Neurophysiological processes reflecting the effects of the immediate past during the dynamic management of actions.

In recent years, there has been many efforts to establish a comprehensive theoretical framework explaining the working mechanisms involved in perception-action integration. This framework stresses the importance of the immediate past on mechanisms supporting perception-action integration. The present study investigates the neurophysiological principles of dynamic perception-action bindings, particularly considering the influence of the immediate history on action control mechanisms. For this purpose, we conducted an established stimulus-response binding paradigm during EEG recording. The SR-task measures stimulus-response binding in terms of accuracy and reaction time differences depending on the degree of feature overlap between conditions. Alpha, beta and theta band activity in distinct time domains as well as associated brain regions were investigated applying time-frequency analyses, a beamforming approach as well as correlation analyses. We demonstrate, for the first time, interdependencies of neuronal processes relying on the immediate past. The reconfiguration of an action seems to overwrite immediately preceding processes. The analyses revealed modulations of theta (TBA), alpha (ABA) and beta band activity (BBA) in connection with fronto-temporal structures supporting the theoretical assumptions of the considered conceptual framework. The close interplay of attentional modulation by gating irrelevant information (ABA) and binding and retrieval processes (TBA) is reflected by the correlation of ABA in all pre-probe-intervals with post-probe TBA. Likewise, the role of BBA in maintaining the event file until retrieval is corroborated by BBA preceding the TBA-associated retrieval of perception-action codes. Following action execution, TBA shifted towards visual association cortices probably reflecting preparation for upcoming information, while ABA and BBA continue to reflect processes of attentional control and information selection for goal-directed behavior. The present work provides the first empirical support for concepts about the neurophysiological mechanisms of dynamic management of perception and action.

Accelerated corneal cross-linking (18mW/cm2 for 5 min) with HPMC-riboflavin in progressive keratoconus - 5 years follow-up.

PURPOSE: To evaluate long-term results of accelerated corneal cross-linking (ACXL) in patients with progressive keratoconus, seventy-four eyes of 53 patients with progressive keratoconus (documented Kmax progression > 1D/a) who underwent ACXL (18mW/cm2 for 5 min) were included in a retrospective observational clinical study. The investigation focused on tomographic and keratometric parameters, refractive data, and visual outcomes at 5 years follow-ups. METHODS: Corrected distance visual acuity (CDVA), slit lamp, and Pentacam® examinations were conducted, including assessments of thinnest corneal point (TP), minimum radius (Rmin), corneal astigmatism, and maximum anterior keratometry (Kmax). These examinations were performed two weeks before the surgery and, on average, 56 months after the surgery. In a subgroup of 24 eyes, Pentacam® examination data from an intermediate visit at 12 months until the final visit was evaluated to confirm continuous stability. The ACXL protocol included corneal abrasion, hydroxypropylmethylcellulose (HPMC)-riboflavin eye drops administered every 5 min for a total duration of 30 min, and irradiation with 18mW/cm2 for 5 min using riboflavin eye drops applied every minute during the irradiation process. Intraoperatively, minimal corneal pachymetry of > 400 µm was ensured in every patient. RESULTS: After 56 months, all values exhibited statistically significant changes (paired t-test; CDVA p = 0.002; Kmax p < 0.001; Rmin p < 0.001; astigmatism p = 0.03; TP p < 0.001). In the subgroup analysis of 24 eyes, which included tomographical and keratometric parameters, no statistically significant changes were observed during the last 12 months of observation (paired t-test; Kmax p = 0.72; Rmin p = 0.67; astigmatism p = 0.72). Treatment failure was strictly defined as an increase in Kmax (> 1D) during the 5-year follow-up and was observed in only 3 eyes (4%). CONCLUSIONS: ACXL is an effective and safe treatment for patients with progressive keratoconus. Our results demonstrate improvements in functional and tomographical outcomes even after high-energy ACXL (18mW/cm2 for 5 min) over a long-term period of 56 months. Our analysis indicates stable conditions in previously progressive keratoconus, particularly during the final year of the observation period. The treatment failure rate was 4%.

Perception-Action Integration Is Altered in Functional Movement Disorders.

