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Weitere Nicht-UDE Autoren sind nicht genannt. Importance: The behavioral and cognitive symptoms of severe psychotic disorders overlap with those seen in dementia. However, shared brain alterations remain disputed, and their relevance for patients in at-risk disease stages has not been explored so far. Objective: To use machine learning to compare the expression of structural magnetic resonance imaging (MRI) patterns of behavioral-variant frontotemporal dementia (bvFTD), Alzheimer disease (AD), and schizophrenia; estimate predictability in patients with bvFTD and schizophrenia based on sociodemographic, clinical, and biological data; and examine prognostic value, genetic underpinnings, and progression in patients with clinical high-risk (CHR) states for psychosis or recent-onset depression (ROD). Design, Setting, and Participants: This study included 1870 individuals from 5 cohorts, including (1) patients with bvFTD (n = 108), established AD (n = 44), mild cognitive impairment or early-stage AD (n = 96), schizophrenia (n = 157), or major depression (n = 102) to derive and compare diagnostic patterns and (2) patients with CHR (n = 160) or ROD (n = 161) to test patterns' prognostic relevance and progression. Healthy individuals (n = 1042) were used for age-related and cohort-related data calibration. Data were collected from January 1996 to July 2019 and analyzed between April 2020 and April 2022. Main Outcomes and Measures: Case assignments based on diagnostic patterns; sociodemographic, clinical, and biological data; 2-year functional outcomes and genetic separability of patients with CHR and ROD with high vs low pattern expression; and pattern progression from baseline to follow-up MRI scans in patients with nonrecovery vs preserved recovery. Results: Of 1870 included patients, 902 (48.2%) were female, and the mean (SD) age was 38.0 (19.3) years. The bvFTD pattern comprising prefrontal, insular, and limbic volume reductions was more expressed in patients with schizophrenia (65 of 157 [41.2%]) and major depression (22 of 102 [21.6%]) than the temporo-limbic AD patterns (28 of 157 [17.8%] and 3 of 102 [2.9%], respectively). bvFTD expression was predicted by high body mass index, psychomotor slowing, affective disinhibition, and paranoid ideation (R2= 0.11). The schizophrenia pattern was expressed in 92 of 108 patients (85.5%) with bvFTD and was linked to the C9orf72 variant, oligoclonal banding in the cerebrospinal fluid, cognitive impairment, and younger age (R2= 0.29). bvFTD and schizophrenia pattern expressions forecasted 2-year psychosocial impairments in patients with CHR and were predicted by polygenic risk scores for frontotemporal dementia, AD, and schizophrenia. Findings were not associated with AD or accelerated brain aging. Finally, 1-year bvFTD/schizophrenia pattern progression distinguished patients with nonrecovery from those with preserved recovery. Conclusions and Relevance: Neurobiological links may exist between bvFTD and psychosis focusing on prefrontal and salience system alterations. Further transdiagnostic investigations are needed to identify shared pathophysiological processes underlying the neuroanatomical interface between the 2 disease spectra.

The steepness of the delay discounting function shows considerable interindividual differences. Moreover, faster devaluation of future rewards has been consistently observed in pathological gamblers (PGs). Here, we asked whether variability in delay discounting is at least partially driven by differences in the anatomy of gray and white matter. For 40 healthy young subjects (study 1) as well as 15 PG and 15 age-matched healthy controls (HCs, study 2), the individual discounting parameter k was obtained. Based on 3D T1-weighted high-resolution magnetic resonance scans and diffusion tensor imaging, we performed voxel-based morphometry and tract-based spatial statistics, respectively, to examine the relation of gray matter volume (GMV) and white matter properties (as indicated by fractional anisotropy, FA) to k. Healthy groups from both studies showed a negative correlation between k and FA for the superior longitudinal fascicle and inferior longitudinal fascicle, whereas a positive correlation was found in the PG group for the inferior longitudinal fascicle and left inferior fronto-occipital fascicle. The latter also was significantly different between HC and PG in the group statistics (albeit on the right side), thus suggesting that this is a significant structure for the development of pathological gambling. GMV of the right frontal orbital cortex, left insular cortex and right lateral occipital cortex showed a positive correlation to k HC (studies 1 and 2) and PG, whereas a negative correlation was found for the left frontal pole in all three groups. Group comparison of GMV (study 2) revealed a decrease in PG for several cortical and subcortical areas.

