Screening for language disorders in stroke: german validation of the language screening test (last)

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

Steroid hormone bioavailability is controlled by the lymphatic system.

The steroid hormone progesterone accounts for immune tolerance in pregnancy. Enhanced progesterone metabolism to 6α-OH-pregnanolone occurs in complicated pregnancies such as in preeclampsia with preterm delivery or intrauterine growth restriction, and in cancer. As lymphatic endothelial cells (LECs) promote tumor immunity, we hypothesized that human LECs modify progesterone bioavailability. Primary human LECs and mice lymph nodes were incubated with progesterone and progesterone metabolism was analyzed by thin layer chromatography and liquid chromatography-mass spectrometry. Expression of steroidogenic enzymes, down-stream signal and steroid hormone receptors was assessed by Real-time PCR. The placental cell line HTR-8/SV neo was used as reference. The impact of the progesterone metabolites of interest was investigated on the immune system by fluorescence-activated cell sorting analysis. LECs metabolize progesterone to 6α-OH-pregnanolone and reactivate progesterone from a precursor. LECs highly express 17β-hydroxysteroid dehydrogenase 2 and are therefore antiandrogenic and antiestrogenic. LECs express several steroid hormone receptors and PIBF1. Progesterone and its metabolites reduced TNF-α and IFN-γ production in CD4+ and CD8+ T cells. LECs modify progesterone bioavailability and are a target of steroid hormones. Given the global area represented by LECs, they might have a critical immunomodulatory control in pregnancy and cancer

The modulation of reading strategies by language opacity in early bilinguals: an eye movement study

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 opacity, suggesting that a given brain process can be modulated by a given context

Perception of co-speech gestures in aphasic patients: A visual exploration study during the observation of dyadic conversations

Co-speech gestures are part of nonverbal communication during conversations. They either support the verbal message or provide the interlocutor with additional information. Furthermore, they prompt as nonverbal cues the cooperative process of turn taking. In the present study, we investigated the influence of co-speech gestures on the perception of dyadic dialogue in aphasic patients. In particular, we analysed the impact of co-speech gestures on gaze direction (towards speaker or listener) and fixation of body parts. We hypothesized that aphasic patients, who are restricted in verbal comprehension, adapt their visual exploration strategies.Methods: Sixteen aphasic patients and 23 healthy control subjects participated in the study. Visual exploration behaviour was measured by means of a contact-free infrared eye-tracker while subjects were watching videos depicting spontaneous dialogues between two individuals. Cumulative fixation duration and mean fixation duration were calculated for the factors co-speech gesture (present and absent), gaze direction (to the speaker or to the listener), and region of interest (ROI), including hands, face, and body.Results: Both aphasic patients and healthy controls mainly fixated the speaker's face. We found a significant co-speech gesture × ROI interaction, indicating that the presence of a co-speech gesture encouraged subjects to look at the speaker. Further, there was a significant gaze direction × ROI × group interaction revealing that aphasic patients showed reduced cumulative fixation duration on the speaker's face compared to healthy controls.Conclusion: Co-speech gestures guide the observer's attention towards the speaker, the source of semantic input. It is discussed whether an underlying semantic processing deficit or a deficit to integrate audio-visual information may cause aphasic patients to explore less the speaker's face

Theta burst stimulation reduces disability during the activities of daily living in spatial neglect

Left-sided spatial neglect is a common neurological syndrome following right-hemispheric stroke. The presence of spatial neglect is a powerful predictor of poor rehabilitation outcome. In one influential account of spatial neglect, interhemispheric inhibition is impaired and leads to a pathological hyperactivity in the contralesional hemisphere, resulting in a biased attentional allocation towards the right hemifield. Inhibitory transcranial magnetic stimulation can reduce the hyperactivity of the contralesional, intact hemisphere and thereby improve spatial neglect symptoms. However, it is not known whether this improvement is also relevant to the activities of daily living during spontaneous behaviour. The primary aim of the present study was to investigate whether the repeated application of continuous theta burst stimulation trains could ameliorate spatial neglect on a quantitative measure of the activities of daily living during spontaneous behaviour. We applied the Catherine Bergego Scale, a standardized observation questionnaire that can validly and reliably detect the presence and severity of spatial neglect during the activities of daily living. Eight trains of continuous theta burst stimulation were applied over two consecutive days on the contralesional, left posterior parietal cortex in patients suffering from subacute left spatial neglect, in a randomized, double-blind, sham-controlled design, which also included a control group of neglect patients without stimulation. The results showed a 37% improvement in the spontaneous everyday behaviour of the neglect patients after the repeated application of continuous theta burst stimulation. Remarkably, the improvement persisted for at least 3 weeks after stimulation. The amelioration of spatial neglect symptoms in the activities of daily living was also generally accompanied by significantly better performance in the neuropsychological tests. No significant amelioration in symptoms was observed after sham stimulation or in the control group without stimulation. These results provide Class I evidence that continuous theta burst stimulation is a viable add-on therapy in neglect rehabilitation that facilitates recovery of normal everyday behaviou