BACKGROUND: Although functional neurological movement disorders (FMD) are characterized by motor symptoms, sensory processing has also been shown to be disturbed. However, how the integration of perception and motor processes, essential for the control of goal-directed behavior, is altered in patients with FMD is less clear. A detailed investigation of these processes is crucial to foster a better understanding of the pathophysiology of FMD and can systematically be achieved in the framework of the theory of event coding (TEC). OBJECTIVE: The aim was to investigate perception-action integration processes on a behavioral and neurophysiological level in patients with FMD. METHODS: A total of 21 patients and 21 controls were investigated with a TEC-related task, including concomitant electroencephalogram (EEG) recording. We focused on EEG correlates established to reflect perception-action integration processes. Temporal decomposition allowed to distinguish between EEG codes reflecting sensory (S-cluster), motor (R-cluster), and integrated sensory-motor processing (C-cluster). We also applied source localization analyses. RESULTS: Behaviorally, patients revealed stronger binding between perception and action, as evidenced by difficulties in reconfiguring previously established stimulus-response associations. Such hyperbinding was paralleled by a modulation of neuronal activity clusters, including reduced C-cluster modulations of the inferior parietal cortex and altered R-cluster modulations in the inferior frontal gyrus. Correlations of these modulations with symptom severity were also evident. CONCLUSIONS: Our study shows that FMD is characterized by altered integration of sensory information with motor processes. Relations between clinical severity and both behavioral performance and neurophysiological abnormalities indicate that perception-action integration processes are central and a promising concept for the understanding of FMD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Visual improvement and regeneration of retinal layers in eyes with small, medium, and large idiopathic full-thickness macular holes treated with the inverted internal limiting membrane flap technique over a period of 12 months.

PURPOSE: This study aims to compare the improvement of best-corrected visual acuity (BCVA) and the reduction in defect length of external limiting membrane (ELM) and ellipsoid zone (EZ) in small ([Formula: see text] 250 µm), medium ([Formula: see text] 250 µm), and large ([Formula: see text] 400 µm) full-thickness macular holes (FTMH) treated with inverted internal limiting membrane (I-ILM) flap technique over a follow-up period of 12 months. METHODS: Ninety-one eyes of 87 patients were enrolled in this retrospective study. BCVA and spectral-domain optical coherence tomography (SD-OCT) were conducted preoperatively as well as after 1, 3, 6, 9, and 12 months postoperatively. The defect length of the ELM and the EZ was measured using the caliper tool at each follow-up time point. RESULTS: BCVA improved significantly in the group of small, medium, and large FTMH over the time of 12 months, whereby the improvement did not depend on FTMH size over 9 months. Only after 12 months, large FTMH showed significantly higher BCVA improvement compared to small and medium FTMH. The closure rate was 100% (91/91). The defect length of ELM and EZ reduced continuously over the period of 12 months. There was a significant correlation between defect length of ELM and EZ with postoperative BCVA. CONCLUSION: The I-ILM flap technique has very good morphological and functional outcomes in small, medium, and large FTMH over a long-time period, indicating that it can be considered as a treatment option in small and medium FTMH. The defect length of ELM and EZ is directly connected to postoperative BCVA.

Preschoolers agree to and enforce prosocial, but not selfish, sharing norms.

Young children act prosocially in many contexts but are somewhat selfish when it comes to sharing their resources in individual decision-making situations (e.g., the dictator game). But when deciding collectively, would they make it a binding rule for themselves and others to act selfishly in a resource sharing context? Here we used a novel "group dictator game" in a norm creation paradigm to investigate whether 3- and 5-year-olds (N = 48) would agree to and enforce a selfish or prosocial sharing norm. Children from a Western cultural background were paired with two puppets at a time. Each group member had an endowment of four stickers and faced a photograph of a recipient. In the prosocial norm condition a proposer puppet suggested to share half of one's endowment, whereas in the selfish norm condition another proposer suggested to share nothing. The protagonist puppet then either followed or violated the suggested norm. We found that 5-year-olds (but not 3-year-olds) rejected selfish proposals more often than prosocial proposals. Importantly, older (but not younger) preschoolers also enforced the prosocial (but not the selfish) norm by protesting normatively and intervening when the protagonist acted selfishly (and thus violated the norm). These results indicate that a collective decision-making context may enhance preschoolers' prosociality and that moral considerations on the content of a proposed sharing rule influence preschoolers' creation and enforcement of such nonarbitrary norms.