Pramipexole is widely prescribed to treat Parkinson's disease but has been reported to cause impulse control disorders such as pathological gambling. Recent neurocomputational models suggested that D2 agonists may distort functional connections between the striatum and the motor cortex, resulting in impaired reinforcement learning and pathological gambling. To examine how D2 agonists modulate the striatal-motor connectivity, we carried out a pharmacological resting-state functional magnetic resonance imaging study with a double-blind randomized within-subject crossover design. We analyzed the medication-induced changes of network connectivity and topology with two approaches, an independent component analysis (ICA) and a graph theoretical analysis (GTA). The ICA identified the sensorimotor network (SMN) as well as other classical resting-state networks. Within the SMN, the connectivity between the right caudate nucleus and other cortical regions was weaker under pramipexole than under placebo. The GTA measured the topological properties of the whole-brain network at global and regional levels. Both the whole-brain network under placebo and that under pramipexole were identified as small-world networks. The two whole-brain networks were similar in global efficiency, clustering coefficient, small-world index, and modularity. However, the degree of the right caudate nucleus decreased under pramipexole mainly due to the loss of the connectivity with the supplementary motor area, paracentral lobule, and precentral and postcentral gyrus of the SMN. The two network analyses consistently revealed that pramipexole weakened the functional connectivity between the caudate nucleus and the SMN regions.

The error-likelihood model (ELM) postulates that activity of the anterior cingulate cortex is not only modulated by the commitment of an error but is rather dependent on the perceived ELM within task context. In this event-related potential (ERP) study we challenge these assumptions with a word-recognition paradigm. While learning phases were constant, ELM was modulated during recognition by varying the ratio of old and new words: old and new words had the same probability in low-risk sessions and the number of new words was tripled in high-risk sessions. Response-locked ERPs of correct yes-responses compared to no-responses revealed two different components with fronto-central distributions. The first negativity (time-range of the error-related negativity) elicited differentiations between yes- and no-responses. Yes-responses in high-risk compared to low-risk sessions resulted in an enlarged negativity. These results support the ELM which states that the activation of the anterior cingulate cortex is also modulated by the participant's perceived likelihood to commit an error and not the correctness of the response per se.

Pramipexole is widely prescribed to treat Parkinson's disease. It has been found to cause impulse control disorders such as pathological gambling. To examine how pramipexole modulates the network of reward anticipation, we carried out a pharmacological functional magnetic resonance imaging study with a double‐blind, within‐subject design. During the anticipation of monetary rewards, pramipexole increased the activity of the nucleus accumbens (NAcc), enhanced the interaction between the NAcc and the anterior insula, but weakened the interaction between the NAcc and the prefrontal cortex. These results suggest that pramipexole may exaggerate incentive and affective responses to possible rewards, but reduce the top‐down control of impulses, leading to an increase in impulsive behaviors. This imbalance between the prefrontal‐striatum connectivity and the insula‐striatum connectivity may represent the neural mechanism of pathological gambling caused by pramipexole. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.

Event-related potentials were used to investigate the interaction of verbal working memory and gender information during pronoun resolution. Gender information is supposed to be disentangled using sentences about persons (semantic/syntactic) or things (syntactic) followed by gender congruent or incongruent pronouns. Memory was manipulated using differential distances (short distance (SD) and long distances with or without intermediate subject gaps (LD gap and LD no gap)) between the pronoun and the antecedent. Comparing incongruent to congruent conditions, person sentences with SD and LD no gap resulted in an N400-like effect indicating the involvement of semantic integration, whereas a P600 effect in LD gap (re-activated antecedents) sentences suggested the involvement of syntactic reanalysis. SD-thing sentences showed a P600 effect, whereas LD thing sentences revealed no effect at pronoun position. A delayed N400 effect for thing sentences was observed instead. Based on preceding and the current data, we present a working model on how the parser switches between the use of semantic and syntactic information to establish co-reference and how this switch depends on the type of antecedent, distance, or syntactic structure.

