess and practice visual search ability in an enjoyable and adaptive way. A PsychoPy version of the SMT is freely available for researchers.
Background: Crossing a street can be a very difficult task for older pedestrians. With increased ... more Background: Crossing a street can be a very difficult task for older pedestrians. With increased age and potential cognitive decline, older people take the decision to cross a street primarily based on vehicles' distance, and not on their speed. Furthermore, older pedestrians tend to overestimate their own walking speed, and could not adapt it according to the traffic conditions. Pedestrians' behavior is often tested using virtual reality. Virtual reality presents the advantage of being safe, cost-effective, and allows using standardized test conditions. Methods: This paper describes an observational study with older and younger adults. Street crossing behavior was investigated in 18 healthy, younger and 18 older subjects by using a virtual reality setting. The aim of the study was to measure behavioral data (such as eye and head movements) and to assess how the two age groups differ in terms of number of safe street crossings, virtual crashes, and missed street crossing opportunities. Street crossing behavior, eye and head movements, in older and younger subjects, were compared with non-parametric tests. Results: The results showed that younger pedestrians behaved in a more secure manner while crossing a street, as compared to older people. The eye and head movements analysis revealed that older people looked more at the ground and less at the other side of the street to cross. Conclusions: The less secure behavior in street crossing found in older pedestrians could be explained by their reduced cognitive and visual abilities, which, in turn, resulted in difficulties in the decision-making process, especially under time pressure. Decisions to cross a street are based on the distance of the oncoming cars, rather than their speed, for both groups. Older pedestrians look more at their feet, probably because of their need of more time to plan precise stepping movement and, in turn, pay less attention to the traffic. This might help to set up guidelines for improving senior pedestrians' safety, in terms of speed limits, road design, and mixed physical-cognitive trainings.
Background: Behavioral changes are common in patients with multiple sclerosis (MS), however not a... more Background: Behavioral changes are common in patients with multiple sclerosis (MS), however not as readily recognized as cognitive impairments. Objective: The aim of this study was to analyze behavioral changes and its relation to disease characteristics, disability, and cognitive impairments in patients with MS. Method: This is a single-center cross-sectional study. A detailed neuropsychological examination, including the Frontal Systems Behavior Scale (FrSBe), the Beck depression inventory (BDI), and the Wuerzburg Fatigue Inventory for Multiple Sclerosis (WEIMuS) test, was performed. FrSBe results were correlated with disease characteristics, disability, and cognitive assessments. results: 66 patients were enrolled (mean age: 43.4 years; disease duration: 9.3 years; Expanded Disability Status Scale: 3.0). Up to one third of patients showed behavioral changes in at least one domain or the total score of the FrSBe. Patients were mildly affected with regard to cognitive functioning. Consistent correlation was found between behavioral changes and fatigue (WEIMuS) and depressive symptoms (BDI), but not with disease characteristics, disability, or cognitive functions. There was an increase of behavioral changes on all FrSBe scales in the current status compared to the retrospectively rated status before disease onset. Self-and family ratings with regard to current behavioral changes were similar. conclusion: Behavioral changes are common in otherwise mildly affected MS patients with up to one third being affected. In this patient cohort, behavioral changes occur largely independent of disease characteristics, physical disability, and cognitive functioning but correlate with both fatigue and depressive symptoms. Therefore, they should be tested specifically.
Schizophrenia is characterized by social interaction deficits contributing to poor functional out... more Schizophrenia is characterized by social interaction deficits contributing to poor functional outcome. Hand gesture use is particularly impaired, linked to frontal lobe dysfunction and frontal grey matter deficits. The functional neural correlates of impaired gesturing are currently unclear. We therefore investigated aberrant brain activity during impaired gesturing in schizophrenia. We included 22 patients with schizophrenia and 25 healthy control participants matched for age, gender, and education level. We obtained functional magnetic resonance imaging data using an event-related paradigm to assess brain activation during gesture planning and execution. Group differences in whole brain effects were calculated using factorial designs. Gesture ratings were performed by a single rater, blind to diagnoses and clinical presentation. During gesture planning and execution both groups activated brain areas of the praxis network. However, patients had reduced dorsolateral prefrontal corte...