Functional recovery after macula involving retinal detachment and its correlation with preoperative biomarkers in optical coherence tomography.

To introduce an ETDRS grid-based classification for macula involving retinal detachment (MIRD) with or without center (foveal) involvement and to identify biomarkers in preoperative optical coherence tomography (OCT) associated with a favorable postoperative functional outcome in eyes with center involving retinal detachment (CIRD). One hundred and two eyes of 102 consecutive patients (f/m: 35/67) with primary rhegmatogenous retinal detachment, preoperative evidence of MIRD (perifoveal involvement of ≤ 6.0 mm), and successful retinal surgery were included in this retrospective cohort study. Eyes were assigned to 5 grades of MIRD (G1-G5), based on the extent of detachment in the ETDRS grid. Eyes with a detached foveal status (CIRD) were assigned to G4 or G5. In CIRD, the following OCT biomarkers were quantified and correlated with mean BCVA (logMAR) at 3 months postsurgery, using univariate and multivariable regression models: grade of detachment, extent of intraretinal edema, height of foveal detachment, subretinal folds, and epiretinal membrane. Forty-one of 102 eyes (40.2%) presented with an attached foveal status, defined as either outer (G1: 11.8%) or inner (G2: 18.6%) macular involvement or fovea-threatening MIRD (G3: 9.8%). Sixty-one eyes (59.8%) showed CIRD (G4 or G5). Eyes with CIRD had significantly worse postoperative BCVA than eyes without foveal involvement (0.355 logMAR vs. 0.138 logMAR, p<0.001). If CIRD was limited to three outer ETDRS quadrants (G4), mean BCVA was better compared to CIRD involving all four ETDRS quadrants (G5) (0.254 logMAR vs. 0.522 logMAR, p<0.001). Reading ability (BCVA ≤ 0.4 logMAR) was restored in 97.6% of eyes with G1-G3 compared to 86.9% of eyes with G4 (p=0.072) and 52.4% of eyes with G5 (p<0.001). In multivariable regression analysis of eyes with CIRD, a lower grade of detachment (G4 vs. G5: p<0.05) and lower extent of cystoid edema (focal/none vs. wide: p<0.001) were both associated with better postoperative function. The functional outcome after MIRD may be worse in the presence of foveal involvement (CIRD), but a lower grade of detachment and the absence of intraretinal edema can predict a good recovery in spite of CIRD.

Inverted internal limiting membrane flap technique in eyes with large idiopathic full-thickness macular hole: long-term functional and morphological outcomes.

PURPOSE: To investigate morphological and functional outcomes of the inverted internal limiting membrane (I-ILM) flap technique in large (≥ 400 µm) idiopathic full-thickness macular holes (FTMH) over a follow-up period of 12 months. METHODS: In this retrospective study, 55 eyes of 54 consecutive patients were enrolled. Best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (SD-OCT, Heidelberg, Spectralis) were performed preoperatively as well as 1, 3, 6, 9, and 12 months postoperatively. Special focus was put on the reintegration of outer retinal layers and the different ILM flap appearances. RESULTS: FTMH closure rate was 100% (55/55). BCVA significantly improved over the follow-up period of 12 months from 0.98 ± 0.38 LogMAR preoperatively to 0.42 ± 0.33 LogMAR at 12 months postoperatively (p < 0.001). There was no significant correlation between the three different ILM flap appearances and BCVA. Better preoperative BCVA, complete restoration of the external limiting membrane (ELM), higher macular hole index (MHI), and smaller MH base diameter were associated with higher improvement of BCVA. CONCLUSION: Our study highlights the favorable morphological and functional outcomes of the I-ILM flap technique in the short as well as in the long term. While complete ELM restoration revealed to be an important factor for improvement in BCVA, the different postoperative ILM flap appearances seem not to be related to BCVA.

Passive perceptual learning modulates motor inhibitory control in superior frontal regions.