Comprehension of co-speech gestures in aphasic patients: an eye movement study

Co-speech gestures are omnipresent and a crucial element of human interaction by facilitating language comprehension. However, it is unclear whether gestures also support language comprehension in aphasic patients. Using visual exploration behavior analysis, the present study aimed to investigate the influence of congruence between speech and co-speech gestures on comprehension in terms of accuracy in a decision task.Method: Twenty aphasic patients and 30 healthy controls watched videos in which speech was either combined with meaningless (baseline condition), congruent, or incongruent gestures. Comprehension was assessed with a decision task, while remote eye-tracking allowed analysis of visual exploration.Results: In aphasic patients, the incongruent condition resulted in a significant decrease of accuracy, while the congruent condition led to a significant increase in accuracy compared to baseline accuracy. In the control group, the incongruent condition resulted in a decrease in accuracy, while the congruent condition did not significantly increase the accuracy. Visual exploration analysis showed that patients fixated significantly less on the face and tended to fixate more on the gesturing hands compared to controls.Conclusion: Co-speech gestures play an important role for aphasic patients as they modulate comprehension. Incongruent gestures evoke significant interference and deteriorate patients’ comprehension. In contrast, congruent gestures enhance comprehension in aphasic patients, which might be valuable for clinical and therapeutic purposes

Theta burst stimulation reduces disability during the activities of daily living in spatial neglect

Left-sided spatial neglect is a common neurological syndrome following right-hemispheric stroke. The presence of spatial neglect is a powerful predictor of poor rehabilitation outcome. In one influential account of spatial neglect, interhemispheric inhibition is impaired and leads to a pathological hyperactivity in the contralesional hemisphere, resulting in a biased attentional allocation towards the right hemifield. Inhibitory transcranial magnetic stimulation can reduce the hyperactivity of the contralesional, intact hemisphere and thereby improve spatial neglect symptoms. However, it is not known whether this improvement is also relevant to the activities of daily living during spontaneous behaviour. The primary aim of the present study was to investigate whether the repeated application of continuous theta burst stimulation trains could ameliorate spatial neglect on a quantitative measure of the activities of daily living during spontaneous behaviour. We applied the Catherine Bergego Scale, a standardized observation questionnaire that can validly and reliably detect the presence and severity of spatial neglect during the activities of daily living. Eight trains of continuous theta burst stimulation were applied over two consecutive days on the contralesional, left posterior parietal cortex in patients suffering from subacute left spatial neglect, in a randomized, double-blind, sham-controlled design, which also included a control group of neglect patients without stimulation. The results showed a 37% improvement in the spontaneous everyday behaviour of the neglect patients after the repeated application of continuous theta burst stimulation. Remarkably, the improvement persisted for at least 3 weeks after stimulation. The amelioration of spatial neglect symptoms in the activities of daily living was also generally accompanied by significantly better performance in the neuropsychological tests. No significant amelioration in symptoms was observed after sham stimulation or in the control group without stimulation. These results provide Class I evidence that continuous theta burst stimulation is a viable add-on therapy in neglect rehabilitation that facilitates recovery of normal everyday behaviour

Treatment response of advanced HNSCC towards immune checkpoint inhibition is associated with an activated effector memory T cell phenotype

Locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with a poor prognosis. The introduction of PD-1 inhibitors has led to a significant improvement in survival, but only a subpopulation of patients responds to therapy. Current biomarkers cannot reliably identify these patients. The identification of biomarkers for the prediction and monitoring of immunotherapy is therefore of great importance. In this study, we characterized lymphocyte subsets in the peripheral blood of HNSCC patients under PD-1 inhibition. Patients with primary response (n=11) to PD-1 inhibition showed an increase of the CD3+ effector memory (CD3/EM) population and an elevated expression of the activation marker CD69 in CD3+ T cells, particularly in the CD3/EM subpopulation at 3 months when treatment response was assessed. In contrast, patients with primary treatment failure and progressive disease (n=9) despite PD-1 inhibition had lower absolute lymphocyte counts and an increased expression of CTLA-4 in CD3+ T cells at the time of treatment failure compared with baseline, particularly in CD4+ and CD8+ effector memory populations. Our results demonstrate that HNSCC patients’ response to immune checkpoint inhibition shows a distinct immune signature in peripheral blood, which could help identify refractory patients earlier. Furthermore, strategies to overcome primary therapy failure by inducing a beneficial T cell phenotype or adding alternative immune checkpoint inhibitors could improve response rates and survival of HNSCC patients

Assessing and mapping language, attention and executive multidimensional deficits in stroke aphasia.

There is growing awareness that aphasia following a stroke can include deficits in other cognitive functions and that these are predictive of certain aspects of language function, recovery and rehabilitation. However, data on attentional and executive (dys)functions in individuals with stroke aphasia are still scarce and the relationship to underlying lesions is rarely explored. Accordingly in this investigation, an extensive selection of standardized non-verbal neuropsychological tests was administered to 38 individuals with chronic post-stroke aphasia, in addition to detailed language testing and MRI. To establish the core components underlying the variable patients' performance, behavioural data were explored with rotated principal component analyses, first separately for the non-verbal and language tests, then in a combined analysis including all tests. Three orthogonal components for the non-verbal tests were extracted, which were interpreted as shift-update, inhibit-generate and speed. Three components were also extracted for the language tests, representing phonology, semantics and speech quanta. Individual continuous scores on each component were then included in a voxel-based correlational methodology analysis, yielding significant clusters for all components. The shift-update component was associated with a posterior left temporo-occipital and bilateral medial parietal cluster, the inhibit-generate component was mainly associated with left frontal and bilateral medial frontal regions, and the speed component with several small right-sided fronto-parieto-occipital clusters. Two complementary multivariate brain-behaviour mapping methods were also used, which showed converging results. Together the results suggest that a range of brain regions are involved in attention and executive functioning, and that these non-language domains play a role in the abilities of patients with chronic aphasia. In conclusion, our findings confirm and extend our understanding of the multidimensionality of stroke aphasia, emphasize the importance of assessing non-verbal cognition in this patient group and provide directions for future research and clinical practice. We also briefly compare and discuss univariate and multivariate methods for brain-behaviour mapping