Liver X receptor (LXR) agonists have been proposed to act as anti-diabetic drugs. However, pharmacological LXR activation leads to severe hepatic steatosis, a condition usually associated with insulin resistance and type 2 diabetes mellitus. To address this apparent contradiction, lean and ob/ob mice were treated with the LXR agonist GW-3965 for 10 days. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp studies. Hepatic glucose production (HGP) and metabolic clearance rate (MCR) of glucose were determined with stable isotope techniques. Blood glucose and hepatic and whole body insulin sensitivity remained unaffected upon treatment in lean mice, despite increased hepatic triglyceride contents (61.7 ± 7.2 vs. 12.1 ± 2.0 nmol/mg liver, P < 0.05). In ob/ob mice, LXR activation resulted in lower blood glucose levels and significantly improved whole body insulin sensitivity. GW-3965 treatment did not affect HGP under normo- and hyperinsulinemic conditions, despite increased hepatic triglyceride contents (221 ± 13 vs. 176 ± 19 nmol/mg liver, P < 0.05). Clamped MCR increased upon GW-3965 treatment (18.2 ± 1.0 vs. 14.3 ± 1.4 ml·kg−1·min−1, P = 0.05). LXR activation increased white adipose tissue mRNA levels of Glut4, Acc1 and Fasin ob/ob mice only. In conclusion, LXR-induced blood glucose lowering in ob/ob mice was attributable to increased peripheral glucose uptake and metabolism, physiologically reflected in a slightly improved insulin sensitivity. Remarkably, steatosis associated with LXR activation did not affect hepatic insulin sensitivity.

Contains fulltext : 42649-OA.pdf (Publisher’s version ) (Open Access) German pronouns (erMALE/masculine, sieFEMALE/feminine) that refer to a person are determined by the biological gender (MALE/FEMALE) and/or syntactic gender (masculine/feminine) of the person. Pronouns (ermasculine, siefeminine) that refer to a thing are determined by the syntactic gender of this thing (Garten [garden]masculine, Tasche [hand-bag]feminine). The study aimed to investigate whether semantic integration, syntactic integration, or both are involved in establishing co-reference between pronoun and subject/antecedent in sentences. Here we focused on two event-related potential components: the SPS/P600, related to syntactic violation and reanalysis, and the N400 component, related to semantic integration problems. In one condition, a person was introduced as antecedent and later referred to by a pronoun, which either agreed in biological/syntactic gender or not (biological/syntactic gender violation). In a second condition, a thing was introduced as antecedent and the corresponding pronoun either agreed in syntactic gender or not (syntactic gender violation). Results at critical pronouns showed a P600 effect for incongruent compared with congruent pronouns in both conditions with a centro-parietal maximum. This effect was larger for the person compared to the thing condition. We interpreted this finding as reflecting a syntactic integration process that can be influenced by conceptual/semantic and syntactic information of the antecedent type. Furthermore, at the word following the pronoun, we observed an N400 for the thing but not for the person condition. We suggest, supported by the results of a control experiment, that this effect reflects continuous integration processes for things, whereas for persons the integration seems to be finished at pronoun position. 13 p.

Background Brands create product personalities that are thought to affect consumer decisions. Here we assessed, using the Go/No-go Association Task (GNAT) from social psychology, whether brands as opposed to no-name products are associated with implicit positive attitudes. Healthy young German participants viewed series of photos of cosmetics and food items (half of them brands) intermixed with positive and negative words. In any given run, one category of goods (e.g., cosmetics) and one kind of words (e.g., positive) had to be responded to, whereas responses had to be withheld for the other categories. Event-related brain potentials were recorded during the task. Results Unexpectedly, there were no response-time differences between congruent (brand and positive words) and incongruent (brand and negative words) pairings but ERPs showed differences as a function of congruency in the 600–750 ms time-window hinting at the existence of implicit attitudes towards brand and no-name stimuli. This finding deserves further investigation in future studies. Moreover, the amplitude of the late positive component (LPC) was found to be enhanced for brand as opposed to no-name stimuli. Conclusions Congruency effects suggest that ERPs are sensitive to implicit attitudes. Moreover, the results for the LPC imply that pictures of brand products are more arousing than those of no-name products, which may ultimately contribute to consumer decisions.

Background Errorless learning has advantages over errorful learning. The erroneous items produced during errorful learning compete with correct items at retrieval resulting in decreased memory performance. This interference is associated with an increased demand on executive monitoring processes. Event-related functional magnetic resonance imaging (fMRI) was used to contrast errorless and errorful learning. Learning mode was manipulated by the number of distractors during learning of face-name associations: in errorless learning only the correct name was introduced. During errorful learning either one incorrect name or two incorrect names were additionally introduced in order to modulate the interference in recognition. Results The behavioural results showed an enhanced memory performance after errorless learning. The veridicality of recognition of the face-name associations was reflected in a left lateralized fronto-temporal-parietal network. The different learning modes were associated with modulations in left prefrontal and parietal regions. Conclusions Errorless learning enhances memory performance as compared to errorful learning and underpins the known advantages for errorless learning. During memory retrieval different networks are engaged for specific purposes: Recognition of face-name associations engaged a lateralized fronto-temporal-parietal network and executive monitoring processes of memory engaged the left prefrontal and parietal regions.