Response inhibition is of vital importance in the context of controlling inappropriate responses. The role of perceptual processes during inhibitory control has attracted increased interest. Yet, we are far from an understanding of the mechanisms. One candidate mechanism by which perceptual processes may affect response inhibition refers to "gain control" that is closely linked to the signal-to-noise ratio of incoming information. A means to modulate the signal-to-noise ratio and gain control mechanisms is perceptual learning. In the current study, we examine the impact of perceptual learning (i.e., passive repetitive sensory stimulation) on response inhibition combining EEG signal decomposition with source localization analyses. A tactile GO/NOGO paradigm was conducted to measure action restraint as one subcomponent of response inhibition. We show that passive perceptual learning modulates response inhibition processes. In particular, perceptual learning attenuates the detrimental effect of response automation during inhibitory control. Temporally decomposed EEG data show that stimulus-related and not response selection processes during conflict monitoring are linked to these effects. The superior and middle frontal gyrus (BA6), as well as the motor cortex (BA4), are associated with the effects of perceptual learning on response inhibition. Reliable neurophysiological effects were not evident on the basis of standard ERPs, which has important methodological implications for perceptual learning research. The results detail how lower level sensory plasticity protocols affect higher-order cognitive control functions in frontal cortical structures.

Neurofeedback trains a superordinate system relevant for seemingly opposing behavioral control deficits depending on ADHD subtype.

ADHD is one of the most prevalent neuropsychiatric disorders of childhood, but symptoms vary considerably between individuals. Therefore, different ADHD subtypes can be distinguished. Yet, it is widely elusive whether the specific subtype is critical to consider when examining treatment effects. Based on theoretical considerations, this could be the case for EEG theta/beta neurofeedback. We examine the effects of such an intervention on rapid response execution and inhibition processes using a Go/Nogo task in the inattentive (ADD) and the combined (ADHD-C) subtype. We show that a single neurofeedback protocol affects opposing deficits depending on the ADHD subtype - namely the execution (in ADD) and inhibition of action (in ADHD-C). No changes occurred in the healthy controls. These findings are discussed in relation to overarching principles of neural oscillations, particularly in the beta frequency band. The data suggest that theta/beta neurofeedback trains a superordinate system strongly related to the function of neural beta frequency oscillations to tune neural networks important for the sampling of sensory information used for behavioral control.

New infection rate of bovine mammary glands after application of an internal teat seal at dry-off.

The internal teat sealant OrbeSeal® (Zoetis, Berlin, Germany) is intended to prevent new intramammary infection (IMI) throughout the dry period. The aim of this field study was to determine new infection rates in udder quarters applied exclusively with the sealant at dry-off and untreated ones (control group). For that, the new infection rate of udder quarters treated with the sealant was evaluated in a split-udder design (front right and rear left udder quarters treated, the other ones untreated) in 128 cows from nine dairy farms in North Germany that were healthy in all four udder quarters (i.e. <100 000 cells/ml, bacteriologically negative). After calving, duplicate quarter milk samples were collected twice at DIM (days in milk) 5-12 and 7 d later for culture. The new infection rates for treated and untreated groups were 3·4 and 10·5%, respectively. The results showed that applying a standardised study design with very few confounders under field conditions, using internal teat sealants reduced the new infection rate on quarter level to a third of that of the control group. Thus, internal teat sealants represent a viable option for dry-off treatment of udder-healthy cows.

Cognitive and Neural Mechanisms of Behavior Therapy for Tics: A Perception-Action Integration Approach.

European clinical guidelines recommend the use of Exposure and Response Prevention (ERP) and Comprehensive Behavioral Intervention for Tics (CBIT) as first-line treatments for tic disorders. Although ongoing efforts in research are being made to understand the mechanisms underlying these behavioral approaches, as of yet, the neurophysiological mechanisms behind behavioral interventions are poorly understood. However, this is essential to tailor interventions to individual patients in order to increase compliance and efficacy. The Theory of Event Coding (TEC) and its derivative BRAC (Binding and Retrieval in Action Control) provide a theoretical framework to investigate cognitive and neural processes in the context of tic disorders. In this context, tics are conceptualized as a phenomenon of enhanced perception-action binding, with premonitory urges constituting the perceptual and the motor or vocal expression constituting the action part of an event file. Based on this, CBIT is assumed to strongly affect stimulus-response binding in the context of response selection, whereas the effects of ERP presumably unfold during stimulus-response binding in the response inhibition context. Further studies are needed to clarify the neurophysiological processes underlying behavioral interventions to enable the individualization and further development of therapeutic approaches for tic disorders.