Recent research provides evidence that galvanic vestibular stimulation (GVS) has a modulating eff... more Recent research provides evidence that galvanic vestibular stimulation (GVS) has a modulating effect on somatosensory perception and spatial cognition. However, other vestibular stimulation techniques have induced changes in affective control and decision making. The aim of this study was to investigate the effect of GVS on framing susceptibility in a risky-choice game. The participants were to decide between a safe and a risky option. The safe option was framed either positively or negatively. During the task, the participants were exposed to either left anodal/right cathodal GVS, right anodal/left cathodal GVS, or sham stimulation (control condition). While left anodal/right cathodal GVS activated more right-hemispheric vestibular brain areas, right anodal/left cathodal GVS resulted in more bilateral activation. We observed increased framing susceptibility during left anodal/right cathodal GVS, but no change in framing susceptibility during right anodal/left cathodal GVS. We propo...
Cerebral cortex (New York, N.Y. : 1991), Jan 23, 2016
With a reduced level of alertness, healthy individuals typically show a rightward shift when depl... more With a reduced level of alertness, healthy individuals typically show a rightward shift when deploying visual attention in space. The impact of alertness on the neural networks governing visuospatial attention is, however, poorly understood. By using a transcranial magnetic stimulation twin-coil approach, the present study aimed at investigating the effects of an alertness manipulation on the excitability of the left and the right posterior parietal cortices (PPCs), crucial nodes of the visuospatial attentional network. Participants' visuospatial attentional deployment was assessed with a free visual exploration task and concurrent eye tracking. Their alertness level was manipulated through the time of the day, that is, by testing chronotypically defined evening types both during their circadian on- and off-peak times. The results revealed an increased excitability of the left compared with the right PPC during low alertness. On the horizontal dimension, these results were accom...
Background/Aim: Gesturing plays an important role in social behavior and social learning. Deficit... more Background/Aim: Gesturing plays an important role in social behavior and social learning. Deficits are frequent in schizophrenia and may contribute to impaired social functioning. Information about deficits during the course of the disease and presence of severity and patterns of impairment in first-episode patients is missing. Hence, we aimed to investigate gesturing in first- compared to multiple-episode schizophrenia patients and healthy controls. Methods: In 14 first-episode patients, 14 multiple-episode patients and 16 healthy controls matched for age, gender and education, gesturing was assessed by the comprehensive Test of Upper Limb Apraxia. Performance in two domains of gesturing - imitation and pantomime - was recorded on video. Raters of gesture performance were blinded. Results: Patients with multiple episodes had severe gestural deficits. For almost all gesture categories, performance was worse in multiple- than in first-episode patients. First-episode patients demonstr...
Introduction: The neural correlates of impaired performance of gestures are currently unclear. Le... more Introduction: The neural correlates of impaired performance of gestures are currently unclear. Lesion studies showed variable involvement of the ventro-dorsal stream particularly left inferior frontal gyrus (IFG) in gesture performance on command. However, findings cannot be easily generalized as lesions may be biased by the architecture of vascular supply and involve brain areas beyond the critical region. The neuropsychiatric syndrome of schizophrenia shares apraxic-like errors and altered brain structure without macroanatomic lesions. Schizophrenia may therefore qualify as a model disorder to test neural correlates of gesture impairments. Methods: We included 45 schizophrenia patients and 44 healthy controls in the study to investigate the structural brain correlates of defective gesturing in schizophrenia using voxel based morphometry. Gestures were tested in two domains: meaningful gestures (transitive and intransitive) on verbal command and imitation of meaningless gestures. Cutoff scores were used to separate patients with deficits, patients without deficits and controls. Group differences in GM volume were explored in an ANCOVA. Results: Patients performed poorer than controls in each gesture category (p < 0.001). Patients with deficits in producing meaningful gestures on command had reduced gray matter (GM) predominantly in left IFG, with additional involvement of right insula and anterior cingulate cortex. Patients with deficits differed from patients without deficits in right insula, inferior parietal lobe and superior temporal gyrus. Conclusions: Impaired performance of meaningful gestures on command was linked to volume loss predominantly in the praxis network in schizophrenia. Thus, the behavioral similarities between apraxia and schizophrenia are paralleled by structural alterations.
We aimed at further elucidating whether aphasic patients' difficulties in understanding non-c... more We aimed at further elucidating whether aphasic patients' difficulties in understanding non-canonical sentence structures, such as Passive or Object-Verb-Subject sentences, can be attributed to impaired morphosyntactic cue recognition, and to problems in integrating competing interpretations. A sentence-picture matching task with canonical and non-canonical spoken sentences was performed using concurrent eye tracking. Accuracy, reaction time, and eye tracking data (fixations) of 50 healthy subjects and 12 aphasic patients were analysed. Patients showed increased error rates and reaction times, as well as delayed fixation preferences for target pictures in non-canonical sentences. Patients' fixation patterns differed from healthy controls and revealed deficits in recognizing and immediately integrating morphosyntactic cues. Our study corroborates the notion that difficulties in understanding syntactically complex sentences are attributable to a processing deficit encompassing...