Background Producing sounds by a musical instrument can lead to audiomotor coupling, i.e. the joint activation of the auditory and motor system, even when only one modality is probed. The sonification of otherwise mute movements by sounds based on kinematic parameters of the movement has been shown to improve motor performance and perception of movements. Results Here we demonstrate in a group of healthy young non-athletes that congruently (sounds match visual movement kinematics) vs. incongruently (no match) sonified breaststroke movements of a human avatar lead to better perceptual judgement of small differences in movement velocity. Moreover, functional magnetic resonance imaging revealed enhanced activity in superior and medial posterior temporal regions including the superior temporal sulcus, known as an important multisensory integration site, as well as the insula bilaterally and the precentral gyrus on the right side. Functional connectivity analysis revealed pronounced connectivity of the STS with the basal ganglia and thalamus as well as frontal motor regions for the congruent stimuli. This was not seen to the same extent for the incongruent stimuli. Conclusions We conclude that sonification of movements amplifies the activity of the human action observation system including subcortical structures of the motor loop. Sonification may thus be an important method to enhance training and therapy effects in sports science and neurological rehabilitation.

The advantage of errorless learning over errorful learning is associated with the avoidance of errors during learning. Errorful learning challenges the executive control system as erroneous items compete with correct items during retrieval. In an event-related potential (ERP) study, face-name associations learned in errorless or errorful mode were contrasted during retrieval. Learning mode was manipulated by the number of distracters. This modulation resulted in best performances after errorless learning followed by medium and high conflict errorful learning but lost its advantage over time. Within stimulus-locked ERPs, the N250 and the N400f components were associated with successful retrieval. The N250 was also driven by learning mode. Within response-locked ERPs, the error-related negativity (ERN) was modulated by correctness. The error-positivity (Pe) to erroneous responses was modulated by learning mode. The study reveals an initial advantage of errorless over errorful learning, which diminishes over time. The neurocognitive findings are discussed in light of conflict and error-likelihood models.

Background Errorless learning is advantageous over trial and error learning (errorful learning) as errors are avoided during learning resulting in increased memory performance. Errorful learning challenges the executive control system of memory processes as the erroneous items compete with the correct items during retrieval. The left dorsolateral prefrontal cortex (DLPFC) is a core region involved in this executive control system. Transcranial direct current stimulation (tDCS) can modify the excitability of underlying brain functioning. Results In a single blinded tDCS study one group of young healthy participants received anodal and another group cathodal tDCS of the left DLPFC each compared to sham stimulation. Participants had to learn words in an errorless and an errorful manner using a word stem completion paradigm. The results showed that errorless compared to errorful learning had a profound effect on the memory performance in terms of quality. Anodal stimulation of the left DLPFC did not modulate the memory performance following errorless or errorful learning. By contrast, cathodal stimulation hampered memory performance after errorful learning compared to sham, whereas there was no modulation after errorless learning. Conclusions Concluding, the study further supports the advantages of errorless learning over errorful learning. Moreover, cathodal stimulation of the left DLPFC hampered memory performance following the conflict-inducing errorful learning as compared to no modulation after errorless learning emphasizing the importance of the left DLPFC in executive control of memory.

Frontal lobe functions, in particular working memory (WM) and verbal fluency, have been found to be deficient in amyotrophic lateral sclerosis (ALS). To study the neural correlates of WM-impairment, ALS patients and healthy age-matched controls were subjected to two working memory tasks following the 2-back paradigm, one requiring the storage of figural information, the other storage of spatial information. A significant proportion of ALS patients were unable to perform the WM-tasks. Those who could showed worse performance in the spatial task than the controls. Event-related brain potentials recorded during the task revealed a topographical change of the working memory effect in the ALS patients. Thus, behavioral and electrophysiological data suggest an alteration of working memory, in particular for spatial information, in ALS. Additionally, the patients also took part in two Go/Nogo tasks (spatial, figural) using the same stimulus material but defining targets prior to the experiment instead of a working memory manipulation. Here, an anteriorization of the nogo-P3 was found which has been established as an index of impaired inhibitory functions.