Personalized [177Lu]Lutetium-PSMA Therapy for Patients with Pre-Treated Castration-Resistant Prostate Cancer: A Single Institution Experience from a Comprehensive Cancer Centre.

Castration resistant prostate cancer (CRPC) is characterized by an aggressive biological behavior with a relatively short survival time, especially in progressive tumors pretreated with new hormonal agents and taxane chemotherapy. [177Lu]-Lutetium-PSMA (Lu-PSMA) treatment has proven efficacy in these patients. However, around 30% of the CRPC patients do not benefit from Lu-PSMA treatment, and little is known about predictive factors for treatment success if Lu-PSMA is offered in an individualized approach based on clinical and laboratory features. In this monocentric retrospective study, 86 CRPC patients receiving Lu-PSMA treatment were evaluated. The focus of the study was to describe clinical factors at baseline and during early treatment that are related to overall survival (OS). In addition, PSMA PET/CT-, PSA-response, and safety and tolerability (CTCAE adverse event reporting) were assessed. Efficacy endpoints were calculated using stratified Kaplan-Meier methods and Cox regression models. Mean applied dose was 17.7 GBq (mean 5.3 ± 1.1 GBq per cycle) with an average of 3.6 (range 1-8) therapy cycles. Patients were followed up for a mean of 12.4 months (range 1-39). The median OS was 15 months (95% CI 12.8-17.2). The best overall response rate in patients assessed with PSMA PET/CT and PSA response was 27.9%, and 50.0% had at least stable disease. Nine patients had a ≥grade 3 adverse event with anemia being the most frequent adverse event. Positive predictors for prolonged OS from baseline parameters were pre-treatment hemoglobin level of ≥10 g/dL and a lower PSA values at treatment start, while the presence of visceral or liver metastases were not significantly associated with worse prognoses in this cohort. With careful patient selection, an individualized Lu-PSMA treatment approach is feasible and patients with dose-limiting factors or visceral metastases should be included in prospective trials.

The Role of the Left Inferior Parietal Cortex in Gilles de la Tourette Syndrome-An rTMS Study.

Increased activity in the left inferior parietal cortex (BA40) plays a role in the generation of tics in the Gilles de la Tourette syndrome (GTS). Thus, inhibitory repetitive transcranial magnetic stimulation (rTMS) applied to BA40 was hypothesized to alleviate symptoms in GTS. We investigated the immediate effects of single-session 1 Hz rTMS and sham stimulation delivered to the left BA40 on tics assessed with the Rush video protocol in 29 adults with GTS. There were no significant effects on tic symptoms following rTMS or sham stimulation. Moreover, there was no difference when comparing the effects of both stimulation conditions. Bayesian statistics indicated substantial evidence against an intervention effect. The left BA40 appears not to be a useful target for 1 Hz rTMS to modulate tic symptoms in GTS patients.

Supplementation of the maternal diet with Brazil nut (Bertholletia excelsa H.B.K.) prevents cognitive impairment in the offspring of obese mothers.

Maternal obesity may trigger long-term neurodevelopmental disorders in offspring. Considering the benefits of the Brazil nut (Bertholletia excelsa H.B.K.), a rich source of nutrients such as selenium, this study aimed to evaluate its effect on the behavior of obese rat offspring and its relationship with oxidative stress. From 60 days of age until weaning, female Wistar rats were fed a high-fat diet (mHF) or an HF diet supplemented with 5% Brazil nut (mHF/BN), while control mothers (mCTL) were fed a standard diet or a standard diet supplemented with 5% Brazil nut (mBN). Male pups received a standard diet throughout life and, at 30 and 90 days old, were subjected to behavioral tasks to evaluate anxiety and cognition. Biochemical evaluations were performed at 90 days of age. No alterations were observed in the anxiety behavior of the offspring. However, the offspring of the mHF group (oHF) exhibited impaired short-term memory at 30 and 90 days of age and impaired long-term memory at 30 days. Short-term memory impairment was prevented by Brazil nuts in young rats (30 days). While the serum selenium concentration was reduced in the oHF group, the serum catalase concentration was reduced in all groups, without changes in lipid peroxidation or protein carbonylation. Brazil nut maternal diet supplementation prevented short- and long-term cognitive impairment in the offspring, which may be related to the selenium levels.

