Anke Hammer

Pramipexole modulates the neural network of reward anticipation

Pramipexole is widely prescribed to treat Parkinsons 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.

Pronominal Reference in Sentences about Persons or Things: An Electrophysiological Approach

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.

Observation of sonified movements engages a basal ganglia frontocortical network.

BackgroundProducing 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.ResultsHere 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.ConclusionsWe 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.

Interplay of meaning, syntax and working memory during pronoun resolution investigated by ERPs.

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.

Neural correlates of semantic and syntactic processes in the comprehension of case marked pronouns: Evidence from German and Dutch

BackgroundIt 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.ResultsThe 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.ConclusionFinding 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.

Brain Potentials of Conflict and Error-Likelihood Following Errorful and Errorless Learning in Obsessive-Compulsive Disorder

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.

A neurophysiological analysis of working memory in amyotrophic lateral sclerosis.

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.

When sex meets syntactic gender on a neural basis during pronoun processing.

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 Brocas 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.

Differences in the processing of anaphoric reference between closely related languages: neurophysiological evidence

BackgroundThe 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.ResultsIn 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.ConclusionThe 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).

Neural mechanisms of anaphoric reference revealed by FMRI.

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 (incongruentu2009>u2009congruent) and Distance (longu2009>u2009short). 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).