BACKGROUND In a high proportion of patients with favorable outcome after aneurysmal subarachnoid ... more BACKGROUND In a high proportion of patients with favorable outcome after aneurysmal subarachnoid hemorrhage (aSAH), neuropsychological deficits, depression, anxiety, and fatigue are responsible for the inability to return to their regular premorbid life and pursue their professional careers. These problems often remain unrecognized, as no recommendations concerning a standardized comprehensive assessment have yet found entry into clinical routines. METHODS To establish a nationwide standard concerning a comprehensive assessment after aSAH, representatives of all neuropsychological and neurosurgical departments of those eight Swiss centers treating acute aSAH have agreed on a common protocol. In addition, a battery of questionnaires and neuropsychological tests was selected, optimally suited to the deficits found most prevalent in aSAH patients that was available in different languages and standardized. RESULTS We propose a baseline inpatient neuropsychological screening using the Montreal Cognitive Assessment (MoCA) between days 14 and 28 after aSAH. In an outpatient setting at 3 and 12 months after bleeding, we recommend a neuropsychological examination, testing all relevant domains including attention, speed of information processing, executive functions, verbal and visual learning/memory, language, visuo-perceptual abilities, and premorbid intelligence. In addition, a detailed assessment capturing anxiety, depression, fatigue, symptoms of frontal lobe affection, and quality of life should be performed. CONCLUSIONS This standardized neuropsychological assessment will lead to a more comprehensive assessment of the patient, facilitate the detection and subsequent treatment of previously unrecognized but relevant impairments, and help to determine the incidence, characteristics, modifiable risk factors, and the clinical course of these impairments after aSAH.The need for clinically applicable skin substitutes continues to be a matter of fact. Hypothetically, a laboratory grown autologous skin analog with near normal architecture might be a suitable approach to yield both satisfactory functional and cosmetic long-term results. In this study, we explored the use of human endothelial cells derived from freshly isolated adipose stromal vascular fraction (SVF) in a three-dimensional (3D) coculture model of vascularized bio-engineered skin substitute. METHODS The SVF was isolated from human white adipose tissue samples and keratinocytes from human skin biopsies. The SVF, in particular endothelial cells, were characterized using flow cytometry and immuofluorescence analysis. Endothelial and mesenchymal progenitors from the SVF formed blood capillaries after seeding into a 3D collagen type I hydrogel in vitro. Subsequently, human keratinocytes were seeded on the top of those hydrogels to develop a vascularized dermo-epidermal skin substitute. RESULTS Flow cytometric analysis of surface markers of the freshly isolated SVF showed the expression of endothelial markers (CD31, CD34, CD146), mesenchymal/stromal cell-associated markers (CD44, CD73, CD90, CD105), stem cell markers (CD49f, CD117, CD133), and additionally hematopoietic markers (CD14, CD15, CD45). Further analysis of white adipose-derived endothelial cells (watECs) revealed the co-expression of CD31, CD34, CD90, CD105, and partially CD146 on these cells. WatECs were separated from adipose-stromal cells (watASCs) using FACS sorting. WatASCs and watECs cultured separately in a 3D hydrogel for 3 weeks did not form any vascular structures. Only if co-cultured, both cell types aligned to develop a ramified vascular network in vitro with continuous endothelial lumen formation. Transplantation of those 3D-hydrogels onto immuno-incompetent rats resulted in a rapid connection of human capillaries with the host vessels and formation of functional, blood-perfused mosaic human-rat vessels within only 3-4 days. CONCLUSIONS Adipose tissue represents an attractive cell source due to the ease of isolation and abundance of endothelial as well as mesenchymal cell lineages. Adipose-derived SVF cells exhibit the ability to form microvascular structures in vitro and support the accelerated blood perfusion in skin substitutes in vivo when transplanted.
Converging evidences from eye movement experiments indicate that linguistic contexts influence re... more Converging evidences from eye movement experiments indicate that linguistic contexts influence reading strategies. However, the question of whether different linguistic contexts modulate eye movements during reading in the same bilingual individuals remains unresolved. We examined reading strategies in a transparent (German) and an opaque (French) language of early, highly proficient French–German bilinguals: participants read aloud isolated French and German words and pseudo-words while the First Fixation Location (FFL), its duration and latency were measured. Since transparent linguistic contexts and pseudo-words would favour a direct grapheme/phoneme conversion, the reading strategy should be more local for German than for French words (FFL closer to the beginning) and no difference is expected in pseudo-words’ FFL between contexts. Our results confirm these hypotheses, providing the first evidence that the same individuals engage different reading strategy depending on language ...