Pronouns are bound to their antecedents by matching syntactic and semantic information. The aim of this functional magnetic resonance imaging study was to localize syntactic and semantic information retrieval and integration during pronoun resolution. Especially we investigated their possible interaction with verbal working memory manipulated by distance between antecedent and pronoun. We disentangled biological and syntactic gender information using German sentences about persons (biological/syntactic gender) or things (syntactic gender) followed by congruent or incongruent pronouns. Increasing the distance between pronoun and antecedent resulted in a short and a long distance condition. Analysis revealed a language related network including inferior frontal regions bilaterally (integration), left anterior and posterior temporal regions (lexico-semantics and syntactic retrieval) and the anterior cingulate gyrus (conflict resolution) involved in pronoun resolution. Activities within the inferior frontal region were driven by Congruency (incongruent>congruent) and Distance (long>short). Temporal regions were sensitive to Distance and Congruency (but solely within long distant conditions). Furthermore, anterior temporal regions were sensitive to the antecedent type with an increased activity for person pronouns compared to thing pronouns. We suggest that activity modulations within these areas reflect the integration process of an appropriate antecedent which depends on the type of information that has to be retrieved (lexico-syntactic posterior temporal, lexico-semantics anterior temporal). It also depends on the overall syntactic and semantic complexity of long distant sentences. The results are interpreted in the context of the memory-unification-control model for sentence comprehension as proposed by Vosse and Kempen (2000), Hagoort (2005), and Snijders et al. (2009).

Amyotrophic lateral sclerosis (ALS) features central and peripheral paresis owing to the degeneration of upper and lower motor neurons. Here, we asked whether motor preparation and inhibition are also affected. Thirteen ALS patients and thirteen matched controls participated in an event-related brain potentials (ERP) experiment in which a cue stimulus indicated whether the following target stimulus was to be responded to by the left or the right hand by a speeded button press. In 25% of the trials a stop-signal followed the target stimulus (onset asynchrony 150 ms) indicating that participants had to abort the already initiated motor response. ERPs indicated deficits of the ALS patients in the preparation and inhibition of motor responses: The lateralized readiness potential indicating motor preparation had a grossly reduced amplitude. A right frontal negative component following about 200 ms after the stop-signal and known to indicate inhibitory processes was diminished in amplitude and prolonged in latency in ALS. Finally, a later negative component associated with error processing was also reduced in amplitude in ALS. These electrophysiological changes were accompanied by behavioral deficits in the patient group (less efficient stopping of movements, no reaction time adaptation after stop trials). In conclusion, ALS patients showed deficits in both, movement initiation and inhibition, with the latter associated with prefrontal dysfunction.

We used event-related functional magnetic resonance imaging (erfMRI) to investigate the neural basis of biological and syntactic gender integration during pronoun processing in German sentences about persons or things. German allows for separating both processes experimentally. Overall, syntactic processing activated areas adjacent to Broca's area (BA 44), whereas processing of the biological sex, in addition, involved the supramarginal gyrus (BA 39). A previously reported event-related potential study using identical material suggests that syntactic and semantic information is integrated 400-700 ms after target onset, visible in both cases as a P600 but with different effect sizes. The fMRI and ERP results illuminate that pronoun processing involves a highly dynamic spatiotemporal integration of syntactic and biological information depending on the type of the antecedent and whether or not a violation is involved. The results are discussed in the context of cognitive models of pronoun processing.