[iOCT in clinical use : Correlation of intraoperative morphology and postoperative visual outcome in patients with full thickness macular hole]. / iOCT in der klinischen Anwendung : Korrelation von intraoperativer Morphologie und postoperativem Ergebnis bei Patienten mit durchgreifendem Makulaforamen.

BACKGROUND: Due to intraoperative optical coherence tomography (iOCT), observation of retinal morphological changes during surgery has become possible. OBJECTIVE: To analyze the intraoperative morphology of full thickness macular holes (FTMH) and the correlation with the postoperative function, a retrospective, observational clinical study was performed analyzing 32 eyes of patients treated at the hospital of the technical university of Munich. MATERIAL AND METHODS: Using iOCT in 32 eyes of 32 consecutive patients, the operative morphology was analyzed during surgery. These findings were then correlated with the postoperative visual outcome. RESULTS: After posterior vitreous detachment (PVD) the macular hole index (MHI) decreased by -0.05 (p = 0.01) and the base diameter (BD) increased by +99.4 µm (SD = 197.8 µm; p = 0.04). Closure rate was 100% at the first visit after a mean time of 73 days and the postoperative best corrected visual acuity (BCVA) significantly improved (p < 0.05). There were significant correlations between intraoperative morphology and postoperative results indicating a relation between low MHI and better postoperative BCVA (SCC = 0.50; p = 0.02), large BD and better postoperative BCVA (SCC = 0.43; p = 0.05) and large aperture after PVD and higher improvement of BCVA (SCC = 0.44; p = 0.03). CONCLUSION: Flattening and broadening of the FTMH occurred as a result of reduction of vitreoretinal traction. The significant correlation between a large operative BD and improved BCVA reveals the importance of intraoperative retinal relaxation.

The Effects of Different Theta and Beta Neurofeedback Training Protocols on Cognitive Control in ADHD.

Neurofeedback (NF) is an important treatment for attention deficit/hyperactivity disorder (ADHD). In ADHD, cognitive control deficits pose considerable problems to patients. However, NF protocols are not yet optimized to enhance cognitive control alongside with clinical symptoms, partly because they are not driven by basic cognitive neuroscience. In this study, we evaluated different EEG theta and/or beta frequency band NF protocols designed to enhance cognitive control. Participants were n = 157 children and adolescents, n = 129 of them were patients with ADHD (n = 28 typically developing (TD) controls). Patients with ADHD were divided into five groups in the order of referral, with four of them taking part in different NF protocols systematically varying theta and beta power. The fifth ADHD group and the TD group did not undergo NF. All NF protocols resulted in reductions of ADHD symptoms. Importantly, only when beta frequencies were enhanced during NF (without any theta regulation or in combination with theta upregulation), consistent enhancing effects in both response inhibition and conflict control were achieved. The theta/beta NF protocol most widely used in clinical settings revealed comparatively limited effects. Enhancements in beta band activity are key when aiming to improve cognitive control functions in ADHD. This calls for a change in the use of theta/beta NF protocols and shows that protocols differing from the current clinical standard are effective in enhancing important facets of cognitive control in ADHD. Further studies need to examine regulation data within the neurofeedback sessions to provide more information about the mechanisms underlying the observed effects. Supplementary Information: The online version contains supplementary material available at 10.1007/s41465-022-00255-6.

Urge-tic associations in children and adolescents with Tourette syndrome.

Premonitory urges preceding tics are a cardinal feature of Gilles de la Tourette syndrome (GTS), a developmental disorder usually starting during middle childhood. However, the temporal relation between urges and tics has only been investigated in adults. In 25 children and adolescents with GTS (8-18 years), we assess urge-tic associations, including inter-individual differences, correlation to clinical measures, and in comparison to a previously reported sample of adult GTS patients. Group-level analyses confirmed positive associations between urges and tics. However, at the individual level, less than half of participants showed positive associations, a similar proportion did not, and in two participants, the association was reversed. Tic expression and subjective urge levels correlated with corresponding clinical scores and participants with more severe tics during the urge monitor exhibited stronger urge-tic associations. Associations between reported urge levels and instantaneous tic intensity tended to be less pronounced in children and adolescents than in adult GTS patients. The observed heterogeneity of urge-tic associations cast doubt on the notion that tics are directly caused by urges. More severe tics may facilitate anticipation of tics and thereby lead to more pronounced urge-tic associations, consistent with a hypothesis of urges as a byproduct of tics.