Aphasia is a common syndrome after left-lateralized stroke and is characterized by partial or tot... more Aphasia is a common syndrome after left-lateralized stroke and is characterized by partial or total loss of language functions. Functional imaging studies examining language recovery after stroke often find an overactivation of the non-damaged right hemisphere. One hypothesis is that the overactivation is dysfunctional which is explained within the framework of interhemispheric inhibition. Non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) allow modulating cortical activity and may thereby offer novel therapeutic opportunities. A repetitive TMS protocol named theta burst stimulation (TBS) is increasingly used in clinical research. It has the advantage of a short application time combined with prolonged aftereffects. In a previous study we found better naming performance in aphasic patients after the application of one train of TBS over the right Broca's homologue. Applying TBS trains repeatedly can furthermore disproportionately prolong the effects, as was for example shown in neglect patients. Thus, repeated trains of TBS are applied in the present study in a randomized, sham controlled, cross-over design. After comprehensive baseline testing, eight TBS trains and eight sham stimulation trains are applied over the right Broca's homologue on two consecutive days separated by one week. On the second days of stimulation, several short language tests are administered. A follow-up with comprehensive language testing takes place one month after the stimulation. Preliminary results of this ongoing study will be presented. The aim of the study is to evaluate the effects of repeated TBS on several language tasks over a longer time span.
This study investigated the roles of the right and left dorsolateral prefrontal (rDLPFC, lDLPFC) ... more This study investigated the roles of the right and left dorsolateral prefrontal (rDLPFC, lDLPFC) and the medial frontal cortex (MFC) in executive functioning using a theta burst transcranial magnetic stimulation (TMS) approach. Healthy subjects solved two visual search tasks: a number search task with low cognitive demands, and a number and letter search task with high cognitive demands. To observe how subjects solved the tasks, we assessed their behavior with and without TMS using eye movements when subjects were confronted with specific executive demands. To observe executive functions, we were particularly interested in TMS-induced changes in visual exploration strategies found to be associated with good or bad performance in a control condition without TMS stimulation. TMS left processing time unchanged in both tasks. Inhibition of the rDLPFC resulted in a decrease in anticipatory fixations in the number search task, i.e., a decrease in a good strategy in this low demand task. This was paired with a decrease in stimulus fixations. Together, these results point to a role of the rDLPFC in planning and response selection. Inhibition of the lDLPFC and the MFC resulted in an increase in anticipatory fixations in the number and letter search task, i.e., an increase in the application of a good strategy in this task. We interpret these results as a compensatory strategy to account for TMS-induced deficits in attentional switching when faced with high switching demands. After inhibition of the lDLPFC, an increase in regressive fixations was found in the number and letter search task. In the context of high working memory demands, this strategy appears to support TMS-induced working memory deficits. Combining an experimental TMS approach with the recording of eye movements proved sensitive to discrete decrements of executive functions and allows pinpointing the functional organization of the frontal lobes.
Previous work has reported that in the Iowa gambling task (IGT) advantageous decisions may be tak... more Previous work has reported that in the Iowa gambling task (IGT) advantageous decisions may be taken before the advantageous strategy is known [Bechara, A., Damasio, H., Tranel, D., &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp; Damasio, A. R. (1997). Deciding advantageously before knowing the advantageous strategy. Science, 275, 1293-1295]. In order to test whether explicit memory is essential for the acquisition of a behavioural preference for advantageous choices, we measured behavioural performance and skin conductance responses (SCRs) in five patients with dense amnesia following damage to the basal forebrain and orbitofrontal cortex, six amnesic patients with damage to the medial temporal lobe or the diencephalon, and eight control subjects performing the IGT. Across 100 trials healthy participants acquired a preference for advantageous choices and generated large SCRs to high levels of punishment. In addition, their anticipatory SCRs to disadvantageous choices were larger than to advantageous choices. However, this dissociation occurred much later than the behavioural preference for advantageous alternatives. In contrast, though exhibiting discriminatory autonomic SCRs to different levels of punishment, 9 of 11 amnesic patients performed at chance and did not show differential anticipatory SCRs to advantageous and disadvantageous choices. Further, the magnitude of anticipatory SCRs did not correlate with behavioural performance. These results suggest that the acquisition of a behavioural preference--be it for advantageous or disadvantageous choices--depends on the memory of previous reinforcements encountered in the task, a capacity requiring intact explicit memory.
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Papers by René Müri