Background It is well known that both semantic and syntactic information play a role in pronoun resolution in sentences. However, it is unclear what the relative contribution of these sources of information is for the establishment of a coreferential relationship between the pronoun and the antecedent in combination with a local structural case constraint on the pronoun (i.e. case assignment of a pronoun under preposition governing). In a prepositional phrase in German and Dutch, it is the preposition that assigns case to the pronoun. Furthermore, in these languages different overtly case-marked pronouns are used to refer to male and female persons. Thus, one can manipulate biological/syntactic gender features separately from case marking features. The major aim of this study was to determine what the influence of gender information in combination with a local structural case constraint is on the processing of a personal pronoun in a sentence. Event-related brain potential (ERP) experiments were performed in German and in Dutch. In a word by word sentence reading study in German and Dutch, gender congruency between the antecedent and the pronoun was manipulated and/or case assignment by the preposition was violated while ERPs of young native speakers were recorded. Results The German and the Dutch ERP data showed an enlarged negativity broadly distributed starting approximately 350 ms after onset of the pronoun followed by a late positivity for gender violations. For syntactic incongruencies without gender violations only a positivity was present. The Dutch data showed an earlier onset of the positivity in comparison to German. Conclusion Finding negativities and positivities for conditions with a gender violation indicates that pronoun resolution with gender incongruency between the pronoun and the antecedent suffers from semantic as well as syntactic integration problems. The presence of a positivity for the syntactically incongruent conditions without gender violations suggests that the processing of incorrect case marking without a gender violation gives rise to syntactic but not semantic integration problems. We suggest that the more prominent case violation in Dutch caused the earlier onset of the positivity in the Dutch study. In addition, the pattern of ERP effects shows that both case and gender information are used almost immediately implying that the local structural constraint affects the resolution process with more processing activity than for a pronoun of which only one source of information is violated or incongruent.

Background The anterior cingulate cortex (ACC) is thought to be overacting in patients with Obsessive Compulsive Disorder (OCD) reflecting an enhanced action monitoring system. However, influences of conflict and error-likelihood have not been explored. Here, the error-related negativity (ERN) originating in ACC served as a measure of conflict and error-likelihood during memory recognition following different learning modes. Errorless learning prevents the generation of false memory candidates and has been shown to be superior to trial-and-error-learning. The latter, errorful learning, introduces false memory candidates which interfere with correct information in later recognition leading to enhanced conflict processing. Methodology/Principal Findings Sixteen OCD patients according to DSM-IV criteria and 16 closely matched healthy controls participated voluntarily in the event-related potential study. Both, OCD- and control group showed enhanced memory performance following errorless compared to errorful learning. Nevertheless, response-locked data showed clear modulations of the ERN amplitude. OCD patients compared to controls showed an increased error-likelihood effect after errorless learning. However, with increased conflict after errorful learning, OCD patients showed a reduced error-likelihood effect in contrast to controls who showed an increase. Conclusion/Significance The increase of the errorlikelihood effect for OCD patients within low conflict situations (recognition after errorless learning) might be conceptualized as a hyperactive monitoring system. However, within high conflict situations (recognition after EF-learning) the opposite effect was observed: whereas the control group showed an increased error-likelihood effect, the OCD group showed a reduction of the error-likelihood effect based on altered ACC learning rates in response to errors. These findings support theoretical frameworks explaining differences in ACC activity on the basis of conflict and perceived error-likelihood as influenced by individual error learning rate.

Background The present study examines the involvement of syntactic and semantic/conceptual processes in the comprehension of pronouns in Dutch using the technique of event-related brain potentials (ERPs) replicating and extending an earlier study in German. Dutch and German are closely related and share the same logic in referring to non-diminutive and diminutive NPs (i.e. adding an affix which changes the syntactic gender into neutral). Both languages separate male (hij/er (he)) and female pronouns (zij/sie (she)), as well as a pronoun that refers to an entity of neutral gender, (het/es (it)). However, the neutral pronoun het in Dutch is not only a pronoun, it also is the article of a neutral noun. To investigate the influence of this word class ambiguity on pronoun resolution, as well as to establish the generality of the finding of the German study we manipulated syntactic and biological gender congruency between a personal pronoun and its antecedent in Dutch. Results In Dutch, sentences with the word-class (pronoun/article) ambiguous pronoun het elicited an early negative shift (150–280 ms) which continued in the time frame of the N400. For sentences with a syntactically and biologically incongruent pronoun a P600 (in absence of an N400) was obtained, which was independent of the morphological form of the referent. Conclusion The neurophysiological pattern found for Dutch stimuli was clearly different from the German study, indicating that the processing of pronouns in these two languages differs. This can be explained in terms of language specific characteristics concerning the word class ambiguous neutral pronoun het. Moreover, in contrast to the findings in the German study, there was no clear effect caused by the morphological form of the referent. Additionally, in Dutch, the pronoun resolution in sentences with a non-diminutive antecedent seems to reflect processes of revision (P600 in absence of an N400), whereas for German evidence was found for clear involvement of conceptual/semantic processes as well as structure building processes (N400/P600 complex).