Carbonic anhydrase IX overexpression is associated with diminished prognosis in esophageal cancer and correlates with Her-2 expression.

BACKGROUND: Carbonic anhydrase IX (CAIX), a transmembrane glycoprotein, seems to play a key role in the adaption of tumor cells to hypoxia. This study was designed to investigate the clinical role of CAIX and its association with Her-2 in a large cohort of adeno- (AC) and squamous cell carcinomas (SCC) of the esophagus and their metastases. METHODS: Expression of CAIX and Her-2 was investigated immunohistochemically in formalin fixed, paraffin-embedded tissue from 330 esophageal cancers (182 ACS, 148 SCCs). Corresponding lymph node metastases in 137 cases, distant metastases in 34 cases, and local recurrences in 14 cases were analyzed for CAIX expression. RESULTS: A total of 147 cases (44.5%) showed strong CAIX expression (AC: 46.7%; ACC: 41.9%). CAIX status of the primary tumor influenced CAIX expression in corresponding lymph node metastases (P<0.001, linear regression). High CAIX-expression was an independent prognostic factor for shorter overall and disease-free survival (P≤0.05, Cox regression). Twenty-nine ACs (15.9%) and 6 SCCs (4.1%) showed Her-2 overexpression. In AC, a significant positive correlation between the Her-2 status and CAIX expression was found (P=0.009, chi-square test). CONCLUSIONS: High CAIX expression is associated with shorter survival in esophageal cancer, and the hypoxic phenotype seems to be preserved at least during formation of lymph node metastases. Inhibition of CAIX might reduce the ability of tumor cells to establish disseminated disease. In Her-2 overexpressing ACs, blocking of this tyrosine kinase, e.g., by monoclonal antibodies, might induce this effect.

Somatosensory perception-action binding in Tourette syndrome.

It is a common phenomenon that somatosensory sensations can trigger actions to alleviate experienced tension. Such "urges" are particularly relevant in patients with Gilles de la Tourette (GTS) syndrome since they often precede tics, the cardinal feature of this common neurodevelopmental disorder. Altered sensorimotor integration processes in GTS as well as evidence for increased binding of stimulus- and response-related features ("hyper-binding") in the visual domain suggest enhanced perception-action binding also in the somatosensory modality. In the current study, the Theory of Event Coding (TEC) was used as an overarching cognitive framework to examine somatosensory-motor binding. For this purpose, a somatosensory-motor version of a task measuring stimulus-response binding (S-R task) was tested using electro-tactile stimuli. Contrary to the main hypothesis, there were no group differences in binding effects between GTS patients and healthy controls in the somatosensory-motor paradigm. Behavioral data did not indicate differences in binding between examined groups. These data can be interpreted such that a compensatory "downregulation" of increased somatosensory stimulus saliency, e.g., due to the occurrence of somatosensory urges and hypersensitivity to external stimuli, results in reduced binding with associated motor output, which brings binding to a "normal" level. Therefore, "hyper-binding" in GTS seems to be modality-specific.

Low and high stimulation frequencies differentially affect automated response selection in the superior parietal cortex - implications for somatosensory area processes.

Response inhibition as a central facet of executive functioning is no homogeneous construct. Interference inhibition constitutes a subcomponent of response inhibition and refers to inhibitory control over responses that are automatically triggered by irrelevant stimulus dimensions as measured by the Simon task. While there is evidence that the area-specific modulation of tactile information affects the act of action withholding, effects in the context of interference inhibition remain elusive. We conducted a tactile version of the Simon task with stimuli designed to be predominantly processed in the primary (40 Hz) or secondary (150 Hz) somatosensory cortex. On the basis of EEG recordings, we performed signal decomposition and source localization. Behavioral results reveal that response execution is more efficient when sensory information is mainly processed via SII, compared to SI sensory areas during non-conflicting trials. When accounting for intermingled coding levels by temporally decomposing EEG data, the results show that experimental variations depending on sensory area-specific processing differences specifically affect motor and not sensory processes. Modulations of motor-related processes are linked to activation differences in the superior parietal cortex (BA7). It is concluded that the SII cortical area supporting cognitive preprocessing of tactile input fosters automatic tactile information processing by facilitating stimulus-response mapping in posterior parietal regions.